Re: Influence of breast density on breast cancer diagnosis

The authors are to be applauded for performing this study [BCMJ 2019;61:376-384]. They have listed some of the limitations in their methodology (Study challenges), but there are others pertinent to their conclusions.

Objective 2 was to assess the stability of BI-RADS density categories assigned to screening participants. They used a subset of the mammograms of participants age 40 to 74 obtained in 2017 using digital mammography and compared them with earlier mammograms. Density may diminish during the menopause transition.[1] They apparently did not ensure that the two examinations were either both done premenopausally or postmenopausally. This could introduce further discordance and exaggerate the calculated instability of the density assessment. Similarly, hormone therapy can increase density.[2,3] They apparently did not make efforts to avoid comparing examinations while on, and subsequent to, discontinuing hormone therapy, so additional discordance could result. The information on hormone use is collected at the time of the screening appointment, but the authors did not take this into account.

Objective 3 was to examine the influence of density on the risk of breast cancer. They included mammograms performed from 2011 to 2015, but they excluded screening rounds that followed an abnormal result. It has been shown that women with a history of a false-positive mammogram result may be at increased risk of developing breast cancer for up to 10 years after the false-positive result.[4-8] By excluding screening rounds that followed an abnormal result from the analysis, they may have underestimated the influence on breast cancer risk.

They aimed to estimate rates for screen-detected and interval cancer for participants at average risk and higher-than-average risk. But the BC Cancer Breast Screening Program (BCCBSP) limits “increased risk” only to women with a first degree family history of breast cancer.[9] It is known that women who use hormone therapy are at increased risk,[3] as are women with dense breasts.[10-12] By not acknowledging these additional risks, and including them with average risk women, the authors may have underestimated the true difference in risk between average- and higher-than-average-risk women. This may explain why there wasn’t a greater difference in the interval cancer rates and why they did not show greater nodal involvement in the interval cancers.

So it may not be true that, as the authors state, “Following a normal screening mammogram, a screening participant’s risk of being diagnosed with an interval breast cancer over the next screening round . . . is roughly similar at 1 year for women at elevated risk to that at 2 years for women at non-elevated risk.”

Even with these limitations, they still showed that tumors in screen-detected cancers were smaller than in interval cancers and less likely to have nodal involvement, and that within the screen-detected cancers, tumor size increased with increasing density.

The authors state that, “Current Canadian breast screening recommendations do not indicate further breast screening in addition to routine mammography,” but these are based on the 2018 guidelines from the Canadian Task Force on Preventive Health Care.[13] This is a committee that excludes experts funded by the federal Minister of Health through the Public Health Agency of Canada. When challenged in question period by the NDP health critic, both the Minister of Health and her parliamentary secretary insisted that, “These are not government guidelines.” And indeed, BCCBSP does not follow them to the letter.[14]

In discussions with patients, family physicians should be aware that the Task Force limited their review to randomized controlled trials performed from the 1960s to the early 1990s that studied only mortality reduction as a benefit to screening. They ignored metrics on reduced morbidity, which are of considerable importance to women—fewer mastectomies, fewer axillary dissections and resulting lymphedema, and less need for chemotherapy when cancers are detected early during screening.[15-18]

This is also the case with the US Preventive Services Task Force, which considers evidence to be insufficient to recommend any adjunctive screening on the basis of breast density alone,[19] and yet 39 states now inform women of their breast density and the FDA has introduced legislation that, when passed, will require all women to be informed.[20] And many states offer supplemental screening covered by health insurance. In Connecticut, where legislation was passed in 2009, practices have been detecting three to four additional cancers missed on mammograms per thousand average-risk women with BI-RADS C and D densities.[21] This constitutes a doubling of the cancer detection rate in dense breasts; cancers that would have presented later as interval cancers with worse prognostic characteristics if undetected. Austria, France, and one state in Australia include supplemental screening ultrasound for women with dense breasts in their screening programs. Reduction of interval cancers as seen in the Japan Strategic Anti-cancer Randomized Trial (J-START),[22] is a prerequisite of reduced mortality. So to insist on waiting for results of this trial, and say that there is no evidence to support supplemental screening, is misleading.

Yes, there are false positives associated with initiation of screening ultrasound, but these diminish with subsequent screening rounds. And the associated biopsies may cause inconvenience, but they are performed as percutaneous needle biopsies with local anesthetic, are well tolerated, and are similar (or less) for most women to the discomfort of a venipuncture: a small price to pay for the opportunity of early detection. The decision to have supplemental screening, which is now an insured service in British Columbia, should be made with shared decision making between a women and her physician, with all the information above.
—Paula B. Gordon, OBC, MD, FRCPC, FSBI
Vancouver

This letter was submitted in response to “The influence of breast density on breast cancer diagnosis: A study of participants in the BC Cancer Breast Screening Program.”

References

1.    Boyd N, Martin L, Stone J, et al. A longitudinal study of the effects of menopause on mammographic features. Cancer Epidemiol Biomarkers Prev 2002;11:1048-1053.

2.    Azam S, Lange T, Huynh S, et al. Hormone replacement therapy, mammographic density, and breast cancer risk: A cohort study. Cancer Causes Control 2018;29:495-505.

3.    Kerlikowske K, Cook AJ, Buist DS, et al. Breast cancer risk by breast density, menopause, and postmenopausal hormone therapy use. J Clin Oncol 2010;28:3830-3837.

4.    Henderson LM, Hubbard RA, Sprague BL, et al. Increased risk of developing breast cancer after a false-positive screening mammogram. Cancer Epidemiol Biomarkers Prev 2015;24:1882-1889.

5.    McCann J, Stockton D, Godward S. Impact of false-positive mammography on subsequent screening attendance and risk of cancer. Breast Cancer Res 2002;4:R11.

6.    Barlow WE, White E, Ballard-Barbash R, et al. Prospective breast cancer risk prediction model for women undergoing screening mammography. J Natl Cancer Inst 2006;98:1204-1214.

7.    Von Euler-Chelpin M, Risor LM, Thorsted BL, Vejborg I. Risk of breast cancer after false-positive test results in screening mammography. J Natl Cancer Inst 2012;104:682-689.

8.    Castells X, Roman M, Romero A, et al. Breast cancer detection risk in screening mammography after a false-positive result. Cancer Epidemiol 2013;37:85-90.

9.    Wilson CM. Screening Mammography Program, BC Cancer Agency. Updated breast screening policy for higher than average risk women. 19 March 2015. Accessed 13 December 2019. www.bccancer.bc.ca/family-oncology-network-site/Documents/SMPPresentationIncludingDigital_V06_FINAL.pdf.

10.    Harvey JA, Bovbjerg VE. Quantitative assessment of mammographic breast density: Relationship with breast cancer risk. Radiology 2004;230:29-41.

11.    Engmann NJ, Golmakani MK, Miglioretti DL, et al. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol 2017;3:1228-1236.

12.    McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: A meta-analysis. Cancer Epidemiol Biomarkers Prev 2006;15:1159-1169.

13.    Klarenbach S, Sims-Jones N, Lewin G, et al. Recommendations on screening for breast cancer in women aged 40–74 years who are not at increased risk for breast cancer. CMAJ 2018;190:E1441-E1451.

14.    YouTube. Don questions the health minister on the government’s new breast cancer screening guidelines. Accessed 13 December 2019. www.youtube.com/watch?time_continue=4&v=62yyMjgVclQ&feature=emb_logo.

15.    Ahn S, Wooster M, Valente C, et al. Impact of screening mammography on treatment in women diagnosed with breast cancer. Ann Surg Oncol 2018;25:2979-2986.

16.    Coldman AJ, Phillips N, Speers C. A retrospective study of the effect of participation in screening mammography on the use of chemotherapy and breast conserving surgery. Int J Cancer 2007;120:2185-2190.

17.    Shah C, Vicini FA. Breast cancer-related arm lymphedema: Incidence rates, diagnostic techniques, optimal management and risk reduction strategies. Int J Radiat Oncol Biol Phys 2011;81:907-914.

18.    Yaffe MJ, Jong RA, Pritchard KI. Breast cancer screening: Beyond mortality. J Breast Imaging 2019;1:161-165.

19.    Siu AL, U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2016;164:279-296.

20.    US Food and Drug Administration. FDA advances landmark policy changes to modernize mammography services and improve their quality. 27 March 2019. Accessed 13 December 2019. www.fda.gov/news-events/press-announcements/fda-advances-landmark-policy-changes-modernize-mammography-services-and-improve-their-quality.

21.    Weigert JM. The Connecticut Experiment; The third installment: 4 years of screening women with dense breasts with bilateral ultrasound. Breast J 2017;23:34-39.

22.    Ohuchi N, Suzuki A, Sobue T, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): A randomised controlled trial. Lancet 2016;387(10016):341-348.