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

Elizabeth Kagan Arleo MD

NY Presbyterian / Weill Cornell

April 8, 2019

Conflict of Interest: Editor-in-Chief, Clinical Imaging

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.

Robert L. Gutierrez, MD, FSBI

Kaiser Permanente Washington

April 9, 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

Kelly W Biggs, MD

Tyrone Hospital, PA

April 10, 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, MD

University Hospitals Cleveland

April 10, 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 MD

Kaiser Permanente

April 10, 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 Grimm

Duke University

April 9, 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, MD

Emory University

April 9, 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, MPH

University of Arkansas for Medical Sciences

April 9, 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.

Daniel Kopans, M.D.

Harvard Medical School

April 10, 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.

Georgia Giakoumis Spear, MD

NorthShore University HealthSystem/The University of Chicago

April 10, 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

Peter R Eby, MD, FACR

Virginia Mason Medical Center

April 10, 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

Eric L Rosen

University of Colorado

April 11, 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, MD

Emory University SOM

April 11, 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, FSBI

Duke University Hospital

April 10, 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
Jay.Baker@Duke.edu

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, MD

Washington University in St. Louis, Saint Louis University

April 10, 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
leemi@wustl.edu 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
debbie.bennett@health.slu.edu 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
appletonc@wustl.edu 314-454-7696

Stamatia Destounis, MD

Elizabeth Wende Breast Care, Clinical Professor University of Rochester, Rochester NY

April 10, 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

Aya Michaels, MD

NY Presbyterian Hospital/ Weill Cornell

April 12, 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, PhD

H. Lee Moffitt Cancer Center

April 11, 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

Jiyon Lee MD, Paula B. Gordon MD, Vilert Loving MD

NYU School of Medicine, University of BC, Banner MD Anderson Cancer Center

April 15, 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. Friedewald

Northwestern Medicine, Northwestern University

April 12, 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

Dipti Gupta

Northwestern Memorial Hospital

April 15, 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.

Margaret Fleming, MD, MSc

Emory University School of Medicine

April 18, 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
mflem01@emory.edu

Conflicts of interest: None

Lora D. Barke DO, Luke Hoagland MD

Radiology Imaging Associates

April 19, 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.

William T. Phillips, Ralph Blumhardt

University of Texas Health Science Center at San Antonio

April 29, 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

Jennifer S. Lin, MD, MCR, Reem A. Mustafa, MD, MPH, Timothy J. Wilt, MD, MPH, Carrie A. Horwitch, MD, MPH, Amir Qaseem, MD, PhD, MHA

American College of Physicians

July 18, 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.

Richard Fleming, PhD, MD, JD

FHHI-OI-Camelot

October 18, 2019

Conflict of Interest: FMTVDM issued to author.

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.