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Breast Cancer Screening: When to Begin?

Alison Chetlen, DO and Neda Frayha, MD
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PC RAP has covered the start-screening-mammos-at-age-50 perspective in the past. Today, we’ll explore the other side of the coin: why women’s health focused organizations recommend beginning annual screening mammography at age 40. Neda sat down with Dr. Alison Chetlen, breast imaging expert and Associate Professor and Vice Chair of Education in the Department of Radiology at Penn State Health and Hershey Medical Center, for a deeper dive into the evidence we don’t always hear about in primary care. 

Pearls:

  • Dr. Chetlen leans into earlier annual mammography at age 40 given:

    • Improved technology (radiography and cancer treatment) since the time of the randomized control trials that societies still use to develop guidelines

    • Seriously flawed data from a  Canadian trial that influenced USPSTF guidelines

    • New studies that have long-term follow-up showing clear mortality benefit from earlier screening

 

  • Goals of screening to reduce deaths from breast cancer by:

    • Detecting earlier when smaller and when more effective to treat

      • If a woman waits until the cancer is palpable, usually it is larger and more likely to have spread to the lymph nodes (especially for premenopausal women)

    • Largest and longest running breast cancer trials found that the annual mammography screening cuts breast cancer deaths by ⅓ in all women ages 40 and over

      • Studies are all Scandinavian with well over 100,000 women with follow-up times of 10-29 years

      • All conclude that screening for breast cancer earlier results in earlier detection and reduced mortality

  • Statistics that Dr. Chetlen uses to talk with patients and colleagues:

    • In the US, 1 in 8 women will be diagnosed with breast cancer over their lifetime

    • Number of breast cancer cases in 2017 was 253,000 with an estimated 40,600 deaths

    • No decade of life (ie: 40’s, 50’s, 60’s) accounts for more than 25% of cancers diagnosed each year → there are no sudden jumps in incidence beyond the age of 50

    • Breast cancer incidence increases steadily with age

      • Age 40: 1 in 1000 will be diagnosed with breast cancer

      • Age 50: 2 in 1000 will be diagnosed with breast cancer

      • Age 60: 3 in 1000 will be diagnosed with breast cancer

    • The breast cancer found in women less than 40 are smaller in size, lower stage, less likely to receive chemotherapy

    • 75% of women diagnosed with breast cancer have no identifiable risk factors

  • Pearl: Facts and figures can be found on the Society of Breast Cancer Imaging’s website (https://www.sbi-online.org/endtheconfusion/Home.aspx)

  • Guidelines:

    • ACOG: annual mammograms starting at age 40

    • USPSTF, AAFP, ACP: biennial screening mammography for women 50-74. Decision to start before age 50 should be an individual one. Women who place higher value of potential benefit over the potential harms may choose biennial screening between ages 40-49.

    • American College of Radiology and Society of Breast Imaging: women at average risk should begin annual screening at age 40. Women of higher risk and African American women should begin risk assessment and screening at age 30.

    • American Cancer Society: annual screening mammography at age 45, biennial at age 55.

  • Benefits of early detection: Likely to exceed that of data from early randomized control trials because significant improvement since the 1970’s

    • Technology has improved

      • Early trials relied on single-view mammogram → standard today is two-views which increased detection by 20%

      • New improvements in mammo grids, newer target materials, automatic exposure control

      • Film screen to digital mammography

      • 2D to 3D mammography (tomosynthesis)

    • Longer term trials more recently found a greater mortality benefit than older, shorter term trials

  • Controversy around the USPSTF recommendations:

    • In 2009, they argued the benefit of screening before 40 did not outweigh the potential harms

    • Used data from randomized control trials to estimate a mortality reduction of only 15% in women aged 40-49 vs. 32% for women ages 60-69.

    • The data included a significantly flawed Canadian national breast cancer screening study trial that showed no benefit for women women 40-60.

      • Randomization occurred after a physical exam and palpation of the breasts, which meant blinding was not guaranteed

      • Women with palpable masses should not have been included in the screening trial because screening by definition means asymptomatic women (ie: no breast mass)

      • The physicist rated the mammography quality as far below state of the art at the time (ie: older equipment with out-of-date technology leading to poorer detection of cancer)

  • Concerns about overdiagnosis:

    • We can’t yet tell reliably which cancers will be aggressive and lead to death versus those cancers which are more benign

    • Women do experience short-term anxiety regarding breast cancer screening in general but it rapidly declines and has no measurable effect on their health

      • 96% of women who experienced a false positive screening mammogram support screening and would continue screening mammography

      • False positive actually increased their intention to undergo future breast cancer screening

  • A scenario of 1000 women receiving screening mammograms:

    • 100 are asked to come back for additional mammogram views, physical exam, ultrasound → 81 are called negative → 19 may undergo invasive needle biopsy → 5 diagnosed with breast cancer

    • Out of the 1000 women, 90% of those called back do NOT result in biopsy. Many centers offer same-day biopsy. Biopsy takes a few minutes with results returning in 2-3 days.

  • To the reader than says, “You’re talking to a radiologist - what about financial gain?”

    • 3D mammography is cost effective compared with 2D with recent study reporting overall savings of $28 per woman screened due to better images leading to less recall for further imaging and better less costly treatment (ie: early detection of breast cancer may mean no need for more expensive chemotherapy)

 

REFERENCES:

  1. American College of Obstetricians and Gynecologists. ACOG Statement on Breast Cancer Screening Guidelines. Published January 2016. https://www.acog.org/About-ACOG/News-Room/Statements/2016/ACOG-Statement-on-Breast-Cancer-Screening-Guidelines  

  2. American College of Radiology. ACR Appropriateness Criteria ®: Breast Cancer Screening. Revised 2017. https://acsearch.acr.org/docs/70910/Narrative/

  3. American College of Radiology/Society of Breast Imaging. USPSTF Breast Cancer Screening Recommendations Could Endanger Women. Published December 2016. https://www.sbi-online.org/Portals/0/Position%20Statements/2016/SBI%20ACR%20Response%20to%20USPSTF%20Recommendations.pdf

  4. American College of Radiology/Society of Breast Imaging. New ACR/SBI Breast Cancer Screening Guidelines Call for Significant Changes to Screening Process. Published April 2018. https://www.sbi-online.org/Portals/0/Position%20Statements/2018/New-2018-BCS-Guidelines.pdf

  5. Arleo EK, Henrick RE, Helvie MA, Sickles EA. Comparison of recommendations for screening mammography using CISNET models. Cancer 2017;123(19):3673-3680.

  6. Gabriel CA, Domchek SM. Breast cancer in young women. Breast Cancer Res. 2010;12(5):212. doi:10.1186/bcr2647

  7. Gotzche PC, Jorgensen K. Screening for breast cancer with mammography. Cochrane Database of Systematic Reviews 2013, Issue 6. DOI: 10.1002/14651858.CD001877.pub5

  8. Hellquist BN, Duffy SW, Abdsaleh S et al. Effectiveness of population‐based service screening with mammography for women ages 40 to 49 years. Cancer 2011;117:714-722. doi:10.1002/cncr.25650

  9. Hendrick RE, Helvie MA. United States Preventive Services Task Force Screening Mammography Recommendations: Science Ignored. American Journal of Roentgenology 2011;196(2):W112-116.

  10. Kalager M, Zelen M, Langmark F, et al. Effect of Screening Mammography on Breast Cancer Mortality in Norway. N Engl J Med 2010; 363:1203-1210.

  11. Lind E, Nakamura A, Thalabard JC. No overdiagnosis in the Norwegian Breast Cancer Screening Program estimated by combining record linkage and questionnaire information in the Norwegian Women and Cancer study. European Journal of Cancer 2018; 89:102-112. https://doi.org/10.1016/j.ejca.2017.11.003

  12. Miller AB, Wall C, Baines CJ, et al. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ 2014; 348 :g366

  13. Myers ER, Moorman P, Gierisch JM et al. Benefits and Harms of Breast Cancer Screening: A Systematic Review. JAMA 2015;314(15):1615-34. 

  14. National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Female Breast Cancer. https://seer.cancer.gov/statfacts/html/breast.html

  15. Oeffinger KC, Fontham ETH, Etzioni R, et al. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society. JAMA 2015;314(15):1599–1614. doi:10.1001/jama.2015.12783

  16. Partridge AH, Goldhirsch A, Gelber S, Gelber RD. Chapter 85: Breast Cancer in Younger Women, in Harris JR, Lippman ME, Morrow M, Osborne CK. Diseases of the Breast, 5th edition, Lippincott Williams & Wilkins, 2014.

  17. Pearlman MD. Breast cancer screening: is the controversy of benefits vs harms resolved? OBG Manag 2017;29(11):24-28. https://www.mdedge.com/obgmanagement/article/150334/breast-cancer/breast-cancer-screening-controversy-benefits-versus-harms

  18. Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst MA. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients BMJ 2015;351:h4901

  19. Tabár L, Vitak B, Hsiu-Hsi Chen T, et al. Swedish Two-County Trial: Impact of Mammographic Screening on Breast Cancer Mortality during 3 Decades. Radiology 2011; 260(3):658-663.

  20. Tosteson ANA, Fryback DG, Hammond CS, et al. Consequences of False-Positive Screening Mammograms. JAMA Intern Med 2014;174(6):954–961. doi:10.1001/jamainternmed.2014.981

  21. United States Preventive Services Task Force. Final Recommendation Statement: Breast Cancer: Screening. May 2019. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/breast-cancer-screening1

Wilt TJ, Harris RP, Qaseem A, for the High 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;162:718–725. doi: 10.7326/M14-2326

Ian L., Dr -

The American Cancer Society advocates for breast MRI in addition to mammography to be discussed in women with a 20% and more lifetime risk of breast cancer -Gail Model for Breast Cancer Risk on MD calc there are other models -eg Tyrer-Cuzik model
BRCA 1 BRCA2
First degree relative with BRCA gene
Life Assesment risk tools indicating 20% risk
Other Gene Syndromes .
Extremely Dense Breast Tissue
African -American People :30.3 % have elevated risk V's 13% for Caucasian United States Women
Other risks ?
It's cognitive and stress overload for sure .

Stephen P. -

Can you explain why there seems to be such a disparity between the 1 in 8 lifetime prevalence and the incidence per decade being only up to 2.1 per 1000?

Neda F., MD -

Hi Stephen. Here's Dr. Chetlen's response: "I would refer this listener to the Susan Koman website which explains how the 1 in 8 lifetime risk is calculated. https://ww5.komen.org/Breastcancer/Understandingrisk.html. The stats are derived from:

Howlader N, Noone AM, Krapcho M, et al. (editors). SEER*Explorer. Breast cancer-SEER incidence rates by age at diagnosis, 2012-2016, by sex. National Cancer Institute. Bethesda, MD. Accessed on May 7, 2019. https://seer.cancer.gov/explorer/, 2019."

Kapil S. -

Hi Neda, (conveniently) Dr. Chetlen didnt comment on the risks of overdiagnosis, ie: biopsy complications and unnecessary surgical intervention rates and complications. What are these rates/NNH in the 40-49 age category?

Kapil S. -

Being from Canada, I would direct everyone to read this debate between Family Physicians and a Radiologist written in the Collage of Family Physicians of Canada (CFPC)'s official journal "Canadian Family Physician":

1) Original article by Dickinson et al. " Quality of the screening process: An overlooked critical factor and an essential component of shared decision making about screening" https://www.cfp.ca/content/65/5/331#ref-24

2) Response by Dr. Paula Gordon (Radiologist) https://www.cfp.ca/content/65/7/457#ref-1

3) Response by Dickinson et al to Dr. Gordon : https://www.cfp.ca/content/65/11/769#ref-17

The debate continues..

Neda F., MD -

Thanks, Kapil. Here is Dr. Chetlen's response to your first question:

"Overdiagnosis is a hot topic and that’s a great question from the listener.
When a patient asks me about overdiagnosis, I state “Well, since we don’t know which DCIS will progress to invasive disease and affect your mortality, it is important to get you the information about the suspicious finding in your breast by doing a biopsy. Then you can make an informed decision about the management. Also remember that 5 mm of low grade DCIS is very different than 8 cm of high grade DCIS. There is the grade, extent and distribution, and location of the cancer that all come into play in decision making. And I hope that research continues to evolve and help us learn more about breast cancer. Until it does, I do recommend biopsy of that suspicious area in your breast so we can make informed decisions.”

Risks of overdiagnosis? Anecdotally (in my experience doing this 10 years), 95% of my patients DO want to have the information and do proceed with breast biopsy with no residual ill-effects. The risks are minimal (plenty of EBM to support this) and include potentially short term anxiety. Breast biopsy procedures are done with local anesthetic and take only a few minutes so we, of course, consent them for bleeding and infection risk but these risks are incredibly infrequent (also EBM to support this). Most of my patients leave the clinic with a bandaid and ice pack and say “Geez, that wasn’t as bad as I thought.” And they have the pathology results in 2 days.

Here is a snippet from a recent online discussion by Daniel Kopans, a respected breast imaging radiologist from Harvard (also a Fellow of the SBI) on Overdiagnosis. See below:
There are claims that screening leads to massive "overdiagnosis" of cancers that, if left undetected, would never become clinically evident and would fade away if left alone ([3]).
The exaggerated, mythological concept of "overdiagnosis" revolves around estimates of the Annual Percentage Change (APC) in the incidence of invasive breast cancers (there are legitimate questions about DCIS).
The fundamental question is, "had screening not begun in the mid 1980's would the incidence of invasive breast cancer been stable over the past decades or has it been increasing and if it has been increasing, how quickly has it increased?"
The APC is a measure of how much the incidence of breast cancer changes each year to reach the next year and the next year, etc. until you reach the year that ends the period you are studying. For example, if the incidence of invasive breast cancer was 60/100,000 in 1940 and it rose to 100/100,000 by 1980, then the amount it increased each year in between would be an APC = 1.3%. In other words, for the incidence to grow from 60/100,000 to 100/100,000 you would increase the incidence in 1940 by 1.3% and then you would increase the resulting incidence for 1941 by 1.3%, etc. so that by 1980 the incidence would have risen to 100 women/100,000 (the incidence in 1980). Had screening not begun in the mid 1980's, it is almost certain that the baseline incidence of breast cancer would have continued to increase at an APC of 1-1.3% into the screening era.
The "overdiagnosis" arguments are made up on the claim that had screening not begun at a National level in the mid 1980's, the incidence would have increased at an APC of 0.25% to at most an APC of 0.5% ([4]) or even stayed the same as it had been in the late 1970's (APC = 0.0%) ([5]). As a testament to poor peer review, those are the numbers used by one author publishing 3 separate articles in the New England Journal of Medicine in which he and his coauthors used all three "guesses" (his terminology) based on the same data! None of these three are supported by the facts.
Our National data come from the Surveillance Epidemiology and End Results (SEER) program of the NCI, but this program did not begin until 1974. The most credible data predating SEER come from the Connecticut Tumor Registry (CTR) used by most authors to examine breast cancer incidence prior to SEER ([6],[7],[8],[9]) and dating back to 1940. The CTR clearly shows that the incidence of breast cancer, prior to the start of any screening, had been increasing steadily with an APC of 1-1.3% per year since 1940.
In multiple other countries the incidence prior to the start of screening had been increasing even faster with an APC as high as 2% in the period before there was any screening for breast cancer. The suggestion of massive overdiagnosis relies on ignoring the actual data and, instead, using the lower "guesstimates" of the APC. Those seeking to reduce access to screening used the lower APC's of 0.0% - 0.5% to extrapolate what the baseline incidence would have been in 2008 and 2010 in the absence of screening. Since the actual incidence of breast cancer in 2008 and 2010 (SEER data) was considerably higher than an extrapolation using these low numbers, they argued that all the cancers above their claimed baseline incidence would have to be cancers that would have never become clinically evident and hence were "fake" and "overdiagnosed.”
Had these authors not "guessed", but had, instead acknowledged the actual increase in incidence over the decades preceding the start of screening showing an APC of 1.0-1.3% they would have found that had this continued into the screening era (and there is no reason to expect that it would not have continued), the actual incidence of breast cancer by 2008-2010 was not higher than the extrapolated baseline incidence. In fact it was actually lower . Not only were there no "fake cancers" "overdiagnosed", but there were actually fewer invasive cancers than would have been expected.
One might ask why there were actually fewer invasive cancers than an APC of 1.0%-1.3% would have predicted? It is likely that this is due to the removal of DCIS lesions over the preceding years that prevented them from progressing to invasive cancers (unproven, but likely).
All the available data suggest that the incidence of breast cancer had been steadily increasing for decades prior to the start of screening at an APC of 1% -1.3% . When your clinical colleagues challenge you and they claim that screening is leading to massive overdiagnosis you should explain that this false claim is based on, scientifically, false estimates of the APC. If the correct APC is used there is no "overdiagnosis" of invasive breast cancer, and, in fact, screening has likely resulted in fewer invasive cancers than would have been expected contributing to the decline in breast cancer deaths since 1990.
REFERENCES
[1] Kopans DB, Halpern E, Hulka CA. Statistical Power in Breast Cancer Screening Trials and Mortality Reduction Among Women 40-49 with Particular Emphasis on The National Breast Screening Study of Canada. Cancer 1994;74:1196-1203.
[2] Hendrick RE. Smith RA, Rutledge JH, Smart CR. Benefit of Screening Mammography in Women Ages 40-49: A New Meta-analysis of Randomized Controlled Trials. Monogr Natl Cancer Inst 1997;22:87-92.
[3] Gotzsche PC, Jorgensen KJ, Zahl PH, Mæhlen J. Why mammography screening hasn't lived up to expectations from the randomised trials. Cancer Causes Contr 2012;23:15-21.
[4] Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012 Nov 22;367(21):1998-2005
[5] Welch HG, Prorok PC, O'Malley AJ, Kramer BS. Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness. N Engl J Med. 2016 Oct 13;375(15):1438-1447.
[6] Shulman LN, Willett W, Sievers A, Knaul FM. Breast cancer in developing countries: opportunities for improved survival. J Oncol. 2010;2010
[7] Kessler LG, Feuer EJ, Brown ML. Projections of the breast cancer burden to U.S. women: 1990-2000. Prev Med. 1991 Jan;20(1):170-82
[8] Miller BA, Feuer EJ, Hankey BF. Recent incidence trends for breast cancer in women and the relevance of early detection: an update. CA Cancer J Clin. 1993 Jan-Feb;43(1):27-41
[9] Garfinkel L, Boring CC, Heath CW Jr. Changing trends. An overview of breast cancer incidence and mortality. Cancer. 1994 Jul 1;74(1Suppl):222-7"

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