Editorial: Refining Risk Assessment in Women With Benign Breast Disease: An Ongoing Dilemma

JNCI: Journal of the National Cancer Institute, Oct 2017

Schnitt, Stuart J, Morrow, Monica, Tung, Nadine M

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Editorial: Refining Risk Assessment in Women With Benign Breast Disease: An Ongoing Dilemma

JNCI J Natl Cancer Inst ( Refining Risk Assessment in Women With Benign Breast Disease: An Ongoing Dilemma Stuart J. Schnitt 0 1 Monica Morrow 0 1 Nadine M. Tung 0 1 0 The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions , please 1 Affiliations of authors: Department of Pathology (SJS) and Division of Hematology-Oncology (NMT), Beth Israel Deaconess Medical Center and Harvard Medical School , Boston , MA; Department of Surgery, Memorial Sloan Kettering Cancer Center , New York, NY, MM , USA - More than three decades ago, Dupont and Page published their seminal study relating breast cancer risk to the histologic findings in benign breast biopsies ( 1 ). The key observations of that study were that women whose biopsy showed proliferative lesions without atypia had about a twofold increase in the risk of subsequent breast cancer and those with atypical hyperplasia had about a fivefold increase in breast cancer risk when compared with women with nonproliferative lesions. As summarized in Table 1, subsequent studies from other groups have yielded strikingly similar findings, despite differences in the study design, patient populations, and pathologists involved in the histologic classification of the benign breast biopsies ( 1–5 ). As a result of these studies, which in aggregate have included more than 17 000 women, atypical hyperplasia is considered a high-risk lesion and is included in risk assessment models such as the Gail/Breast Cancer Risk Assessment Tool (BCRAT) ( 6,7 ) and the International Breast Cancer Intervention Study (IBIS) model (8); proliferative lesions without atypia are also included in the IBIS model. Further, the finding of proliferative lesions in a benign breast biopsy, especially atypical hyperplasia, can result in more intensive screening and pharmacologic risk reduction with selective estrogen receptor modulators or aromatase inhibitors ( 9 ). In this issue of the Journal, Visscher et al. report on the risk of breast cancer among a small subset of women in the Mayo Clinic Benign Breast Disease (BBD) cohort who had multiple metachronous benign breast biopsies ( 10 ). Among 1414 women who had more than one biopsy (10.5% of their study population), there was a change in BBD category between the first and subsequent biopsy in 43.9% of cases. Further, the authors observed that a change from a lower-risk to a higher-risk BBD category between the first and subsequent biopsy was associated with an increase in breast cancer risk whereas a change from a higher-risk to a lower-risk BBD category was associated with a reduction in risk. What are the implications of these findings for clinical management, and what insights do they provide regarding the biology of breast tumor progression? In our view, the clinical management issues are straightforward for women whose second biopsy shows a higher-risk category of BBD than the initial biopsy, particularly for those women whose subsequent biopsy shows atypical hyperplasia. According to the data of Visscher et al., these women are at least the same level of increased risk as any other women with atypical hyperplasia (if not higher) and they should be managed accordingly ( 10 ). The most interesting group is the subset of women who had atypical hyperplasia in the first biopsy but had nonproliferative lesions or proliferative lesions without atypia in the subsequent biopsy. The data of Visscher et al. suggest that these women have a 43% reduction in breast cancer risk when compared with women who still have atypical hyperplasia in their second biopsy ( 10 ). However, this scenario appears to be extremely uncommon; 42 such women were identified in this study, representing only 3% of women with multiple biopsies and 0.3% of the entire Mayo Clinic BBD Cohort ( 10 ). Further, before concluding that these patients are no longer at high risk of breast cancer, it should be noted that this reduction in risk was not statistically significant. In addition, these women continue to have over a threefold increase in their risk of breast cancer (hazard ratio ¼ 3.36, 95% confidence interval ¼ 1.34 to 8.45) when compared with women who had nonproliferative lesions in both their first and subsequent biopsies. Finally, given the persistently elevated breast cancer risk in this group, it is possible that atypical hyperplasia is in fact present in the breast tissue, but in areas other than that subjected to the subsequent biopsy. We view this as plausible because more than half of the subsequent biopsies in this population were performed for clinically detectable lumps or mammographic masses (Supplementary *CI ¼ confidence interval; RR ¼ relative risk. Nonproliferative disease RR (95% CI) Proliferative disease without atypia RR (95% CI) 1 (ref) 1 (ref) Table 3, available online) ( 10 ); the finding of atypical hyperplasia in such specimens is much less common than in biopsies performed because of mammographic (...truncated)


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Schnitt, Stuart J, Morrow, Monica, Tung, Nadine M. Editorial: Refining Risk Assessment in Women With Benign Breast Disease: An Ongoing Dilemma, JNCI: Journal of the National Cancer Institute, 2017, Volume 109, Issue 10, DOI: 10.1093/jnci/djx036