Tools for Contralateral Prophylactic Mastectomy Decision Making

Mitchell H. Gail, MD, PhD; Ismail Jatoi, MD, PhD

Disclosures

J Clin Oncol. 2022;40(31):3653-3659. 

In This Article

Abstract and Introduction

Abstract

Purpose: Women with unilateral breast cancer are increasingly opting for the removal of not only the involved breast, but also for the removal of the opposite uninvolved breast (contralateral prophylactic mastectomy [CPM]), although the risk of contralateral breast cancer (CBC) has decreased in recent years. Models to predict the absolute risk of CBC can help a woman decide whether to undergo CPM. Our objective is to illustrate that a better decision can be made if the patient and doctor also have estimates of the absolute risks of regional and distant recurrences and mortality from non–breast cancer causes.

Materials and Methods: We based our analyses on two published models for CBC and published information on the hazards of regional and distant recurrences and non–breast cancer mortality. Assuming that CPM eliminates CBC but has no effect on other events, we calculated how much CPM reduces a woman's CBC risk and total risk from all these events for 10 hypothetical women with various subtypes of breast cancer and risk factors.

Results: The risk of CBC and total risk vary greatly, depending on the breast cancer subtype. In some cases, a decision for or against CPM can be based on CBC risk alone, but in others, additional consideration of total risk may cause a woman to decline CPM.

Conclusion: There is a potential to develop more informative tools for deciding on CPM. Realizing this potential will require more and better data to validate existing models of absolute CBC risk and to characterize the hazards of regional and distant recurrences and deaths from non–breast cancer causes for women with various subtypes of breast cancers and risk factors.

Introduction

Women with unilateral breast cancer are often concerned about developing cancer in the opposite unaffected breast (contralateral breast cancer [CBC]).[1] Greater numbers of these women are now opting not only for surgical removal of the involved breast, but also for simultaneous removal of the contralateral uninvolved breast, namely contralateral prophylactic mastectomy (CPM). Worldwide, rates of CPM have increased substantially since the late 1990s, with a nearly 6-fold increase reported in the United States between 1998 and 2011.[2] Currently, many women in the United States who are diagnosed with unilateral invasive breast cancer or ductal carcinoma in situ (DCIS) inquire about CPM, and rates of CPM for invasive cancer have been reported to be as high as 42% for women between the ages of 20–44 years in some states within the United States.[3] Two recent models estimate the individualized absolute risk of invasive or in situ CBC for carriers of BRCA1 or BRCA2 mutations[4] and for the general population.[4,5] Although absolute CBC risk is an essential ingredient in making an informed decision, the woman should also know the other risks she is facing, such as regional and distant cancer recurrence and death from non–breast cancer causes, to put the CBC risk into perspective.

In data from the Netherlands from 1999 to 2017, the average 10-year risk of CBC was estimated to be about 3.5% for women with invasive cancer and about 4.5% for those with DCIS.[6,7] Lower 10-year CBC risks of 2.6% were reported for women with invasive breast cancer in the United States.[8] However, risk estimates vary widely, and are substantially higher for carriers of high-risk pathogenic germline mutations (ie, involving the BRCA1, BRCA2, PTEN, STK11, CDH1, P53, or PALB2 genes) or for patients who received radiotherapy to the anterior chest wall for childhood malignancies such as Hodgkin lymphoma, with the 25-year risk approaching 50% in these women.[9] The risk of CBC is higher for patients with estrogen receptor/progesterone receptor (ER/PR)–negative tumors and those with lobular histology,[10] and adjuvant systemic therapies lower CBC risk.[6,11–13] Ironically, CPM rates have increased during a time period when CBC incidence decreased substantially, because of the availability of more effective adjuvant systemic therapies.[12]

The decision to undergo CPM should be based on comparing its benefits and risks. The immediate costs of CPM include doubling the risks of wound infections, bleeding, hematomas, and edema, and occasional need for further operations to treat surgical complications arising from CPM.[1] Other potential adverse effects include sense of loss, unfavorable perceptions of body image and femininity, and abnormal chest wall sensations, although most women who choose CPM are satisfied with their decision.[1] The benefits of CPM include removing or reducing risk of CBC and relief of anxiety about CBC and about cancer more generally.[1] The evidence from observational studies is mixed concerning the extent to which CPM reduces breast cancer–specific mortality, and there is little evidence it reduces overall mortality.[1] This study discusses the extent to which CPM reduces a woman's CBC risk and puts that reduction in the context of her total risk that also includes regional and distant metastases and death from non–breast cancer causes.

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