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Clinical Guidelines
9 April 2019

Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of PhysiciansFREE

This article has been corrected.
VIEW CORRECTION
Publication: Annals of Internal Medicine
Volume 170, Number 8

Abstract

Description:

The purpose of this guidance statement is to provide advice to clinicians on breast cancer screening in average-risk women based on a review of existing guidelines and the evidence they include.

Methods:

This guidance statement is derived from an appraisal of selected guidelines from around the world that address breast cancer screening, as well as their included evidence. All national guidelines published in English between 1 January 2013 and 15 November 2017 in the National Guideline Clearinghouse or Guidelines International Network library were included. In addition, the authors selected other guidelines commonly used in clinical practice. Web sites associated with all selected guidelines were checked for updates on 10 December 2018. The AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument was used to evaluate the quality of guidelines.

Target Audience and Patient Population:

The target audience is all clinicians, and the target patient population is all asymptomatic women with average risk for breast cancer.

Guidance Statement 1:

In average-risk women aged 40 to 49 years, clinicians should discuss whether to screen for breast cancer with mammography before age 50 years. Discussion should include the potential benefits and harms and a woman's preferences. The potential harms outweigh the benefits in most women aged 40 to 49 years.

Guidance Statement 2:

In average-risk women aged 50 to 74 years, clinicians should offer screening for breast cancer with biennial mammography.

Guidance Statement 3:

In average-risk women aged 75 years or older or in women with a life expectancy of 10 years or less, clinicians should discontinue screening for breast cancer.

Guidance Statement 4:

In average-risk women of all ages, clinicians should not use clinical breast examination to screen for breast cancer.
Breast cancer is the most common cancer type in women and the fourth leading cause of cancer death in the United States (1). The goal of screening is to reduce morbidity and mortality, both specific to breast cancer and overall, with acceptable tradeoffs (2, 3). The most commonly used screening test is mammography. Recommended strategies vary for breast cancer screening in average-risk women. Ages to start and discontinue mammography, screening intervals, the role of imaging methods other than mammography, and the role of clinical breast examination (CBE) have been points of disagreement among guideline developers.

Purpose and Target Population

The goal of this American College of Physicians (ACP) guidance statement is to critically review selected guidelines from around the world and their included evidence to assist clinicians in making decisions about breast cancer screening in asymptomatic women with average risk for breast cancer. Included screening methods are CBE and breast imaging (that is, mammography, ultrasonography, magnetic resonance imaging [MRI], and digital breast tomosynthesis [DBT]). This guidance statement does not address breast self-examination because no evaluated guideline recommends it for screening.
The target population for this guidance statement is women with average risk for breast cancer. The target audience is all clinicians.
Age is the single most important risk factor for breast cancer. Included guidelines generally define average-risk women as those who do not have a personal history of breast cancer or a previous diagnosis of a high-risk breast lesion, are not at high risk for breast cancer due to genetic mutations known to increase that risk (such as BRCA1/2 gene mutation or another familial breast cancer syndrome), and were not exposed to radiation therapy to the chest in childhood (4, 5). However, definitions of average risk vary among guidelines. In addition, although risk factors (including early menarche, late menopausal onset, oral contraceptive or menopausal hormone therapy, increased breast density on mammography, and a family member with a history of postmenopausal breast cancer) may put a woman at greater risk for breast cancer than women without these factors, the evaluated guidelines generally include women with these factors under the umbrella of average risk. Therefore, our guidance statement applies to these women.
Guidelines vary somewhat in target populations and screening methods addressed (Table [4–11] and Appendix). Both the U.S. Preventive Services Task Force (USPSTF) and the World Health Organization (WHO) include women with dense breasts and those with a single family member with breast cancer in their guideline's target population (5, 6). The Canadian Task Force on Preventive Health Care (CTFPHC) guideline also includes women with dense breasts; however, it explicitly mentions that women with a first-degree relative with breast cancer are considered to be at increased risk and are thus excluded from the guideline (7).
Table. Summary of Included Recommendations in Assessed Guidelines for Breast Cancer Screening of Average-Risk Women
Table. Summary of Included Recommendations in Assessed Guidelines for Breast Cancer Screening of Average-Risk Women

Methods

The ACP Clinical Guidelines Committee develops guidance statements on topics where several conflicting guidelines are available. Guidance statements rely on evidence presented or referenced in selected guidelines and accompanying evidence reports; they do not include de novo reviews or searches of the literature outside the body of evidence referenced by the guidelines. The goal of ACP guidance statements is to provide clinicians with a rigorous review of the available guidelines and their included evidence and to develop subsequent guidance based on an assessment of the benefits and harms reported by each guideline and its evidence. Unlike ACP guidelines, guidance statements are not derived from a systematic evidence review and hence do not use GRADE (Grading of Recommendations Assessment, Development and Evaluation) (12) to assess the quality of evidence or strength of recommendations.

Data Sources and Guideline Selection

We searched the National Guideline Clearinghouse and the Guidelines International Network library for breast cancer screening guidelines from national organizations that addressed breast imaging (that is, mammography, ultrasonography, MRI, or DBT) and CBE in women and were published in English between 1 January 2013 and 15 November 2017. We searched Web sites housing the selected guidelines for updates on 10 December 2018. We excluded guidelines that addressed specific populations (such as pregnant women and women at increased risk for breast cancer) or were more than 5 years old (thus considered inactive). We also excluded guidelines that directly endorsed another guideline, such as that of the American Academy of Family Physicians, which endorsed the USPSTF guideline. Our search yielded 3 guidelines, from the American College of Radiology (published in 2017; literature search end date, February 2016) (9), American Cancer Society (ACS) (published in 2015; literature search end date, March 2014) (4), and USPSTF (published in 2016; literature search end date, June 2015) (5). We also selected 3 guidelines not identified in either database but commonly used in clinical practice, from the National Comprehensive Cancer Network (NCCN) (published in 2018; literature search end date not reported) (10), WHO (published in 2014; literature search end date, December 2012) (6), and American College of Obstetricians and Gynecologists (published in 2017; literature search end date not applicable) (8). In addition, we selected the CTFPHC guideline, which was updated after our initial search (published in 2018; literature search end date, January 2017) (7). The American College of Obstetricians and Gynecologists guideline was based on guidelines from the ACS, NCCN, and USPSTF and supporting evidence reviews.

Critical Appraisal

Five coauthors independently reviewed, assessed, and scored each guideline using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument (13, 14) (Appendix Table 1).
Appendix Table 1. Scaled AGREE II Domain Scores for Each Guideline and Overall Assessment
Appendix Table 1. Scaled AGREE II Domain Scores for Each Guideline and Overall Assessment

Clinician Peer Review

The guidance statement was peer-reviewed through Annals of Internal Medicine and by ACP Regents and Governors, who represent ACP members at the regional and international level.

Public Member Review

The development process for the guidance statement included participation by public members (2 of the Clinical Guidelines Committee and 7 of ACP's Public Panel) to share their perspectives, values, and preferences.

Critical Appraisal of Evaluated Guidelines

The major difference between high- and low-scoring guidelines (Appendix Table 1) was methodology. Guidelines from ACS (4), CTFPHC (7), USPSTF (5), and WHO (6) scored highest on the AGREE II instrument, whereas those from the American College of Obstetricians and Gynecologists (8), American College of Radiology (9), and NCCN (10) scored lowest. In addition to our review of each guideline, we examined the evidence supporting the 4 that scored highest (ACS, CTFPHC, USPSTF, and WHO). We also considered recommendations for adoption or adaptation from these 4 guidelines when developing our own guidance.
Several factors were important in considering guideline quality. The ACS, CTFPHC, USPSTF, and WHO guidelines best articulated benefits, harms, and strength of the evidence and how these link to recommendations. The lower-scoring guidelines often inadequately described how they considered these factors in developing the recommendations, or they relied on lower-quality evidence. The guidelines varied in the studies they reported, weighting of observational or modeling studies relative to randomized controlled trials (RCTs), and emphasis on relative versus absolute effects. The guidelines rarely addressed the small absolute effect on breast cancer mortality; the long lead time to any reduction in this mortality, especially in women with estimated life expectancy less than 15 to 20 years; and the low incidence of breast cancer for women younger than 60 years.

Mammography

Depending on the guideline, the recommended age to discuss initiating screening is 40 years (4, 5, 8) and the recommended age to start screening ranges from 40 (9, 10) to 45 (4) to 50 (5–8) years. Most guidelines agree to screen average-risk women with mammography between ages 50 and 74 years. However, WHO and CTFPHC recommend that screening in women aged 50 to 69 years should include shared decision making because screening is conditional on a woman's values and preferences. For women aged 70 to 75 years, WHO recommends screening only in the context of both rigorous research and shared decision making. Other areas of disagreement include screening in women aged 40 to 49 years, screening in women aged 75 years or older, and recommended screening intervals (Table). Intervals range from annual (particularly in women aged 40 to 49 years) to biennial or triennial. Guidelines from ACS, USPSTF, and WHO conclude that a close balance exists between screening benefits and harms for women in their 40s (for ACS, 40 to 44 years) and that decisions are influenced by patient preferences. The WHO guideline suggests population-based screening programs in women aged 40 to 49 years only in the context of rigorous research, monitoring, and evaluation and if shared decision-making strategies are implemented. The CTFPHC conditionally recommends against screening in women aged 40 to 49 years (without a first-degree family history of breast cancer); however, it states that some women in this age group may wish to be screened and that clinicians should engage in shared decision making with women who express interest (Appendix).
Appendix Table 2 summarizes the available data from the 4 guidelines with the highest AGREE II scores (ACS, CTFPHC, USPSTF, and WHO).
Appendix Table 2. Summary of Evidence on Screening Mammography*
Appendix Table 2. Summary of Evidence on Screening Mammography*

Benefits

All-Cause Mortality

Individual studies were not designed to assess all-cause mortality. Pooled results from meta-analyses of RCTs demonstrated that mammography was not associated with a reduction in all-cause mortality (Appendix Table 2) (6, 15, 16).

Breast Cancer–Associated Mortality and Advanced Breast Cancer

Reductions in breast cancer–associated mortality differed by age group and study type (Appendix Table 2). Guideline developers assessed the same set of screening trials but used different methods for calculating absolute mortality reductions according to age and thus arrived at different results. The evidence reviews all showed a statistically significant reduction in relative risk for breast cancer mortality for women aged 50 to 69 years (6, 15–17). Only ACS and WHO found statistically significant results for ages 39 to 49 years (6, 17). The CTFPHC considered a single reduction in relative risk across all age groups for women aged 40 to 74 years, and thus only absolute risk differences varied across age groups in its review (16). All 4 evidence reviews showed that women aged 39 to 49 years derived the lowest absolute benefit in terms of deaths prevented (6, 15–17) (Appendix Table 2).
Observational studies showed larger relative reductions in breast cancer mortality (15). Evidence from RCTs (fair quality) and observational studies (poor quality) did not show a reduction in the incidence of advanced disease with breast cancer screening in women aged 39 to 49 years (pooled results from 4 RCTs: relative risk, 0.98 [95% CI, 0.74 to 1.37]) (15).
Screening intervals varied in the trials from 12 to 33 months. Trials using annual screening had no clear differences in outcomes from those using longer intervals (15). Modeling studies designed to compare intervals of screening suggest slightly greater reductions in breast cancer mortality but larger increases in harms—including more false-positive results, benign biopsies, and overdiagnosed cases—with annual versus biennial mammography (5, 18).

Harms

Overdiagnosis and Overtreatment

The association between mammography screening and overdiagnosis has been demonstrated across many studies. However, estimates of the magnitude of overdiagnosis, defined as the detection of cancer through screening that would not otherwise have been diagnosed in a woman's lifetime, varied widely because of lack of a standardized definition and varying methods and metrics used to estimate overdiagnosis (6, 16, 17, 19). Estimates of overdiagnosis from RCTs of screening mammography were higher in women aged 40 to 49 years (range, 22.7% to 41%) than in those aged 50 to 59 years (range, 16% to 25%) (16, 17, 19). After 25 years of follow-up, the estimated overdiagnosis rate was 22% across age groups (19). Estimates from observational studies varied widely because of differences in the populations studied and in methods for estimating overdiagnosis; these estimates ranged from 0% to 54% (6, 17, 19). Modeling studies predict lower rates of overdiagnosis ranging from 2% to 12% over a lifetime horizon, although this number increases with inclusion of ductal carcinoma in situ and other in situ lesions (18).
Overtreatment is defined as treatment of cancer that would not have negatively affected a woman's health in her lifetime. Although reliable estimates of overtreatment are not available, nearly all women diagnosed with breast cancer (including those with ductal carcinoma in situ) receive early treatment with surgery, radiation, hormone therapy, or chemotherapy. Therefore, rates of overtreatment likely resemble estimated rates of overdiagnosis (5).

Other Potential Harms

Appendix Table 2 summarizes false-positive results reported in the evidence reviews. Overall, cumulative rates of receiving at least 1 false-positive result and having a biopsy after 10 years are higher for women of any age having annual versus biennial mammography (16, 17, 19). Pooled rates of receiving at least 1 false-positive result over 10 years of biennial screening ranged from 19.7% to 42% (6, 19). False-negative results are reported at a rate of 10 to 13 in 10 000 women (5).
Several studies have shown that harms from screening results requiring additional follow-up, including false-positive results, lead to the psychological problems of increased breast cancer–specific distress, anxiety, and worry, as well as reduced adherence to subsequent screening (19).
Screening is associated with additional treatments, some of which may not be necessary or effective. Women randomly assigned to screening were more likely to have surgical and radiation therapy; however, use of chemotherapy and hormonal therapy did not differ between groups (6, 16, 19). Treatment harms can be psychological, financial, physical (from surgery, adjunctive radiation, hormonal therapy, and chemotherapy), or related to productivity loss (5). Evidence on quality-adjusted life expectancy was of low quality because of overdiagnosis rates, available utility weights, and uncertainties in estimating life expectancy (19).
Lifetime radiation exposure increases with the number of mammographies, which depends on both the ages of screening initiation and discontinuation and the frequency of screening. Women are exposed to approximately 3.7 mGy per digital mammography (19). Modeling studies report that annual screening of women aged 40 to 74 years was associated with a lifetime attributable risk for radiation-induced breast cancer of 125 cases (CI, 88 to 178 cases) per 100 000 women (20). A modeling study predicted that the number of deaths due to such cancer over a lifetime per 100 000 women ranged from 2 with biennial screening in women aged 50 to 59 years to 11 with annual screening in women aged 40 to 59 years (19).
Pain associated with the screening procedure was commonly reported. Although few patients considered it a deterrent to future screening, failure to attend future screening due to concerns about pain ranged from 11% to 46% (19). None of the evidence reports or guidelines described direct harms of breast biopsies, which include biopsy site pain, bruising, and infection, as well as distress and anxiety.

CBE

Clinical breast examination is a full physical breast examination by a trained clinician; it takes an average of 5 to 10 minutes per breast to do correctly (21, 22). Although CBE continues to be used as part of the examination of symptomatic women, data are sparse on screening asymptomatic women using CBE alone or combined with mammography. Guideline groups vary in their recommendations regarding use of CBE to screen for breast cancer. The ACS recommends against CBE in average-risk women of any age because of the lack of demonstrated benefit and the potential for false-positive results (4). The USPSTF previously stated that evidence was insufficient to assess the benefits and harms of CBE in addition to screening mammography; however, it did not update its 2009 CBE recommendation (5, 11). The CTFPHC provides a conditional recommendation against CBE, citing lack of evidence (7). The WHO suggests that CBE as a standalone screening method could provide a low-cost option in low-resource settings with weak health systems; however, it acknowledges that more evidence is needed (6).

Benefits

No studies show direct clinical benefit of CBE alone or in addition to mammography (17). One RCT and 1 case–control study found no significant reduction in breast cancer mortality or “case fatality” in women having CBE alone or with annual mammography (17). The ACS found that CBE may detect 2% to 6% more cancer cases in addition to mammography (4). Whether increased detection by CBE is beneficial is unknown.

Harms

The biggest harm associated with CBE is false-positive results, and the related harms noted earlier likely also apply here. Rates of false-positive results from limited trials and observational studies were 2.2% to 5% for CBE alone and 3% to 8.7% for CBE combined with mammography, or 55 additional false-positive findings per extra breast cancer case detected with the addition of CBE (17).

Areas of Insufficient Evidence

Other Imaging Methods for First-Line Breast Cancer Screening

None of the guidelines recommend MRI or ultrasonography as the first-line screening method in asymptomatic, average-risk women. The CTFPHC provides a strong recommendation against use of these imaging types because it identified no evidence about their effect on breast cancer outcomes and because screening with these methods would require use of substantial and scarce health care resources without evidence of benefit. No studies have evaluated the effect of MRI, ultrasonography, or DBT on mortality, morbidity, or quality of life. Included studies evaluated diagnostic accuracy characteristics regarding cancer detection, false-positive results, recalls, and biopsy rates. Compared with conventional mammography, DBT seems to reduce recall rates and increase cancer detection (23). The effect of these more sensitive imaging methods on the spectrum of detected disease and associated screening benefits and harms, including overdiagnosis, is not known.

Alternative or Adjunctive Tests to Screening Mammography in Women Who Have Dense Breasts

Increased breast density seems to reduce sensitivity and specificity of mammography for detecting cancer. Women with increased breast density have higher risk for a false-positive result, an unnecessary breast biopsy, or a false-negative result than women with average breast density. Mammography screening RCTs included women with dense breasts but did not provide mortality data according to breast density. The USPSTF, WHO, and CTFPHC recommendations include women with dense breasts in their target population. Breast density classification is further complicated by inconsistency over time and between mammographers (5, 15). The absolute effect of breast density on breast cancer risk is at most small, although most guidelines note that women with dense breasts have higher risk than those without increased breast density (5).
Evidence is insufficient on benefits and harms of primary or adjunctive screening strategies in women who are found to have dense breasts on screening mammography. The USPSTF, WHO, and CTFPHC concluded that evidence is insufficient to assess the balance of benefits and harms of screening for breast cancer in women with dense breasts using other types of imaging (breast ultrasonography, MRI, or DBT) (5–7). In light of the lack of evidence and resource constraints, the CTFPHC recommends against use of these methods to screen for breast cancer in women who are not at increased risk (7). The ACS concluded that mammography alone may be less effective in women with dense breasts but presented no specific data on outcomes (4). The ACS guideline does not provide recommendations on first-line or adjunctive screening in such women.

ACP Guidance Statements

Guidance Statement 1: In average-risk women aged 40 to 49 years, clinicians should discuss whether to screen for breast cancer with mammography before age 50 years. Discussion should include the potential benefits and harms and a woman's preferences. The potential harms outweigh the benefits in most women aged 40 to 49 years.
ACP concludes that the potential harms of screening for breast cancer with mammography before age 50 years outweigh the benefits in most women. The absolute risk reduction in breast cancer mortality is lower in women aged 40 to 49 years than in older women. Overdiagnosis rates vary across age groups (Appendix Table 2) and are higher in women aged 39 to 49 years (6, 17, 19). Cumulative rates of receiving at least 1 false-positive result and having a biopsy after 10 years are higher for younger women, especially in those with heterogeneously or extremely dense breasts.
Women should be informed participants in personalized decisions about breast cancer screening. Those who do not have a clear preference for screening should not be screened. Initiating screening discussions at age 40 years is encouraged for several reasons: Public awareness about breast cancer screening is considerable, and most guidelines recommend at minimum informing women about the potential harms and benefits of screening. Physicians play a key role in helping women accurately sort through the clinical evidence about benefits and harms and in incorporating their personal preferences into individualized screening decisions. It is important for clinicians to convey to women in this age group who may want to be screened that evidence indicates at most small benefits with substantial harms. If a woman still requests screening after a careful discussion of benefits and harms, biennial frequency should be offered.
Current guidelines are more aligned than past versions and have moved toward “less intensive” screening. For example, ACS recommends “offering” mammography as a “qualified recommendation” to women aged 40 through 44 years (4); the USPSTF notes that the net benefit is small in women aged 40 to 49 years and that decisions should be based on an individual woman's values and preferences (5). Guidelines from WHO emphasize screening implementation only in the context of shared decision making and rigorous research for most women regardless of age (6). The CTFPHC conditionally recommends against screening for women aged 40 to 49 years who are not at increased risk and encourages clinicians to focus shared decision-making discussions in this age group on women who express a preference for screening (7). The absolute risk reduction in breast cancer mortality from screening mammography increases with age and takes many years to accrue; the greatest absolute benefit is for women in their 60s. Likewise, all guidelines acknowledge that screening may result in clinically meaningful harms that occur early and may negatively affect a woman's current health status. Thus, they highlight the importance of incorporating individual patients' values and preferences based on the balance of benefits and harms of screening. However, the guidelines disagree on the age at which to start and stop screening and the interval between screening tests. This disagreement primarily stems from how organizations weigh the tradeoffs between the magnitude and importance of reduction in breast cancer mortality and the potential harms from screening mammography (including false-positive results, overdiagnosis, and overtreatment), the reliance and emphasis on observational or modeling data, and the low certainty around the net benefit of screening. No organization specifically incorporates the lack of all-cause mortality benefit, and few assess cost or resource implications of screening. Harms are difficult to fully characterize because most studies, reviews, and guidelines do not assess harms as completely or rigorously as benefits, in part because some harms are more difficult to quantify, measure, and communicate (such as overdiagnosis, overtreatment, psychological harms, quality of life, opportunity costs, and financial costs) than benefits (such as breast cancer–specific mortality). Both CTFPHC and WHO discuss costs in their guideline, and WHO addresses the effect of population-based screening in resource-strained settings (6, 7).
Modeling studies can help illustrate the tradeoff between benefits and harms of screening mammography. Decision models used by the USPSTF show that for every 1000 women screened with mammography (vs. no screening), biennial screening starting at age 40 years will result in 8 fewer breast cancer deaths (but no difference in overall mortality) at the expense of 1529 false-positive results, 213 unnecessary biopsies, and 21 overdiagnosed cancer cases over these women's lifetime (18). In comparison, women starting at age 50 years will have 7 fewer breast cancer deaths at the expense of 953 false-positive results, 146 unnecessary biopsies, and 19 overdiagnosed cancer cases over their lifetime. In light of this tradeoff, uncertainties and assumptions in models, and the variability in how different organizations balance benefits and harms, it is important to engage in shared decision making to understand how an individual woman's risk for breast cancer, screening preferences, and values around benefits and harms affect her net benefit.
Guidance Statement 2: In average-risk women aged 50 to 74 years, clinicians should offer screening for breast cancer with biennial mammography.
Evidence from RCTs shows that screening reduced breast cancer mortality but not all-cause mortality in women aged 50 to 69 years (6, 15–17). Pooled results did not indicate a reduction in all-cause mortality, although individual studies were not designed to detect a difference. Evidence was mixed for breast cancer mortality reduction in women aged 70 to 74 years, although RCT data are limited in this age group. All guidelines agree on screening average-risk women starting at age 50 years and typically continuing through age 74 years. In well-resourced settings with relatively strong health systems, WHO recommends screening women aged 50 to 69 years in the context of shared decision making and screening women aged 70 to 75 years only in the context of shared decision making and rigorous research programs.
Most guidelines recommend biennial mammography as an acceptable or preferred option for women who receive screening (4, 5, 6, 8), and CTFPHC suggests screening every 2 to 3 years (7). No RCTs directly compared different screening intervals. Intervals varied, and outcomes did not differ clearly between trials using annual versus longer screening intervals. Observational studies assessing interval differences did not show a difference in breast cancer mortality between women (aged 50 years or older) who were screened annually versus biennially (15). Reasons for the general trend toward less frequent screening include concerns that more frequent screening will lead to an increase in harms, such as false-positive results, additional breast biopsies, overdiagnosis, overtreatment, and radiation exposure. In women aged 50 to 74 years receiving annual mammography, modeling studies suggested small reductions in breast cancer mortality (2 deaths per 1000 women) and life-years gained (23 life-years per 1000 women) compared with those receiving biennial mammography. However, they had much larger increases in overdiagnosis (6 cases per 1000 women), false-positive results (845 results per 1000 women), unnecessary breast biopsies (82 biopsies per 1000 women), and overtreatment (18).
Guidance Statement 3: In average-risk women aged 75 years or older or in women with a life expectancy of 10 years or less, clinicians should discontinue screening for breast cancer.
Discussions about when to stop screening in women who have received regular mammography screening are particularly important for older persons and for women with limited life expectancy due to comorbid conditions (for example, chronic obstructive pulmonary disease, heart failure, end-stage liver disease, end-stage renal failure, or dementia) (24, 25). The decision to stop screening should incorporate risk for cancer death, competing risk for other causes of death, the long time lag between mammography and reduction in breast cancer mortality, the tradeoffs between benefits and harms, and the individual patient's values and preferences (25). For example, it took an average of almost 11 years before 1 death from breast cancer was prevented for 1000 women screened (26). Although specific recommendations vary, most guidelines suggest discontinuing screening when, on the basis of advanced age or comorbid conditions, a woman is unlikely to have a life expectancy long enough to benefit from screening (4–9)—typically 10 years.
Although accurately calculating an individual's life expectancy is difficult, decisions informed in part by average life expectancy for a specific age may be helpful (25, 27). Among women aged 70 and 75 years with no comorbid conditions, life expectancy is 19 and 15 years, respectively (28). However, among 70- and 75-year-old women with serious comorbid conditions, average life expectancy is approximately 11 and 9 years, respectively (28).
Guidance Statement 4: In average-risk women of all ages, clinicians should not use clinical breast examination to screen for breast cancer.
Evidence is lacking for a mortality benefit of CBE alone or in combination with mammography in asymptomatic women at average risk; CBE can also result in harms, including overdiagnosis and false-positive results leading to overtreatment. Clinical breast examination takes about 5 to 10 minutes to do—time that could be devoted to health care interventions of greater proven net benefit. As such, no guideline recommends screening with CBE if mammography is available.
The Figure summarizes the guidance, clinical considerations, and talking points for patients.
Figure. Summary of the American College of Physicians guidance statement on breast cancer screening in average-risk women. CBE = clinical breast examination; USPSTF = U.S. Preventive Services Task Force.
Figure. Summary of the American College of Physicians guidance statement on breast cancer screening in average-risk women.
CBE = clinical breast examination; USPSTF = U.S. Preventive Services Task Force.

Appendix: Summary of Evaluated Guidelines to Inform the ACP Guidance Statement

American College of Obstetricians and Gynecologists Recommendations

Recommendations Based on Good and Consistent Scientific Evidence (Level A)

“Women at average risk of breast cancer should be offered screening mammography starting at age 40 years. Women at average risk of breast cancer should initiate screening mammography no earlier than age 40 years. If they have not initiated screening in their 40s, they should begin screening mammography by no later than age 50 years. The decision about the age to begin mammography screening should be made through a shared decision-making process. This discussion should include information about the potential benefits and harms.
“Women at average risk of breast cancer should have screening mammography every 1 or 2 years based on an informed, shared decision-making process that includes a discussion of the benefits and harms of annual and biennial screening and incorporates patient values and preferences. Biennial screening mammography, particularly after age 55 years, is a reasonable option to reduce the frequency of harms, as long as patient counseling includes a discussion that with decreased screening comes some reduction in benefits.
“Women at average risk of breast cancer should continue screening mammography until at least age 75 years” (8).

Recommendations Based on Limited or Inconsistent Scientific Evidence (Level B)

“Health care providers periodically should assess breast cancer risk by reviewing the patient's history.
“Women with a potentially increased risk of breast cancer based on initial history should have further risk assessment.
“Breast self-examination is not recommended in average-risk women because there is a risk of harm from false-positive test results and a lack of evidence of benefit” (8).

Recommendations Based Primarily on Consensus and Expert Opinion (Level C)

“Screening clinical breast examination may be offered to asymptomatic, average-risk women in the context of an informed, shared decision-making approach that recognizes the uncertainty of additional benefits and the possibility of adverse consequences of clinical breast examination beyond screening mammography. If performed for screening, intervals of every 1–3 years for women aged 25–39 years and annually for women aged 40 years and older are reasonable. The clinical breast examination continues to be a recommended part of evaluation of high-risk women and women with symptoms.
“Average-risk women should be counseled about breast self-awareness and encouraged to notify their health care provider if they experience a change. Breast self-awareness is defined as a woman's awareness of the normal appearance and feel of her breasts.
“Age alone should not be the basis to continue or discontinue screening. Beyond age 75 years, the decision to discontinue screening mammography should be based on a shared decision making process informed by the woman's health status and longevity” (8).

American College of Radiology Recommendations

“For average-risk women, annual screening mammography or DBT (with accompanying planar or synthesized [2-dimensional] images) is recommended beginning at age 40. For women with dense breasts, [ultrasonography] may also be considered, but the balance between increased cancer detection and the increased risk of a false-positive examination should be considered in the decision” (9).

ACS Recommendations

“The ACS recommends that women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation). Women aged 45 to 54 years should be screened annually (qualified recommendation). Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (qualified recommendation). Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation). Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (qualified recommendation). The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation)” (4).

CTFPHC Recommendations

Mammography

“Screening women aged 40 to 49 years: For women aged 40 to 49 years, we recommend not screening with mammography; the decision to undergo screening is conditional on the relative value a woman places on possible benefits and harms from screening (conditional recommendation; low-certainty evidence).
“Screening women aged 50 to 69 years: For women aged 50 to 69 years, we recommend screening with mammography every 2 to 3 years; the decision to undergo screening is conditional on the relative value that a woman places on possible benefits and harms from screening (conditional recommendation; very low-certainty evidence).
“Screening women aged 70 to 74 years: For women aged 70 to 74 years, we recommend screening with mammography every 2 to 3 years; the decision to undergo screening is conditional on the relative value that a woman places on possible benefits and harms from screening (conditional recommendation; very low certainty evidence)” (7).

Other Screening Methods

“We recommend not using magnetic resonance imaging, tomosynthesis or ultrasound to screen for breast cancer in women who are not at increased risk (strong recommendation; no evidence).
“We recommend not performing clinical breast examinations to screen for breast cancer (conditional recommendation; no evidence).
“We recommend not advising women to practise breast self-examination to screen for breast cancer (conditional recommendation; low-certainty evidence) “ (7).

NCCN Recommendations

Average-Risk Women Aged 25 to 39 Years

“The NCCN panel recommends a clinical encounter, which includes ongoing breast cancer risk assessment, risk reduction counseling, as well as a CBE every 1 to 3 years and encouraging women to be aware of their breasts and promptly report any changes to their health care provider” (10).

Average-Risk Women Aged 40 Years or Older

“The NCCN panel recommends annual clinical encounter, which includes ongoing breast cancer risk assessment, risk reduction counseling, as well as a CBE, and encourages women to be aware of their breasts and promptly report any changes and annual screening mammography (category 1 recommendation) with the consideration of tomosynthesis. Women electing to undergo screening mammography should be counseled regarding its potential benefits, risks, and limitations” (10).

USPSTF Recommendations

“The USPSTF recommends biennial screening mammography for women aged 50 to 74 years. (B recommendation).
“The decision to start screening mammography in women prior to age 50 years should be an individual one. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. (C recommendation)
“The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older. (I statement)
“The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of DBT as a primary screening method for breast cancer. (I statement)
“The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, MRI, DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement)” (5).

WHO Recommendations

Women Aged 50 to 69 Years in Well-Resourced Settings

“In well-resourced settings, WHO recommends organized, population-based mammography screening programmes for women aged 50–69 years if the conditions for implementing an organized programme specified in this guide are met by the health-care system, and if shared decision-making strategies are implemented so that women's decisions are consistent with their values and preferences. (Strong recommendation based on moderate quality evidence)
“WHO suggests a screening interval of two years. (Conditional recommendation based on low quality evidence)” (6).

Women Aged 50 to 69 Years in Low-Resource Settings With Relatively Strong Health Systems

“In limited resource settings with relatively strong health systems, WHO suggests considering an organized, population-based mammography screening programme for women aged 50–69 years only if the conditions for implementing an organized programme specified in this guide are met by the health-care system, and if shared decision-making strategies are implemented so that women's decisions are consistent with their values and preferences. (Conditional recommendation based on moderate quality evidence)
“WHO suggests a screening interval of two years. (Conditional recommendation based on low quality evidence)” (6).

Women Aged 50 to 69 Years in Low-Resource Settings With Weak Health Systems

“In limited resource settings with weak health systems, where the majority of women with breast cancer are diagnosed in late stages and mammography screening is not cost-effective and feasible, early diagnosis of breast cancer through universal access of women with symptomatic lesions to prompt and effective diagnosis and treatment should be high on the public health agenda. Clinical breast examination, a low-cost screening method, seems to be a promising approach for these settings and could be implemented when the necessary evidence from ongoing studies becomes available” (6).

Women Aged 40 to 49 Years in Well-Resourced Settings

“In well-resourced settings, WHO suggests an organized, population-based screening programme for women aged 40–49 years only if such programme is conducted in the context of rigorous research and monitoring and evaluation, if the conditions for implementing an organized programme specified in this guide are met and if shared decision-making strategies are implemented so that women's decisions are consistent with their values and preferences. (Conditional recommendation based on moderate quality evidence)” (6).

Women Aged 40 to 49 Years in Low-Resource Settings With Weak or Relatively Strong Health Systems

“In limited resource settings with weak or relatively strong health systems, WHO recommends against the implementation of population-based screening programmes for women aged 40–49 years. (Strong recommendation based on moderate quality evidence)” (6).

Women Aged 70 to 75 Years in Well-Resourced Settings

“In well-resourced settings, WHO suggests an organized, population-based screening programme for women aged 70–75 years only if such programme is conducted in the context of rigorous research, if the conditions for implementing an organized programme specified in this guide are met by the health-care system, and shared decision-making strategies are implemented so that women's decisions are consistent with their values and preferences. (Conditional recommendation based on low quality evidence)” (6).

Women Aged 70 to 75 Years in Low-Resource Settings With Weak or Relatively Strong Health Systems

“In limited resource settings with weak or relatively strong health systems, WHO recommends against the implementation of population-based screening programmes for women aged 70–75 years. (Strong recommendation based on low quality evidence)” (6).

References

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National Cancer Institute. Cancer Stat Facts: Female Breast Cancer. Bethesda, MD: National Cancer Institute. Accessed at https://seer.cancer.gov/statfacts/html/breast.html on 30 October 2018.
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Harris RPWilt TJQaseem AHigh Value Care Task Force of the American College of Physicians. A value framework for cancer screening: advice for high-value care from the American College of Physicians. Ann Intern Med. 2015;162:712-7. [PMID: 25984846].  doi: 10.7326/M14-2327
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Wilt TJHarris RPQaseem AHigh Value Care Task Force of the American College of Physicians. Screening for cancer: advice for high-value care from the American College of Physicians. Ann Intern Med. 2015;162:718-25. [PMID: 25984847].  doi: 10.7326/M14-2326
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Oeffinger KCFontham ETEtzioni RHerzig AMichaelson JSShih YCet alAmerican Cancer Society. Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA. 2015;314:1599-614. [PMID: 26501536]  doi: 10.1001/jama.2015.12783
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Siu ALU.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164:279-96. [PMID: 26757170].  doi: 10.7326/M15-2886
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World Health Organization. WHO Position Paper on Mammography Screening. Geneva: WHO Pr; 2014. Accessed at www.who.int/cancer/publications/mammography_screening/en on 18 January 2018.
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Klarenbach SSims-Jones NLewin GSingh HThériault GTonelli Met al. Recommendations on screening for breast cancer in women aged 40–74 years who are not at increased risk for breast cancer. Can Med Assoc J. 2018;190:E1441-51.  doi: 10.1503/cmaj.180463
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Practice bulletin no. 179 summary: breast cancer risk assessment and screening in average-risk women. Obstet Gynecol. 2017;130:241-3. [PMID: 28644328]  doi: 10.1097/AOG.0000000000002151
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Mainiero MBMoy LBaron PDidwania ADdiFlorio RMGreen EDet alExpert Panel on Breast Imaging:. ACR appropriateness criteria breast cancer screening. J Am Coll Radiol. 2017;14:S383-90. [PMID: 29101979]  doi: 10.1016/j.jacr.2017.08.044
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National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2.2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf on 7 June 2018.
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US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:716-26, W-236. [PMID: 19920272].  doi: 10.7326/0003-4819-151-10-200911170-00008
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Schünemann H, Brożek J, Guyatt G, Oxman A, eds. GRADE Handbook. 2013. Accessed at http://gdt.guidelinedevelopment.org/app/handbook/handbook.html on 11 April 2018.
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Brouwers MCKho MEBrowman GPBurgers JSCluzeau FFeder Get al. AGREE II: advancing guideline development, reporting and evaluation in health care. Can Med Assoc J. 2010;182:E839-42.  doi: 10.1503/cmaj.090449
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AGREE II. Accessed at www.agreetrust.org/agree-ii on 9 October 2018.
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Nelson HDFu RCantor APappas MDaeges MHumphrey L. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2016;164:244-55. [PMID: 26756588].  doi: 10.7326/M15-0969
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Barbeau P, Stevens A, Beck A, Skidmore B, Arnaout A, Brackstone M, et al. Breast Cancer Screening: Part A. An Evidence Report to Inform an Update of the Canadian Task Force on Preventive Health Care 2011 Guideline. 2017. Accessed at https://canadiantaskforce.ca/wp-content/uploads/2018/11/Evidence-Report-Breast-Cancer-Screening_FINAL.pdf on 10 January 2019.
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Myers ERMoorman PGierisch JMHavrilesky LJGrimm LJGhate Set al. Benefits and harms of breast cancer screening: a systematic review. JAMA. 2015;314:1615-34. [PMID: 26501537]  doi: 10.1001/jama.2015.13183
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Mandelblatt JSStout NKSchechter CBvan den Broek JJMiglioretti DLKrapcho Met al. Collaborative modeling of the benefits and harms associated with different U.S. breast cancer screening strategies. Ann Intern Med. 2016;164:215-25. [PMID: 26756606].  doi: 10.7326/M15-1536
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Nelson HDPappas MCantor AGriffin JDaeges MHumphrey L. Harms of breast cancer screening: systematic review to update the 2009 U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2016;164:256-67. [PMID: 26756737].  doi: 10.7326/M15-0970.
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Miglioretti DLLange Jvan den Broek JJLee CIvan Ravesteyn NTRitley Det al. Radiation-induced breast cancer incidence and mortality from digital mammography screening: a modeling study. Ann Intern Med. 2016;164:205-14. [PMID: 26756460].  doi: 10.7326/M15-1241
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Fuller MSLee CIElmore JG. Breast cancer screening: an evidence-based update. Med Clin North Am. 2015;99:451-68. [PMID: 25841594]  doi: 10.1016/j.mcna.2015.01.002
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Provencher LHogue JCDesbiens CPoirier BPoirier EBoudreau Det al. Is clinical breast examination important for breast cancer detection? Curr Oncol. 2016;23:e332-9. [PMID: 27536182]  doi: 10.3747/co.23.2881
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Melnikow JFenton JJWhitlock EPMiglioretti DLWeyrich MSThompson JHet al. Supplemental screening for breast cancer in women with dense breasts: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:268-78. [PMID: 26757021].  doi: 10.7326/M15-1789
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Eckstrom EFeeny DHWalter LCPerdue LAWhitlock EP. Individualizing cancer screening in older adults: a narrative review and framework for future research. J Gen Intern Med. 2013;28:292-8. [PMID: 23054920]  doi: 10.1007/s11606-012-2227-x
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Walter LCCovinsky KE. Cancer screening in elderly patients: a framework for individualized decision making. JAMA. 2001;285:2750-6. [PMID: 11386931]
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Lee SJBoscardin WJStijacic-Cenzer IConell-Price JO'Brien SWalter LC. Time lag to benefit after screening for breast and colorectal cancer: meta-analysis of survival data from the United States, Sweden, United Kingdom, and Denmark. BMJ. 2013;346:e8441. [PMID: 23299842]  doi: 10.1136/bmj.e8441
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Rector T, Taylor B, Sultan S, Shaukat A, Adabag S, Nelson D, et al. Life Expectancy Calculators. Washington, DC: U.S. Department of Veterans Affairs; June 2016. Accessed at www.ncbi.nlm.nih.gov/books/NBK424560 on 26 February 2019.
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Cho HKlabunde CNYabroff KRWang ZMeekins ALansdorp-Vogelaar Iet al. Comorbidity-adjusted life expectancy: a new tool to inform recommendations for optimal screening strategies. Ann Intern Med. 2013;159:667-76. [PMID: 24247672].  doi: 10.7326/0003-4819-159-10-201311190-00005

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Richard Fleming, PhD, MD, JD21 October 2019
Does someone have cancer? – This really isn’t a yes-no question.
For decades we have been running screening tests looking for cancer, allowing physicians to make an educated guess as to whether we think you do or don’t have cancer. If we think the patient might have cancer, then we run more tests to find out. Alternatively, if we think the patient probably doesn’t have cancer, we wait –so too does the patient and their family. The entire concept of using screening tests is archaic and anything but comfortable if you’re the patient.

The acceptance of screening tests is primarily based on the use of qualitative tests – tests that we look at, or blood tests. Is there something on the stool guaiac? Is it blood, iron, too much pepto bismol? Is the PSA elevated? Is it prostate cancer, prostatitis, BPH, too much exercise? In keeping with October - Breast Cancer Awareness month – the question becomes, just what is that questionable area on the mammogram – is it calcium, dense tissue, inflammation, cancer or nothing?

The process of developing cancer is not an overnight, yes - no phenomena; although that is how we’ve been treating it [1]. Cancer is the result of the interaction between the genetics of a cell – which is unique for each individual – and the cellular environment. That cellular environment is similarly unique and is the result of the air you breathe, the food you eat, the oxidative stress your body is experiencing at the moment, is there infection, et cetera [2].

Rather than using a qualitative screening approach, with the associated problems with sensitivity (we missed your disease) and specificity (we told you there was a problem when there wasn’t), and the resulting personal, psychological, physical, financial, family, work costs – if we’re really interested in informed decision making, we should be focusing less on screening and more on actually measuring what’s happening in the body.

It turns out that the changes which happen in the body leading to the development of both cancer and coronary artery disease, can now be measured by looking at changes in metabolism and regional blood flow [3].

By being able to measure what’s actually happening, we can tell someone where on the health-spectrum he or she actually is [1,2]. We can measure whether their treatment is working – saving time, money and lives – thus providing true patient-specific, patient-guided treatment. By actually measuring what’s happening in each individual, we can do better than guess – we can make a truly informed decision and so can the patient.

Acknowledgment: FMTVDM is issued to first author.

References:

1. Fleming RM, Fleming MR, Chaudhuri TK, McKusick A. Cancer: Our Body’s Global Warming Warning. Biomed Research. Open Acc J Oncol Med 2019;3(1):238-239. DOI: 10.32474/OAJOM.2019.03.000154
2. Fleming RM, Fleming MR. The Importance of Thinking about and Quantifying Disease like Cancer and Heart Disease on a “Health-Spectrum” Continuum. J Compr Cancer Rep 2019;3(1):1-3 (Article ID 100011).
3. Fleming RM, Fleming MR, Chaudhuri TK. The Similarities in Coronary Artery Disease and Cancer. Acta Scientific Med Sci. 2019;Special Issue 1:03-04. DOI:10.31080/ASMS.2019.S01.0002.

Disclosures: FMTVDM issued to author.

Jennifer S. Lin, MD, MCR, Reem A. Mustafa, MD, MPH, Timothy J. Wilt, MD, MPH, Carrie A. Horwitch, MD, MPH, Amir Qaseem, MD, PhD, MHA18 July 2019
Author's Response
We appreciate comments from Drs. Biggs, Grimm, Lenderink-Carpenter, and Lee and colleagues and the opportunity our guidance statements provide to engage in robust peer discussions. We emphasize the broad agreement across our guidance statements among guideline groups including for women ages 40-49 (1). None of the guidelines recommend screening in women aged 40 to 45; the ACS suggested starting age of 45 years is a weak recommendation due to the fine balance between benefits and harms and the importance of individual patient values and preferences. In women younger than 50 years, we reassert that the evidence - including data from two guidelines based on more recent trials with longer follow-up (including AGE and CNBSS-1) - demonstrates that the absolute risk of breast cancer screening harms is high and that the absolute benefit in breast cancer mortality reduction is very low (1,2). The ACS and WHO guidelines are not two independent sources as they were based on the same data set that did not include updated results from the AGE or CNBSS-1 trials (3, 4). We considered many harms including overdiagnosis, overtreatment, false-positives, radiation exposure, and others (of which psychological stressors are only one aspect). Thus, we disagree with Drs. Biggs, Grimm, and Lenderink-Carpenter’s assessments of net benefit. We and others (2,5) disagree with Dr. Lenderink-Carpenter that modeling represents the most accurate assessment of overdiagnosis – modeling incorporates many assumptions, some unknowable. Our understanding should be informed by all available data, which we discussed at length and summarized in Appendix Table 2 (1).

We appreciate Dr. Lenderink-Carpenter’s agreement with us regarding the physician’s role in helping patients sort through the evidence and Dr. Grimm’s point that discussions should be personalized. For women age 40-49, our guidance statement encourages physicians to discuss whether to screen for breast cancer. Hence, our guidance statements include data derived talking points about the benefits and harms of screening to assist in physician-patient communication and facilitate personalized breast cancer screening decisions. This includes information so that women younger than 50, older than 75, or with a life expectancy less than 10 years understand the small average benefit relative to substantial harm. This discussion should include considerations raised by Dr. Lee and colleagues related to racial disparities. Although no guideline defined risk status by race or ethnicity, we agree that research is needed to understand the drivers underlying disproportionate breast cancer morbidity and mortality in black women.

Jennifer S. Lin, MD, MCR, Kaiser Permanente Northwest, Portland, Oregon
Reem A. Mustafa, MD, MPH, University of Kansas Medical Center, Kansas City, KS
Timothy J. Wilt, MD, MPH, Minneapolis VA Center for Chronic Disease Outcomes Research and University of Minnesota School of Medicine, Minneapolis, Minnesota
Carrie A. Horwitch, MD, MPH, Virginia Mason Medical Center, Seattle, WA
Amir Qaseem, MD, PhD, MHA, American College of Physicians, Philadelphia, PA


References


1. Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ, Physicians ftCGCotACo. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of PhysiciansACP Guidance Statement on Breast Cancer Screening in Average-Risk Women. Annals of Internal Medicine. 2019;170(8):547-60.
2. Redberg RF, Grady D. False Information About Breast Cancer Screening-Reply. JAMA Intern Med. 2018;178(2):300.
3. Moss SM, Wale C, Smith R, Evans A, Cuckle H, Duffy SW. Effect of mammographic screening from age 40 years on breast cancer mortality in the UK Age trial at 17 years' follow-up: a randomised controlled trial. Lancet Oncol. 2015;16(9):1123-32.
4. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ : British Medical Journal. 2014;348.
5. Nelson HD, Fu R, Cantor A, Pappas M, Daeges M, Humphrey L. Effectiveness of breast cancer screening: Systematic review and meta-analysis to update the 2009 u.s. preventive services task force recommendation. Annals of Internal Medicine. 2016;164(4):244-55.
William T. Phillips, Ralph Blumhardt29 April 2019
Screening for breast cancer, are guidelines misguided?
The first guidance statement from the American College of Physicians (1) leaves it to the clinician and patient to decide if screening mammography is beneficial for patients from 40 to 49 years of age. In comparing benefits vs. harm, the clinician should point out that patients undergoing mammography may have a risk of 11 radiation-induced breast cancer deaths out of 100,000 women. This based on a "modeling study" (2) that assumes that all radiation exposure is additive and equivalent to one time exposure of Hiroshima victims. On the beneficial side, a study has shown a reduction of 968 breast cancer deaths per 100,000 women age 40 to 74 years (3). To us, the choice is obvious. Ask any oncologist, how often they had patients with terminal breast cancer regret the they did not undergo screening mammography.

References: 


1. Qaseem A, Lin,JS, Mustafa RA, Horwitch CA, Wilt TJ. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians
Ann Intern Med. 2019;170:547-60. doi:10.7326/M18-2147


2. Nelson HD, Pappas M, Cantor A, Griffin J, Daeges M, Humphrey L. Harms of breast cancer screening: systematic review to update the 2009 U.S. Preventive Services Task Force recommendation. Ann Int Med. 2016;164:256-67. doi:10.7326/M15-0970.


3. Nelson HD, Fu R, Cantor A. Pappas M, Daeges M, Humphrey L. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 U.S. Preventive Service Task Force recommendation. Ann Int Med. 2016;164:244-55. doi:10.7326/M15-0969
Lora D. Barke DO, Luke Hoagland MD22 April 2019
Guidance is Misleading
The article “Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians” contains multiple misleading and objectively false statements. Beginning with the first line “breast cancer is the… fourth leading cause of cancer death”. This would be immediately recognized as false by an expert in the field. The provided reference actually demonstrates breast cancer is the third leading cause for all cancer deaths, but even then, only when combining data for men with colorectal cancer. The germane fact is, breast cancer is by far the single leading cause of cancer death among all women who don’t smoke.
The article additionally claims “low incidence of breast cancer for women younger than 60 years”. Interestingly, but unsurprisingly, a reference does not accompany this inflammatory and false statement. In fact, 44% of all breast cancers occur within this cohort [1]. Dismissing this as “low incidence” demonstrates unfamiliarity and/or bias regarding the facts.
The article subjectively places heavy emphasis on screening harms, particularly “overdiagnosis” (more accurately “overtreatment”). Ironic given the recommended biennial screening would be sure to catch all slower growing cancers while allowing more aggressive cancers time to become uncurable. Further, Guidance Statement 1 states, “potential harms outweigh the benefits in most women aged 40 to 49 years.” While “overdiagnosis” has been shown to be minimal among all age groups when actual patient data is analyzed, it is virtually non-existent for women in their 40s [2]. These younger women are more likely to be healthy, active, working, and raising children. They also tend to develop more aggressive breast cancers. It is a fact, more life-years are lost to women diagnosed with breast cancer in their 40s than any decade before or after [3].
Integral to shared decision making is understanding the underlying science by both the patient and provider. Primary providers stereotypically have exceptionally full plates. However, a feeling of sympathy for their task inherently comes with recognition of bias. Complying with guidelines becomes easier when science is ignored and guidelines relaxed. The accompanying editorial sounds a familiar chime of suggesting guidelines from experts can be dismissed due to bias [4]. However, the cited reference simply demonstrates a correlation of expertise with recommendation for screening [5]. All stakeholders bring some bias to the table. However, dismissing the inconvenient science and opinions of experts by claiming “bias” carries no greater weight than dismissing inconvenient journalism as “fake news”.

1. American Cancer Society. Breast Cancer Facts and Figures 2017-2018. Atlanta, GA: Accessed at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2017-2018.pdf on 16 April 2019.
2. Hendrick RE. Obligate Overdiagnosis Due to Mammographic Screening: A Direct Estimate for U.S. Women. Radiology. 2017; 287(2):391-397
3. Oeffinger KC, Fontham ETH, Etziono R, Herzig A, Michaelson JS, Shih YT, et al. Breast Cancer Screening for Women at Average Risk 2015 Guideline Update From the American Cancer Society. JAMA. 2015; 314:1599-1614.
4. Elmore JG, Lee CI. A Guide to a Guidance Statement on Screening Guidelines. Ann Intern Med. 2019; 1-2.
5. Norris SL, Burda BU, Holmer HK, Ogden LA, Fu R, Bero L, et al. Author's specialty and conflicts of interest contribute to conflicting guidelines for screening mammography. J Clin Epidemiol. 2012;65:725-33.
Margaret Fleming, MD, MSc19 April 2019
ACP guidelines make decisions FOR women that instead should be made BY women
To the Editor:

It was with concern that I read the American College of Physicians (ACP) guidance statement on breast cancer screening. The statement fails to assert many of the benefits of screening mammography, particularly yearly mammography starting at age 40. As a result, decisions about breast cancer screening are being made for women instead of by women for themselves.

The article asserts that “the potential harms outweigh the benefits in most women aged 40-49 years.” However, the authors fail to mention that annual mammographic screening from ages 40 to 84 saves 5 more lives per 1000 women than biennial screening of women aged 50-74 years (1). Furthermore, the authors discuss mortality reduction with annual screening starting at age 40, but fail to mention that annual screening starting at age 40 results in the most life years gained (2).

Excluding women in their 40s from breast cancer screening also disproportionately affects women of color who are diagnosed at earlier ages than white women. Black, Hispanic, and Asian women have a peak incidence of breast cancer at less than 50 years old (3). Therefore, ACP guidelines more negatively affect black, Hispanic, and Asian women than white women, further exacerbating disparities experienced by women of color.

To be clear, annual screening starting at age 40 may not be the best choice for every woman. However, we should let that be a choice FOR HER and BY HER, not the choice of people who do not know her preferences. With numerous differing guidelines by many groups, the average woman may have difficulty navigating the various recommendations. This can be simplified: Annual screening starting at age 40 saves the most lives. If we as providers can be unified in delivering that message, then from there, each woman can make the choice of what is right for her.

References

1. Hendrick RE, Helvie MA. United States Preventive Services Task Force Screening Mammography Recommendations: science ignored. AJR 2011; 196:338.
2. Mandelblatt JS, Cronin KA, Bailey S, et al. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med2009;151(10):738–747.
3. Stapleton SM, Oseni TO, Bababekov YJ, Hung YC, Chang DC. Race/Ethnicity and Age Distribution of Breast Cancer Diagnosis in the United States. JAMA Surg. Jun 1 2018;153(6):594-595.

Margaret M. Fleming, MD, MSc
Assistant Professor of Radiology and Imaging Sciences
Emory University School of Medicine
Atlanta, Georgia
[email protected]

Conflicts of interest: None
Dipti Gupta15 April 2019
ACP guidelines: NOT saving lives
The American College of Physicians motto is “leading internal medicine, saving lives.” The recent breast cancer screening guidance statement released by the ACP contradict its very motto – by not saving lives. In fact, the recommendation to screen only women age 50-74 every other year may lead to 10,000 unnecessary breast cancer related deaths in the US each year[1]. This does not even include thousands more women who would have to undergo more aggressive treatment for advanced breast cancer, including mastectomy and chemotherapy.
The current guidance statement is associated with only a 23% reduction in breast-cancer related deaths, as opposed to nearly 40% reduction with annual screening mammography starting at age 40[2]. All major societies including the US Preventive Services Task Force and the American Cancer Society agree that the most lives are saved when women are screened annually starting at age 40.
The ACP guidance statement greatly overstates the supposed harms of screening mammography and underestimates its life saving benefits[3]. If ACP wants to stay true to its value of saving lives, the guidance statement must be revised to annual screening mammography starting at age 40.

1. Hendrick, R.E. and M.A. Helvie, United States Preventive Services Task Force screening mammography recommendations: science ignored. AJR Am J Roentgenol, 2011. 196(2): p. W112-6.
2. Arleo, E.K., et al., Comparison of recommendations for screening mammography using CISNET models. Cancer, 2017. 123(19): p. 3673-3680.
3. Monticciolo, D.L., M.A. Helvie, and R.E. Hendrick, Current Issues in the Overdiagnosis and Overtreatment of Breast Cancer. AJR Am J Roentgenol, 2018. 210(2): p. 285-291.
Jiyon Lee MD, Paula B. Gordon MD, Vilert Loving MD15 April 2019
“Anxiety” not a “harm”: time to normalize, recalibrate, and mitigate as normal and manageable. We’re all in this together.
“Anxiety” and “false positives” as “harms” seem to be considered greater than the potential harms of underdiagnosis and missed opportunities to make early detections and save the 100,000 lives that could be lost to breast cancer using ACP/USPSTF guidelines.[1,2] Historically around breast screening, those terms’ usage seems to be helpless perseveration without definition or correction.

It’s time to call the medical testing anxiety what it is and all help ameliorate it as we go. Recalibration of the term anxiety as a usually normal range of experience and engaging in ways to mitigate [3] and help manage would change the assessment of “risk” of screening. For most people, the anxiety is situational, transient, and resolvable [4], albeit potentially amplified in breast screening for reasons such as the number of people affected and the decades of serial screening involved. Yes, it does take stamina. And conviction that it’s worthwhile. It also takes access and proper support for follow through. And you know what? We are ALL in this together.

Radiologists are strong supporters of screening not only because we know the data, but because we take care of women. We know that the data show that annual mammography starting at the age of 40 saves the most lives. We see all the effects of screening – the true positives, true negatives, false positives, and false negatives and we understand the consequences for our patients. We do it all, from screening to detection to biopsy confirmation of benign, atypical, and malignant, and we see the range of patient outcomes. We are not an inexpert panel who tries to assess data without understanding its validity and importance. We know that mammography is imperfect, but we have watched as we have been finding small cancers and the death rate has gone down. Our conviction about screening is based on knowledge and clinical experiential wisdom. That conviction carries through our recommendations for our loved ones and ourselves [5] as we attend screening at high rates, all being human and aging like everyone else.

Fortunately, many PCPs [6] support annual screening starting at age 40y. My colleagues and I are compassionate and empathic and understand the anxiety of screening, but we are able to tell most women that everything is fine. And for those 1/8 women in the US who will develop cancer, we know early detection affords better chances. As a woman I resent the fact that an inexpert panel is telling me that women in their forties cannot deal with the transient anxiety and we should allow thousands to die, unnecessarily to avoid recalls. As breast imagers, our anxiety is about the missed opportunities to make a difference.

References:
1.Arleo EK, Hendrick RE, Helvie MA, Sickles EA. Comparison of recommendations for screening mammography using CISNET models. Cancer. 2017 Oct 1;123(19):3673-3680.
2.Hendrick RE, Helvie MA. USPSTF Guidelines on Screening Mammography Recommendations: Science Ignored. Am. J. Roentgenology 2011; 196: W112 - W116.
3.Lee J, Hardesty LA, Kunzler NM, Rosenkrantz AB. Direct Interactive Public Education by Breast Radiologists About Screening Mammography: Impact on Anxiety and Empowerment.
J Am Coll Radiol. 2016 Jan;13(1):12-20. doi: 10.1016/j.jacr.2015.07.018. Epub 2015 Oct 17.
4.Tosteson A, et al. Consequences of False-positive Screening Mammograms. JAMA. 2014;174(6):954-961.
5.Lee J, Gordon PB, Whitman GJ. "Do unto others as you would have them do unto you": breast imagers' perspectives regarding screening mammography for others and for themselves--do they practice what they preach? AJR Am J Roentgenol. 2015 Jun;204(6):1336-44. doi: 10.2214/AJR.14.13237
6.Radhakrishnan A, Nowak SA, Parker AM, Visvanathan K, Pollack CE.
Physician Breast Cancer Screening Recommendations Following Guideline Changes: Results of a National Survey. JAMA Intern Med. 2017 Jun 1;177(6):877-878. doi: 10.1001/jamainternmed.2017.0453.

Jiyon Lee, MD
Clinical Associate Professor of Radiology
NYU School of Medicine

Paula B. Gordon, MD
Clinical Professor
University of British Columbia

Vilert Loving, MD MMM
Chief of Breast Imaging
Banner MD Anderson Cancer Center
Gilbert, Arizona
David V. Schacht, Sarah M. Friedewald15 April 2019
Saving lives and gaining life years through modern mammography screening of women in their 40s
To The Editor:
Providing patients with recommendations that are grounded in scientific evidence is at the heart of the practice of modern medicine. When presenting factual data, we empower our patients and avoid the paternalism of the past. It is therefore concerning to see that the guidelines issued by the ACP may not live up to these expectations.
All organizations agree that screening mammography beginning at age 40 provides the greatest reduction in mortality. Specific to women ages 40-49, significant mortality benefit has also been demonstrated. (1) Beyond the mortality benefits for women in their forties, the life years gained for diagnosing a woman in this age group is greater than for an older woman. From a societal perspective, preserving the lives of younger women is critical as they are often in the primes of their careers and responsible for caring for two generations- both young children and aging parents.
We know that most women are willing to accept the need for additional tests that necessarily occur in order to diagnose breast cancers before they become clinically evident (2). The paternalistic approach of deciding that the short term discomfort and anxieties associated with this process are more harmful than saving lives is a step back in our efforts to empower women to choose for themselves. Any recommendation that advocates initiation of screening later than 40 or at fewer than yearly intervals for the average patient will result in increased morbidity and mortality and is contrary to what most women would choose.
Additionally, new technology, specifically, digital breast tomosynthesis (DBT) improves upon the limitations of traditional mammography. Women in their 40s who are screened with DBT have similar false positive rates and cancer detection rates as women in their 50s who are screened with traditional mammography. (3) Although there are as of yet no long term outcome data that demonstrate decreased mortality when screening patients with DBT, the reduction in false positive examinations alone should be emphasized. Once patients have been routinely screened with DBT, the false positive examinations are decreased by nearly half. (4) These data were excluded from the ACP recommendations, despite DBT’s widespread use in the United States.
We are obligated to provide the most up to date and accurate information for our patients, to allow patients to choose whether or not they follow the guidelines and not deny patients who could benefit from lifesaving technology.

References:
1. Hellquist BN, Duffy SW, Abdsaleh S, et al. Effectiveness of population-based service screening with mammography for women ages 40 to 49 years: evaluation of the Swedish Mammography Screening in Young Women (SCRY) cohort. Cancer 2011; 117:714-722.
2. Ganott MA, Sumkin JH, King JL et al. Screening mammography: Do women prefer a higher recall rate given the possibility of earlier detection of cancer? Radiology 2006; 238(3):793-800.
3. Conant EF, Barlow WE, Herschorn SD et al. Association of Digital Breast Tomosynthesis vs Digital Mammography With Cancer Detection and Recall Rates by Age and Breast Density. JAMA Oncol. 2019 Feb 28 [Epub ahead of print]
4. McDonald ES, Oustimov A, Weinstein SP et al. Effectiveness of Digital Breast Tomosynthesis Compared With Digital Mammography: Outcomes Analysis From 3 Years of Breast Cancer Screening. JAMA Oncol. 2016 Jun 1;2(6):737-43
Aya Michaels, MD12 April 2019
The risks of mammography were overstated.
The “harms” of mammography noted by the authors, including overdiagnosis and "false positive" biopsies, are overstated. I am concerned that by overemphasizing the risks of mammography, the authors of this paper are restricting mammographic screening from women who want to minimize their chance of mortality from breast cancer.
Rigorous analysis has shown that overdiagnosis is much lower than the authors state, ranging from 1-10% (1). Furthermore, overdiagnosis differentially affects women of different age groups, increasing with age. Rates vary from less than 1% at age 40, to 30% for DCIS at age 80 (2). Therefore, beginning screening at the age of 40 adds a negligible number of overdiagnosed cases and is not a valid argument to delay screening. Likewise, spacing out screening intervals does not decrease overdiagnosis. If a patient has an indeterminate mass or calcifications detected on a screening exam, delaying that screening exam for 1 year would not have made that finding disappear. The more likely scenario is that the diagnosis and treatment of a breast cancer would have been delayed for an additional year.
The authors do not mention that delaying screening to age 50 actually increases a woman’s chances of having a benign, or "false positive," biopsy compared to initiating at age 40 (3). This was demonstrated in the U.S. Preventive Services Task Force’s data, which also showed little difference between the 10-year cumulative probability of a benign biopsy for annual screening beginning at age 40 (7.0%, or 1 in 143 years) and the probability for biennual screening beginning at age 50 (6.4%, or 1 in 156 years).
Experts in the field of breast cancer weigh the risks of mammography much less than the authors of this paper. And when we ask women, they agree. The vast majority would prefer being called back for additional imaging/biopsy for the chance of having a breast cancer detected earlier (4). I believe that we should not project fear and anxiety onto women with these risks or underestimate their ability to tolerate a few additional views or a percutaneous core biopsy when thousands of lives are at stake.

1. Puliti D, Duffy SW, Miccinesi G et al. Overdiagnosis in mammographic screening of breast cancer in Europe: a literature review. J Med Screen. 2012;19(1):42-56).
2. Hendrick RE. Obligate Overdiagnosis Due to Mammographic Screening: A Direct Estimate for U.S. Women. Radiology. 2018;287(2):391-397.
3. Siu AL et al. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164(4):279-296
4. Ganott MA, Sumkin JH, King JL et al. Screening mammography: do women prefer a higher recall rate given the possibility of earlier detection of cancer? Radiology. 2006;238(3):793-800.
Bethany Niell, MD, PhD12 April 2019
ACP Guideline Will Adversely Impact Older Women Too
It was disheartening to read the American College of Physicians’ Clinical Guideline on screening for breast cancer in average risk women.1 Despite incontrovertible evidence regarding the benefits of annual screening mammography, including in women aged 40-49, the ACP recommends curtailing the use of screening mammography across all age groups.1 Numerous inaccurate and inconsistent statements throughout the guidance statement deserve mention.

Previously submitted comments have not yet addressed Guidance Statement 3, which states “In average-risk women aged 75 years or older or in women with a life expectancy of 10 years or less, clinicians should discontinue screening for breast cancer.”1 The ACP acknowledges that “Age is the single most important risk factor for breast cancer”.1 The age-adjusted incidence of invasive breast cancer is 452 per 100,000 women aged 75-79, which is approximately double the incidence of breast cancer in women aged 50-54 (228 per 100,000).2 In the United States, there were more than 12.2 million women older than 75 years in 2016, and the number is projected to reach 25 million by 2040.3,4 As a result, nearly 1 in 5 breast cancers in the United States is diagnosed in a woman over the age of 75.2 The average life expectancy for a 75 year old woman living in the United States is 12.7-14.6 additional years, depending upon ethnicity.5 Of women who live to age 80, 25% have an estimated life expectancy of 13 years.6 Why does the ACP guideline group all women aged 75 and older with women who have a ≤10 year life expectancy? The decision to stop screening should not be based upon age alone. Screening mammography recommendations for older women should be individualized based upon each woman’s co-morbidities, overall health status, and individual values. Because an average of 3 years is required to prevent one breast cancer death per 5000 women screened (and an average of 10.7 years is required to prevent one breast cancer death per 1000 women screened), it does make sense that women who have a low life expectancy not undergo screening, irrespective of age.7

I suspect that the ACP elected 75 years as the age to stop screening because women aged 75 years and older were excluded from all of the randomized controlled trials of screening mammography. However, observational and modeling studies provide data on the benefits and risks of screening mammography in older women. Older women who regularly undergo screening mammography are 1) more likely to be diagnosed with a smaller node-negative tumor; 2) less likely to die from breast cancer; and 3) less likely to experience the downsides of screening. Older women who do not undergo regular mammography are 3-7-fold more likely to present with late stage disease.8,9 For each mammogram performed, older women are 0.37 times less likely to present with advanced disease.10 Older women who do not undergo regular mammography are 1.6-2.8-fold more likely to die of breast cancer.9,11 The mammographic detection of breast cancers significantly decreases deaths for women over age 75, even in women with mild to moderate levels of comorbid conditions.12 In older women, screening mammography has lower recall rates and higher cancer detection rates, sensitivity, specificity, and positive predictive values, resulting in fewer false positive recalls and false-positive biopsies.13-16 In one study, three different models consistently estimated that the benefits of screening mammography outweigh the risks (including overdiagnosis) until age 90.17

If the ACP believes that the balance of benefits and risks supports screening for women 50–74 years old, the benefits and decreased risks for women over age 75 should also support screening of older women. Unfortunately, the ACP guidance statement is likely to exacerbate the existing under-utilization of screening mammography in older women resulting in unnecessary breast cancer deaths.

References

1. Qaseem A, Lin JS, Mustafa RA, et al: Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med, 2019
2. Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site, April 2018. Accessed April 11, 2019.
3. Roberts, Andrew W., Stella U. Ogunwole, Laura Blakeslee, and Megan A. Rabe, “The Population 65 Years and Older in the United States: 2016,” American Community Survey Reports, ACS-38, U.S. Census Bureau, Washington, DC, 2018.
4. Ortman JM, Velkoff VA, Hogan H. An aging nation:the older population in the United States—current population reports. Washington, DC: U.S. Census Bureau, 2014:25–1140
5. Xu J, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: final data for 2016. National vital statistics reports: vol. 67, no. 5. Hyattsville, MD:
National Center for Health Statistics, 2018
6. Mandelblatt JS, Silliman R: Hanging in the balance: making decisions about the benefits and harms of breast cancer screening among the oldest old without a safety net of scientific evidence. J Clin Oncol 27:487-90, 2009
7. Lee SJ, Boscardin WJ, Stijacic-Cenzer I, et al: Time lag to benefit after screening for breast and colorectal cancer: meta-analysis of survival data from the United States, Sweden, United Kingdom, and Denmark. BMJ 346:e8441, 2013
8. Malmgren JA, Parikh J, Atwood MK, et al: Improved prognosis of women aged 75 and older with mammography-detected breast cancer. Radiology 273:686-94, 2014
9. McCarthy EP, Burns RB, Freund KM, et al: Mammography use, breast cancer stage at diagnosis, and survival among older women. J Am Geriatr Soc 48:1226-33, 2000
10. Badgwell BD, Giordano SH, Duan ZZ, et al: Mammography before diagnosis among women age 80 years and older with breast cancer. J Clin Oncol 26:2482-8, 2008
11. Simon MS, Wassertheil-Smoller S, Thomson CA, et al: Mammography interval and breast cancer mortality in women over the age of 75. Breast Cancer Res Treat 148:187-95, 2014
12. McPherson CP, Swenson KK, Lee MW: The effects of mammographic detection and comorbidity on the survival of older women with breast cancer. J Am Geriatr Soc 50:1061-8, 2002
13. Carney PA, Miglioretti DL, Yankaskas BC, et al: Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography. Ann Intern Med 138:168-75, 2003
14. Hendrick RE, Helvie MA: United States Preventive Services Task Force screening mammography recommendations: science ignored. AJR Am J Roentgenol 196:W112-6, 2011
15. Lee CS, Sengupta D, Bhargavan-Chatfield M, et al: Association of Patient Age With Outcomes of Current-Era, Large-Scale Screening Mammography: Analysis of Data From the National Mammography Database. JAMA Oncol 3:1134-1136, 2017
16. Sinclair N, Littenberg B, Geller B, et al: Accuracy of screening mammography in older women. AJR Am J Roentgenol 197:1268-73, 2011
17. van Ravesteyn NT, Stout NK, Schechter CB, et al: Benefits and harms of mammography screening after age 74 years: model estimates of overdiagnosis. J Natl Cancer Inst 107, 2015
Eric L Rosen11 April 2019
I am concerned about the Screening Guidance Statement From the American College of Physicians
While I agree that the goal of screening is to reduce morbidity and mortality with acceptable tradeoffs, I am concerned by the guidelines published in your journal. 1 Qaseem et al state that there is a low incidence of breast cancer for women younger than 60, yet according to the CDC 98,340/242,476 (41%) cases of invasive breast cancer are diagnosed yearly in women less than 60. Moreover, 28% of breast cancer deaths, almost 12,000, also occur in women less than 60. Since the 1990s breast cancer mortality in the USA has declined by almost 40%, and to me it is unfathomable to recommend a strategy that according to NCI/CISNET breast cancer models would achieve only a 25% mortality reduction. Further, the authors state that overdiagnosis is higher in women aged 40-49, however, an analysis of obligate overdiagnosis, based on the SEER database, demonstrates that screening women 40-49 contributes a negligible 0.1% to the overdiagnosis rate for invasive breast cancer.2 Anyone involved in the care of women with breast cancer knows that the disease in this age group is anything but quiescent. Importantly, less intensive screening will not decrease the frequency of overdiagnosis; a mammographically detectable cancer will remain so, even if screening is delayed or less frequent.3 I further disagree with Qaseem et al’s assertion that the evidence for screening women beginning at age 40 indicates small benefits with substantial harms. CISNET models demonstrate that the greatest mortality reduction is achieved with annual screening of women starting at age 40, with a 71% mortality benefit compared to biennial screening ages 50-74.4 In my opinion, the substantial mortality benefit derived from annual screening starting at age 40 more than offsets the risk posed by additional imaging or a benign needle biopsy. I am not alone, thankfully, as women are well aware of the “risks” associated with screening mammography and consider them worth the benefit.5



References:

1. Qaseem A, Lin JS, Mustafa RA, et al. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med 2019; epub ahead of print.
2. Hendrick RE. Obligate Overdiagnosis Due to Mammographic Screening: A Direct Estimate for U.S. Women. Radiology: 2018 May;287(2):391-397.
3. Sickles EA, Arleo EK, Monticciolo D, Monsees B, McGinty G. Less-Intensive Screening Does Not Reduce the Frequency of Overdiagnosis. J Am Coll Radiol. 2017 Dec;14(12):1520-1522.
4. Arleo EK, Hendrick RE, Helvie MA, Sickles EA. Comparison of recommendations for screening mammography using CISNET models. Cancer. 2017 Oct 1;123(19):3673-3680
5. Schwartz LM, Woloshin S, Sox HC et al. US women's attitudes to false-positive mammography results and detection of ductal carcinoma in situ: cross-sectional survey. West J Med. 2000 Nov;173(5):307-12
Mary S. Newell, MD11 April 2019
Let women decide what constitutes real harm and real benefit
I write to express concern over the methodology used and the conclusions outlined in the ACP screening guidance statement. The statement, created by a committee without specific expertise in breast cancer detection, diagnosis or treatment, is based on a derivative examination of the other groups’ conclusions, rather than its own rigorous assessment of the literature.
Interestingly, using an opaque scoring method, the four reviewed guidelines deemed “high scoring” (ACS, CTFPHC, USPSTF, WHO) are those in alignment with the current ACP position on screening mammography, while those that aren’t were judged to be “low scoring” (ACR, ACOG, NCCN).

An examination of the document reveals biases and inaccurate, misleading information. Consider the second paragraph under Guidance Statement 1:

“ACP concludes that the potential harms of screening for breast cancer with mammography before age 50 years outweigh the benefits in most women.” This statement paternalistically, and without evidence, presents the “harms” and benefits of screening as being equivalent in implication and magnitude. They are not. They are false equivalents, presented as equivalents to justify discouraging women from screening. Most women do not agree with their conclusion [1].

“The absolute risk reduction in breast cancer mortality is lower in women aged 40 to 49 years than in older women.” The Pan-Canadian study showed the same mortality reduction from screening (average: 40%) for women in the 40-49 group as other groups [2].

“Overdiagnosis rates vary across age groups and are higher in women aged 39 to 49 years.” Overdiagnosis is a theoretical concept, its existence and frequency based purely on estimates and assumptions. Since no one can currently predict which, if any, cancers will not progress, its use as a determinate for screening inception and frequency is meaningless.

“Cumulative rates of receiving at least 1 false-positive result and having a biopsy after 10 years are higher for younger women...” The apparent higher rate of false positives is likely a function of women in their 40’s entering the screening process (“prevalence bump”) rather than anything intrinsically unique to this age group, as newly-screened women in the 50’s have similar rates [3]. The cumulative rate is of course higher, by definition, for younger women, but the mortality benefit and life-years gained are higher as well [4].

If we are really striving for shared and informed decision-making by women, let’s let them decide what constitutes real harm and real benefit.

References:
1. Gilliland L et al. Women’s Perspectives on Screening Mammography. ARRS Annual Meeting, April 22-27 2018; Washington DC
2. Coldman A, et al. Pan-Canadian study of mammography screening and mortality from breast cancer. JNCI: Journal of the National Cancer Institute. 2014 Nov 1;106(11).
3. Siu AL. Screening for breast cancer: US Preventive Services Task Force recommendation statement. Annals of internal medicine. 2016 Feb 16;164(4):279-96
4. Mandelblatt JS, et al. Annals of internal medicine 151.10 (2009): 738-747
Jay A. Baker, MD, FACR, FSBI11 April 2019
ACP Guidance Misses the Mark
To the editor:
I read with concern the Guidance Statement from the American College of Physicians (ACP). The goal to “reduce morbidity and mortality, both specific to breast cancer and overall, with acceptable tradeoffs” [1] is laudable, but the actual recommendations fall short.
Restricting screening to women 50-74 and screening every other year instead of annually will clearly increase – not decrease – both morbidity and mortality related to breast cancer. This result is not in question as the U.S. Preventive Services Task Force, on which the ACP relies for its own guidelines, agrees that the most lives are saved by annual screening beginning at age 40 [2]. Women in their 40s are often discounted in screening recommendations because the incidence of breast cancer is lower in these women. However, women in their 40s account for 1-in-6 breast cancer diagnoses, and because of their longer life expectancy, these younger women account for over a quarter of all years of life lost to breast cancer [3]. The data are clear on how to actually reduce the harms caused by breast cancer: according to the NCI-sponsored CISNET computer models, annual screening beginning at age 40 will save 72% more years of life than biennial screening beginning at 50 [3].
Biennial screening starting at 50 also increases – not decreases – the morbidity due to breast cancer. Again, the data are clear: more frequent screening reduces the need for chemotherapy and reduces the need for mastectomies for the 1-in-8 women who will develop breast cancer [4]. The ACP guidelines would lead to more unnecessary chemotherapy and mastectomies for women diagnosed in their 40s in whom screening is devalued by the ACP.
If the goal was to reduce morbidity and mortality due to breast cancer, the ACP missed the mark. Study after study, from computer models to observed outcomes, confirm the morbidity and mortality benefits of starting screening at age 40 and screening every year while the patient is in good health. That the ACP could look at the same data and come to a different conclusion is confusing and regrettable.

Jay A. Baker, MD, FACR, FSBI
Professor, Department of Radiology
Duke University Hospital
[email protected]

Conflict of interest: none

REFERENCES
1. Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ, for the Clinical Guidelines Committee of the American College of Physicians. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of PhysiciansACP Guidance Statement on Breast Cancer Screening in Average-Risk Women. 2019.
2. Siu Al on behalf of the USPSTF. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Int Med. 2016: 164(4); 279-297.
3. Arleo EK, Hendrick RE, Helvie MA, Sickles EA. Comparison of recommendations for screening mammography using CISNET models. Cancer. 2017 Oct 1;123(19):3673-3680.
4. Oeffinger KC, et al; American Cancer Society. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society. JAMA. 2015 Oct 20;314(15):1599-614. doi: 10.1001/jama.2015.12783.
Michelle Lee, MD, Debbie Bennett, MD, Catherine Appleton, MD11 April 2019
Unintended consequences: new ACP breast cancer screening guidance statement marginalizes minorities
We read with great interest and concern the article "Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians." The restricted screening regimen endorsed by the ACP may result in thousands of additional and unnecessary breast cancer deaths each year [1]. Unfortunately, data suggest that this burden will disproportionally be borne by the black community.

Racial disparities in breast cancer mortality are well documented. Black women are 39% more likely to die from breast cancer than white women [2]. Non-white women present at an earlier age than white women, with nearly a third of all breast cancers in non-white women diagnosed before the age of 50 [3]. The incidence of aggressive breast cancers is twice as high in black women compared to white women [4].

Reducing the disparity gap requires providing women with access to screening mammography at the appropriate age and frequency. The ACP’s conclusion that the “potential harms outweigh the benefits in most women aged 40 to 49 years” does not take into consideration the epidemiology of breast cancer for non-white women. The incidence of breast cancer for black women peaks in their 40s [3]; this is therefore a critical time to screen for cancers, before regional or metastatic spread occurs.

As physicians in St. Louis, where almost half of our city’s women are black [5], reducing the disparity in breast cancer mortality is a responsibility we take very seriously. Although we support efforts to provide “clarity and simplicity,” the ACP’s guidance statement discounts important considerations that will likely have the unfortunate consequence of widening an already sizeable breast cancer mortality gap between white and black women.


References:
1. Hendrick RE and Helvie MA. United States Preventive Services Task Force Screening Mammography Recommendations: Science Ignored. AJR. 2011;196:W112-W116.
2. DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439-48.
3. Stapleton SM, Oseni TO, Bababekov YJ, Hung YC, Chang DC. Race/Ethnicity and Age Distribution of Breast Cancer Diagnosis in the United States. JAMA Surg. 2018;153(6):594-5.
4. Hunt BR, Whitman S, Hurlbert MS. Increasing Black:White disparities in breast cancer mortality in the 50 largest cities in the United States. Cancer Epidemiol. 2014;38(2):118-23.
5. U.S. Census Bureau, www.census.gov, acessed 10 April 2019



Michelle V. Lee, MD
Assistant Professor of Radiology, Program Director Breast Imaging Fellowship
Mallinckrodt Institute of Radiology
Washington University School of Medicine
510 S. Kingshighway Blvd.
St. Louis, MO 63110
[email protected] 314-454-7696

Debbie L. Bennett, MD
Assistant Professor of Radiology, Section Chief of Breast Imaging
Medical Director for SSM Health St. Louis Breast Imaging
Saint Louis University School of Medicine
3635 Vista Blvd.
St. Louis, MO 63110
[email protected] 314-268-5782

Catherine M. Appleton, MD
Chief Breast Imaging Section
Associate Professor of Radiology
Mallinckrodt Institute of Radiology
Washington University School of Medicine
510 S. Kingshighway Blvd.
St. Louis, MO 63110
[email protected] 314-454-7696
Stamatia Destounis, MD11 April 2019
New ACP screening mammography guidelines overstate the presence of overdiagnosis
The breast cancer screening guidelines for women at average risk released by the American College of Physicians (ACP) [1] recommend biennial screening for women 50-74, steering physicians away from the lifesaving practice of annual screening beginning at age 40, a screening schedule that is proven to reduce mortality in all age groups, including women under 50. The new guidelines are fraught with misleading and biased statements which overstate the harms of screening, specifically overdiagnosis.
The authors describe that an association between screening and overdiagnosis has been demonstrated in many studies, citing a particularly high rate (22%), while acknowledging that estimates vary substantially in the literature [1]. It is difficult to measure the rate of overdiagnosis, and studies that cite high rates fail to properly adjust for lead time, risk factors, and trends in the background incidence [2]. Estimates adjusted for lead time range from 1.0% to 10% [3] Due to difference in life expectancy, overdiagnosis is more likely to affect older women, rather than younger women. The authors do not consider this, nor that (if overdiagnosis is true), it will not go away by delaying screening to age 50. Breast cancers do not spontaneously disappear or regress [4]. Therefore deferring screening to age 50 would lead to delayed diagnosis, allowing breast cancers to grow larger and possibly spread to the blood or lymph system, all of which results in the need for more extensive treatment for the patient. The authors also do not consider the patients’ point of view; when asked about the impact of overdiagnosis on their desire to attending screening, women felt rates had limited impact on their commitment to screening, and that the potential for overdiagnosis was acceptable due to the benefits of early detection [5].
The purpose of screening mammography is to detect tumors when they are small, with less nodal involvement, and lower stage. As doctors it is our job to communicate the optimal screening regimen for our patients, to allow our patients the highest chance of early detection and mortality reduction, while providing a balanced assessment of the both the potential harms and life-saving benefits. Overdiagnosis should not factor into this. All major organizations do agree that annual mammography screening beginning at the age of 40 saves the most lives.

1. Qaseem A, Lin JS, Mustafa RA, et al. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med 2019; epub ahead of print. doi:10.7326/M18-2147
2. Ray KM, Joe BN, Freimanis RI, Sickles EA, Hendrick RE. Screening Mammography in Women 40-49 Years Old: Current Evidence. AJR 2018; 210: 264-270.
3. Puliti D, Duffy SW, Miccinesi G, et al. Overdiganosis in mammographic screening for breast cancer in Europe: a literature review. J Med Screen 2012; 19 Suppl 1: 42-56.
4. Arleo EA, Monticciolo DL, Monsees B, McGinty G, Sickles EA. Persistent Untreated Screening-Detected Breast Cancer: An Argument Against Delaying Screening or Increasing the Interval Between Screenings. JACR 2017; 14(7): 863-867.
5. Hersch J, Jansen J, Barratt A, et al. Women’s views on overdiagnosis in breast cancer screening: a qualitative study BMJ 2013; 346: f158
Georgia Giakoumis Spear, MD10 April 2019
Delaying Screening Will Do More Harm than Good
With interest, I read the ACP guidance statement, but the proposed guidelines are predicated on assumptions that perceived harms of screening, namely patient anxiety, outweigh the undeniable life-saving benefit of annual screening, isolating women ages 40-49 and stripping their right to life saving benefits from screening. It is our duty to care for our patients and do no harm, and the proposal by the ACP will clearly harm women by confusing them with misinformation resulting in an increase in breast cancer deaths.

I am concerned by the omission of data that shows over a 40% reduction in breast cancer mortality across all age groups (40-84) (4). Meta-analysis of CISNET/NCI shows annual screening saves 71% more lives than biennial screening in women 50-74 (1). Women 40-49 will suffer an additional 100,000 lives lost with ACP’s screening regimen. The ACP guidance is also contradictory to data acknowledged by the ACS and USPSTF, that maximum mortality benefits are achieved with annual screening beginning at the age of 40 (1).

Looking closer at the science, just less than half (42%) of diagnosed invasive breast cancers occur in women 40-59 years of age (2). Annual screening in the 40-49 year old group identifies cancers an estimated 2 years before they would become clinically apparent (4). If these cancers are left undiagnosed, we will assuredly see the effects of advanced stage disease and increased mortality from breast cancer.

The harms, as addressed by the article, cannot arguably be compared to the increase in deaths due to breast cancer that would result from the delay in screening proposed by the ACP regimen. Can perceived risks of patient anxiety resulting from being called back for a few additional mammographic views, an ultrasound, or even a 2% risk of a needle biopsy, outweigh the significant decrease in mortality benefit from breast cancer screening? Overdiagnosis rates of 2-10% have been published; rates that are small, if not negligible, compared to the mortality benefit achieved with screening (3,4). It would be unconscionable to support a screening regimen that would cause more harm than good.
The ACS, USPSTF, ACR and SBI all agree that “if a woman would like to achieve maximum life saving benefits from screening, annual screening mammography is recommended to begin at the age of 40.”


1. Hendrick RE, Helvie MA. United States Preventive Services Task Force Screening Mammography Recommendations: Science Ignored. American Journal of Roentgenology 2011 196:2, W112-W116
2. American Cancer Society. Breast Cancer Facts & Figures 2017-2018. Atlanta: American Cancer Society, Inc. 2017.
3. Puliti D, Duffy SW, Miccinesi G, de Koning H, Lynge E, Zappa M, Paci E. Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review. J Med Screen 2012; 19 (suppl 1):42–56
4. Monticciolo D, Helvie M, HEndrick RE. Current Issues in the Overdiagnosis and Overtreatment of Breast Cancer. American Journal of Roentgenology 2018; 210:2, 285-291
Daniel Kopans, M.D.10 April 2019
REALLY??!!
REALLY?!!
The Annals/ACP “Guidance document” on breast cancer screening (1) is packed with misinformation. Breast cancer is the second leading cause of cancer death (lung cancer is the first) among women, not the “fourth”. And it goes downhill from there. The bottom line is that the ACP is advising women to delay screening until age 50 and to then be screened every two years despite the fact that everyone agrees (including the ACP and the USPSTF), and the evidence proves, that the most lives are saved by screening starting at the age of 40. The “Guidance” document implies that the “harms” of “overdiagnosis” and “overtreatment” would be reduced by delaying screening. This would require that the “fake”, mammographically detected breast cancers that have been falsely postulated by scientifically unsupportable analyses (2), will disappear if left undetected. The problem is that no one has ever seen this happen. In a review of almost 500 breast cancers found by mammography that were not treated, not a single one disappeared or even regressed (3). This means that if you wait until age 50 and screen every two years, the “fake” (“overdiagnosed”) cancers (if they even exist) will still be there. There will be no effect on “overdiagnosis” and consequently no effect on “overtreatment”. The only “harm” that will be reduced by delaying screening is the recall rate (pejoratively termed “false positives”) where women are recalled for a few extra pictures or an ultrasound and most are told everything is fine. Approximately 2% of women will be advised to have an imaging guided needle biopsy using local anesthesia (very safe) and 20-40% will be found to have breast cancer (a high yield) at a time when cure is likely.
The National Cancer Institute sponsored Cancer Intervention and Surveillance Modeling Network (CISNET) has shown that if women now in their thirties, wait until the age of 50 to be screened every two years, as many as 100,000 will die, unnecessarily, whose lives could be saved by annual screening starting at the age of 40 (4). What the ACP has now decided is that they are willing to allow (advise) tens of thousands of women to die unnecessarily, just to reduce the “recall” rate and a few, very safe, needle biopsies. REALLY?!!!
1. Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Annals of Int Med 2019
2. Kopans DB. Arguments Against Mammography Screening Continue to be Based on Faulty Science. The Oncologist 2014;19:107–112
3. Arleo EK, Monticciolo DL, Monsees B, McGinty G, Sickles EA. Persistent untreated screening-detected breast cancer: an argument against delaying screening or increasing the interval between screenings. J Am Coll Radiol 2017; 14:863-867.
4. Hendrick RE, Helvie MA. USPSTF Guidelines on Screening Mammography Recommendations: Science Ignored. Am. J. Roentgenology 2011; 196: W112 - W116.
Peter R Eby, MD, FACR10 April 2019
Deaths of 40-49 year old women account for 27% of all life-years lost to breast cancer.
The burden of breast cancer on 40-49 year old women and their families is disproportionate. They account for 17% of all diagnoses and deaths while losing 27% of all years of life to breast cancer (1). Despite these simple facts, the American College of Physicians (ACP) has issued stunning guidelines, without reviewing any new data, which paternalistically exclude women in their 40s from participating in breast cancer screening (2). Research and CISNET modeling confirm that getting a mammogram every year starting at 40, as recommended by the American Congress of Obstetricians and Gynecologists and National Comprehensive Cancer Network, will save the most lives from breast cancer. (3) The United States Preventive Services Task Force, American Cancer Society and American College of Radiology all agree on this point. (1) While any death from breast cancer is difficult, the deaths of women in their 40s, who are often otherwise healthy and have many vibrant years ahead, are especially heartbreaking. Despite these important factors, the ACP is recommending screening mammograms every other year starting at age 50. This will result in women of all ages discovering breast cancer later when it is more advanced, more costly to treat and harder to beat. If these recommendations are followed, approximately 6500 women in the United States will die unnecessarily each year from breast cancer. (4) The purpose of the ACP guidance statement is “…to assist clinicians in making decisions about breast cancer screening in asymptomatic women…” (1) Clinicians make the decisions in this framework. Sadly, the ACP has lost sight of the patients they serve. The new guidance statement leaves 40-49 year old women out of the decision making process. There is no need for the ACP to compromise and risk the lives of young women. The policy that saves the most lives and allows women to choose if they want to participate is to recommend screening mammograms every year starting at 40.


1. Oeffinger KC, et al; American Cancer Society. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society. JAMA. 2015 Oct 20;314(15):1599-614. doi: 10.1001/jama.2015.12783.
2. Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ; Clinical Guidelines Committee of the American College of Physicians. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med. 2019 Apr 9. doi: 10.7326/M18-2147. [Epub ahead of print] PMID: 30959525
3. Mandelblatt JS, Stout NK, Schechter CB, van den Broek JJ, Miglioretti DL, Krapcho M, et al. Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies. Ann Intern Med. 2016 Feb 16;164(4):215-25. doi: 10.7326/M15-1536. Epub 2016 Jan 12. PMID: 26756606
4. R. Edward Hendrick and Mark A. Helvie. United States Preventive Services Task Force Screening Mammography Recommendations: Science Ignored American Journal of Roentgenology 2011 196:2, W112-W116
Kelly W Biggs, MD10 April 2019
ACP guidelines ignore decades of evidence in support of screening mammography beginning age 40
The ACP concludes “that the potential harms of screening for breast cancer with mammography before the age of 50 years outweigh the benefits in most women,” citing “anxiety, distress, and worry” among its chief harms. Women should know that these so called harms must be measured against evidence accrued over decades that proves mammograms save lives in the age 40-49 group. Randomized Controlled Trials demonstrate a reduction in breast cancer deaths for women in this age group who participate in screening.[1] This is corroborated by observational studies such as the recent Pan-Canadian study, which demonstrated a 44% reduction in breast cancer deaths for women who screened in the 40-49 group.[2] A recent study in the journal Cancer concluded that about 70% of breast cancer deaths among women in their 40s occurred in the 20% who did not undergo screening.[3] To discourage a woman from breast cancer screening in order to reduce stress is faulty logic at best.
References
1. Hendrick RE, et al. “Benefit of screening mammography in women aged 40-49: a new meta-analysis of randomized controlled trials.” J Natl Cancer Inst Monogr; 1997;(22):87-92
2. Coldman, Phillips, Wilson, et al. “Pan-Canadian Study of Mammography Screening and Mortality from Breast Cancer” J Natl Cancer Inst. 2014 Oct 1;106(11)
3. Webb ML, Cady B, Michaelson JS, et al. “A failure analysis of invasive breast cancer: Most deaths from disease occur in women not regularly screened.” Cancer. 2014; 120 (18): 2781-2938.
Donna Plecha, MD10 April 2019
Harms of the ACP guidelines
I agree with the authors of the article that the “goal of screening is to reduce morbidity and mortality,” however I disagree with their assumptions which invalidates their conclusions. Multiple randomized controlled and observational trials have proven that screening mammography reduces mortality 15-40% in women 40-74 years of age. In order to save the most lives, the United States Preventive Task Force and the American Cancer Society agree that starting at the age of 40 with annual screening saves the most lives[1]. Similar to other screening tests, mammography is not perfect and has associated false positive results and benign biopsies associated with it. However the authors did not consider the actual harm of not screening annually starting at the age of 40 which leads to the loss of 71% more lives if the ACP recommendations are followed[2]. In addition, recent studies have shown that the use of digital breast tomosynthesis can reduce the false positive recall rate by 15% compared to digital mammography, demonstrating advances in technology have helped to reduce the perceived harms of false positives associated with screening for breast cancer[3].

In the ACP recommendations there is more weight given to the short term harms of false positives and benign biopsies than on the positive impact screening with mammography has on reducing the morbidity from breast cancer and its treatment. Mammography detects more breast cancers at an earlier stage, smaller size and that are more likely to be lymph node negative. Because of the earlier detection the breast cancers are easier to treat. Patients with breast cancer found with screening mammography are much less likely to undergo mastectomy and chemotherapy[4,5]. The long lasting toxic harms of more aggressive treatment have a much larger and longer impact on a patient’s life than a negative biopsy or additional imaging to insure a patient does not have cancer.

Minimizing the positive life-saving impact of screening and not considering its positive impact on the morbidity are shortcomings of the ACP recommendations, bringing their conclusions into question. Unfortunately these recommendations will lead to more lives lost to breast cancer, and more patients with long lasting side effects of more aggressive therapies. Women should have valid and complete facts so they can make informed decisions about their health care.





1. Monticciolo, D.L., et al., Breast Cancer Screening for Average-Risk Women: Recommendations From the ACR Commission on Breast Imaging. J Am Coll Radiol, 2017. 14(9): p. 1137-1143.
2. Hendrick, R.E. and M.A. Helvie, United States Preventive Services Task Force screening mammography recommendations: science ignored. AJR Am J Roentgenol, 2011. 196(2): p. W112-6.
3. Friedewald, S.M., et al., Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA, 2014. 311(24): p. 2499-507.
4. Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst M. Influence of tumour stage at breast cancer detection on survival in modern times: population based study 173,797 patients. BMJ 2015; 351:h4901.
5. Plecha, D., et al., Neglecting to screen women between 40 and 49 years old with mammography: what is the impact on treatment morbidity and potential risk reduction? AJR Am J Roentgenol, 2014. 202(2): p. 282-8.
Amanda Lenderink-Carpenter MD10 April 2019
Overdiagnosis rates higher in younger women?
I read the article by Qaseem et al (1) and whole-heartedly agree with their statement “Physicians play a key role in helping women accurately sort through the clinical evidence.” Unfortunately the paper has left us ill-equipped to perform that role. The ACP emphasizes that the overdiagnosis rates are higher in women age 39-49. That statement certainly causes one to take pause. We know that women in their 40s are more likely to have biologically aggressive cancers. We also know that women in their 40s have far more life years remaining, resulting in more time for a small or slower growing cancer to become clinically relevant and life threatening. Women in their 40s have many more years to live and contribute to society. They are citizens in mid-career, climbing the ladder to make lasting contributions. They are moms of young children, raising the future generation. Are we then to sit down with these women and tell them “mammography may not be the best option at your age because of the chance it will find a cancer that won’t actually cause a problem in your lifetime”? When savvy patients respond with “Why won’t those cancers be a problem when I turn 50?” What is the appropriate answer? It’s a tricky place to be, and its hard question to answer because we know based just on logic, that it doesn’t make sense. To the authors' credit, they did discuss that modeling studies demonstrate much lower rates of overdiagnosis. In fact, the modeling studies actually represent the most accurate assessment of overdiagnosis because they account for trends in breast cancer incidence and lead time; two factors which are critically important when evaluating any screening test. (2,3) These modeling studies accurately show that the over diagnosis rate in women 40-49 is essentially zero. (2) This very basic assumption calls into question the conclusion that “the potential harms outweigh the benefits for most women aged 40-49 years.”

References
1. Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ, Clinical Guidelines Committee of the
American College of Physicians. Screening for Breast Cancer in Average-Risk Women: A
Guidance Statement From the American College of Physicians. Ann of Internal Medicine. 2019 April.
2. Hendrick RE. Obligate Overdiagnosis Due to Mammographic Screening: A Direct Estimate for US Women. Radiology. 2018 May; 287(2)391-397
3. Monticciolo D, Helvie M, Hendrick RE. Current Issues in the Overdiagnosis and Overtreatmetn of Breast Cancer. AJR. 2018, February; 210(2): 285-291
Lars Grimm10 April 2019
The need for true shared decision making in screening guidelines
I read with great interest the article by Qaseem et al on the new breast cancer screening guidelines for average risk women and was pleased by the strong emphasis placed on shared decision (1). Shared decision making is one of the great advances of modern medicine that has shifted healthcare away from the paternalistic model of the past, towards a new model that educates and empowers patients to actively engage in their healthcare decisions. Unfortunately, I worry that the narrative of these guidelines has created a false choice for patients that may do more harm than good.

The guidelines state that, “in average-risk women aged 40 to 49 years, clinicians should discuss whether to screen for breast cancer with mammography,” thereby encouraging engagement and emphasizing patient values. For this approach to be successful, patients must be presented with evidence in an unbiased fashion that can be internalized. Unfortunately, the new guidelines immediately place a value judgement on this decision by stating that, “the potential harms outweigh the benefits in most women aged 40 to 49 years.”

The authors cite that both the ACS and the WHO found statistically significant benefits to breast cancer-associated mortality for women aged 39 to 49 (2, 3), but then dismiss the value of these findings by citing wide ranges of overdiagnosis (0 to 54%), a higher risk of having a false-positive mammograms and biopsies, and radiation induced breast cancers. Instead, a patient-centric approach would emphasize that a 40 year old woman has approximately 43 more years of life left to live and that a breast cancer diagnosed in the 40s is more likely to be biologically aggressive and harder to treat unless found quickly (4). Furthermore, any discussion of ‘risks’ should be personalized. For women aged 40-49, these ‘risks’ include a recall for a diagnostic workup every 12 years, a negative biopsy every 149 years, and a radiation-induce breast cancer every 97,000 years.

As physicians, we all want the best for our patients, but in the era of shared decision making it is critical to present information to our patients in a personalized fashion without value judgments. Instead, the ACP guidelines have de-emphasized the lives saved by screening women in their 40s and not provided appropriate context for women to be active healthcare partners.

1. Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ, for the Clinical Guidelines Committee of the American College of Physicians. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of PhysiciansACP Guidance Statement on Breast Cancer Screening in Average-Risk Women. 2019.
2. World Health Organization 2014;Pageswww.who.int/cancer/publications/mammography_screening/en on January 18, 2018.
3. Myers ER, Moorman P, Gierisch JM, Havrilesky LJ, Grimm LJ, Ghate S, et al. Benefits and Harms of Breast Cancer Screening: A Systematic Review. JAMA. 2015;314(15):1615-34.
4. Centers for Disease Control and Prevention 2015;Pageshttps://www.cdc.gov/nchs/data/nvsr/nvsr67/nvsr67_07-508.pdf on April 9, 2019.
Anna Holbrook, MD10 April 2019
Recommendations will lead to unnecessary deaths in women of color
I read with great concern the article “Screening for breast cancer in average-risk women: a guidance statement from the American College of Physicians [1].” If these recommendations are followed, countless women of color will die preventable deaths.

The authors promote mammographic screening beginning at age 50, and state that the harms of mammography outweigh the benefits in women aged 40 to 49. However, black, Hispanic and Asian women have a peak incidence of breast cancer in their forties [2]. These recommendations would therefore exclude these women from lifesaving screening.

The authors also recommend biennial, rather than annual, screening. As cancers in black women tend to be more aggressive than those in whites, early detection is the key to survival, and more frequent screening is critical [3].

Black women already suffer from higher breast cancer mortality rates when compared to whites [4]. Following these guidelines would only make the discrepancy worse. I highly recommend beginning screening at age 40 and screening annually. Assessment of risk status should be done even earlier, by age 30.

1. Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med. Apr 9 2019.
2. Stapleton SM, Oseni TO, Bababekov YJ, Hung YC, Chang DC. Race/Ethnicity and Age Distribution of Breast Cancer Diagnosis in the United States. JAMA Surg. Jun 1 2018;153(6):594-595.
3. Martin N, Wingfield J. USPSTF screening recommendations for breast cancer: the potential impact on the African American community. J Health Care Poor Underserved. May 2012;23(2 Suppl):91-97.
4. Hunt BR, Hurlbert MS. Black:white disparities in breast cancer mortality in the 50 largest cities in the United States, 2005-2014. Cancer Epidemiol. Dec 2016;45:169-173.
Sharp F. Malak, MD, MPH10 April 2019
ACP Breast Cancer Screening Guidelines Overlook Race and will Widen the Mortality Disparity Gap.
As a Breast Cancer Epidemiologist, it was with great interest that I read the ACP breast cancer screening guidelines. Increasing health care equity is advocated by the ACP, but these guidelines ignore the impact of race with regard to breast cancer screening and mortality. Non-Hispanic African-American women are 40% more likely to die of breast cancer than Non-Hispanic White women despite having the same incidence of breast cancer [1]. While the fixed factors of tumor biology and genomics contribute to this mortality disparity, Public Health advocates can use the time critical power of secondary prevention (screening mammography) to narrow the mortality disparity [2]. 22% of the African-American women diagnosed with breast cancer are less than 50 years old [3], but the ACP guidelines ignore this age distribution and recommend screening beginning at the age of 50. Delaying screening until the age of 50 unnecessarily jeopardizes the lives of thousands of women and will exacerbate the breast cancer mortality disparity that painfully exists in the US and so many in Public Health are attempting to eliminate. The largest reduction in mortality and most life-years gained occur when women undergo annual screening mammography beginning at the age of 40 [4].

References

1. American Cancer Society. Breast Cancer Facts & Figures 2017-2018. Atlanta: American Cancer Society, Inc. 2017.
2. Grabler, P., et al., Regular screening mammography before the diagnosis of breast cancer reduces black:white cancer differences and modifies negative biological prognostic factors. Breast Cancer Res Treat (2012) 135:549-553.
3. U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on November 2017 submission data (1999-2015): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; www.cdc.gov/cancer/dataviz, June 2018.
4. Arleo, E.K., et al., Comparison of Recommendations for Screening Mammography Using CISNET Models. Cancer, 123:3673-3680.
Robert L. Gutierrez, MD, FSBI9 April 2019
All-cause Mortality Benefit Ignored by the ACP Guidelines
In their screening guidelines, the ACP states that “individual studies were not designed to assess all-cause mortality,” referring to screening mammography RCTs. Although this is a true statement, as the original RCTs were not statistically powered to demonstrate an all-cause mortality benefit, it falls short of painting a complete and accurate picture. In their fervor to discount the well-documented life-saving benefits of screening mammography, the ACP failed to mention relevant and compelling work such the Swedish Two-county trial that demonstrated an all-cause mortality benefit in patients invited to participate in screening [1] or more recently a study from the Marshfield Clinic Health System that showed a similar benefit among patients in a large multispecialty group practice in the United States [2]. This oversight is one example among many in their guidelines that underscores the ACPs intent of casting screening mammography in a negative light. The development of screening guidelines is a critical task that carries with it life and death consequences for our patients. Unfortunately, the ACP guidelines point their providers in the wrong direction and will result in thousands of preventable deaths from breast cancer.


References:

1. Tabár L, Duffy SW, Yen MF, et al. All-cause mortality among breast cancer patients in a screening trial: support for breast cancer mortality as an end point. J Med Screen 2002; 9:159–162
2. Engle JM, Stankowski-Drengler TJ, Stankowski RV, et al. All-Cause Mortality Is Decreased in Women Undergoing Annual Mammography Before Breast Cancer Diagnosis. American Journal of Roentgenology 2015 204:4, 898-902
Elizabeth Kagan Arleo MD9 April 2019
ACP Guidance Statement 2 should be revised to promote annual screening mammography starting at age 40
If the American College of Physicians (ACP) is truly “a diverse community of internal medicine specialists and subspecialists united by a commitment to excellence” [1], then the organization should revise guidance statement 2 of their new breast cancer screening article recommending “in average-risk women aged 50-74 years, clinicians should offer screening for breast cancer with biennial mammography” [2]. The rationale for revision? This current guidance statement is only associated with a 23% reduction in breast cancer specific mortality, compared with annual screening mammography starting at age 40, which is associated with a 39.6% reduction in breast cancer specific mortality [3]. As is stands, the current ACP guidance statement for biennial screening with a delayed start age and premature end is far from the excellence the ACP states it is committed to achieving.

References
1. American College of Physicians (ACP). Who We Are. Accessed May 8, 2019. https://www.acponline.org/about-acp/who-we-are
2. Qaseem A, et al. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med. 9 April 2019.
3. Arleo EK, Hendrick RE, Helvie MA, Sickles EA. Comparison of recommendations for screening mammography using CISNET models. Cancer. 2017 Oct 1;123(19):3673-3680.

Disclosures: Editor-in-Chief, Clinical Imaging

Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 170Number 816 April 2019
Pages: 547 - 560

History

Published online: 9 April 2019
Published in issue: 16 April 2019

Keywords

Authors

Affiliations

Amir Qaseem, MD, PhD, MHA
American College of Physicians, Philadelphia, Pennsylvania (A.Q.)
Jennifer S. Lin, MD, MCR
Kaiser Permanente Northwest, Portland, Oregon (J.S.L.)
Reem A. Mustafa, MD, MPH, PhD
University of Kansas Medical Center, Kansas City, Kansas (R.A.M.)
Carrie A. Horwitch, MD, MPH
Virginia Mason Medical Center, Seattle, Washington (C.A.H.)
Timothy J. Wilt, MD, MPH
Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota (T.J.W.)
for the Clinical Guidelines Committee of the American College of Physicians
Note: Guidance statements are “guides” only and may not apply to all patients and all clinical situations. Thus, they are not intended to override clinicians' judgment. All ACP guidance statements are considered automatically withdrawn or invalid 5 years after publication, or once an update has been issued.
Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations.
Acknowledgment: The Clinical Guidelines Committee thanks members of the ACP Guidelines Public Panel for their review and comments on the paper from a nonclinician, public perspective: Cynthia Appley, Larry Curley, Jane Eleey, Ray Haeme, James Pantelas, Missy Carson Smith, and Lelis Vernon.
Financial Support: Financial support for the development of this guidance statement comes exclusively from the ACP operating budget.
Disclosures: Dr. Mustafa has served as a site principal investigator for a randomized controlled trial funded by Boehringer Ingelheim and subcontracted through Duke University since 2019. Authors followed the policy regarding conflicts of interest described at www.annals.org/article.aspx?articleid=745942. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-2147. All financial and intellectual disclosures of interest were declared, and potential conflicts were discussed and managed. Dr. Humphrey was recused from voting because of a moderate-level conflict (recipient of a university-funded grant and author of several recent publications related to the topic); Dr. Manaker was recused from discussion and voting because of a high-level conflict (household member owns stock in industry). A record of disclosures of interest and management of conflicts of interest is kept for each Clinical Guidelines Committee meeting and conference call and can be viewed at www.acponline.org/clinical_information/guidelines/guidelines/conflicts_cgc.htm.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Correction: After publication of this article, Dr. Mustafa disclosed a high-level conflict of interest that was previously not reported by her (she has served as a site principal investigator for a randomized controlled trial funded by Boehringer Ingelheim and subcontracted through Duke University since 2019). The CGC considers any active relationship with drug companies a high-level conflict of interest, regardless of whether the interest is clinically relevant to the guideline topic. The CGC policy is to not include individuals with potential conflicts of interest as guideline authors. This article was corrected on 14 February 2023 to include updated disclosure forms for Dr. Mustafa. An erratum has been published (doi:10.7326/L23-0043).
Corresponding Author: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, [email protected].
Current Author Addresses: Dr. Qaseem: 190 N. Independence Mall West, Philadelphia, PA 19106.
Dr. Lin: 3800 North Interstate Avenue, Portland, OR 97227.
Dr. Mustafa: 3901 Rainbow Boulevard, MS3002, Kansas City, KS 66160.
Dr. Horwitch: 1100 Ninth Avenue, C8-GIM, Seattle, WA 98101.
Dr. Wilt: VA Medical Center 111-0, Minneapolis, MN 55417.
Author Contributions: Conception and design: A. Qaseem, R.A. Mustafa, T.J. Wilt.
Analysis and interpretation of the data: A. Qaseem, J.S. Lin, R.A. Mustafa, T.J. Wilt.
Drafting of the article: A. Qaseem, R.A. Mustafa, C.A. Horwitch, T.J. Wilt.
Critical revision of the article for important intellectual content: A. Qaseem, J.S. Lin, R.A. Mustafa, T.J. Wilt.
Final approval of the article: A. Qaseem, J.S. Lin, R.A. Mustafa, C.A. Horwitch, T.J. Wilt.
Statistical expertise: A. Qaseem, T.J. Wilt.
Administrative, technical, or logistic support: A. Qaseem, T.J. Wilt.
Collection and assembly of data: A. Qaseem, T.J. Wilt.
This article was published at Annals.org on 9 April 2019.
* This paper, authored by Amir Qaseem, MD, PhD, MHA; Jennifer S. Lin, MD, MCR; Reem A. Mustafa, MD, MPH, PhD; Carrie A. Horwitch, MD, MPH; and Timothy J. Wilt, MD, MPH, was developed for the Clinical Guidelines Committee of the American College of Physicians. Individuals who served on the Clinical Guidelines Committee from initiation of the project until its approval were Mary Ann Forciea, MD† (Chair); Nick Fitterman, MD†; Carrie A. Horwitch, MD, MPH†; Linda L. Humphrey, MD, MPH‡; Alfonso Iorio, MD, PhD†; Devan Kansagara, MD, MCR†; Jennifer S. Lin, MD, MCR†; Scott Manaker, MD, PhD§; Michael Maroto, JD, MBA†||; Robert M. McLean, MD†; Reem A. Mustafa, MD, MPH, PhD†; Janice E. Tufte†||; Sandeep Vijan, MD, MS†; and Timothy J. Wilt, MD, MPH†. Approved by the ACP Board of Regents on 21 July 2018.
† Author (participated in discussion and voting).
‡ Nonauthor contributor (participated in discussion but excluded from voting).
§ Recused from participation because of a conflict of interest.
|| Nonclinician public representative.

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Amir Qaseem, Jennifer S. Lin, Reem A. Mustafa, et al; for the Clinical Guidelines Committee of the American College of Physicians . Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med.2019;170:547-560. [Epub 9 April 2019]. doi:10.7326/M18-2147

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