Contralateral Prophylactic Mastectomy: Quantifying Benefits and Weighing the Harms

Abstract

Breast cancer is a disease that no woman wants to experience, let alone experience it more than once. For this and other reasons, some women choose to undergo prophylactic removal of the unaffected breast at their initial diagnosis of breast cancer. The path to this decision may be most clear for women who carry a mutation in the BRCA1 or BRCA2 gene, for whom the risk of a second primary cancer is high. However, for the vast majority of women with breast cancer, the risk of a contralateral breast cancer is lower. For these women at lower risk, how do they reconcile undergoing prophylactic mastectomy with the option of breast conservation, which has been shown to have an equivalent survival outcome compared with mastectomy? The decision is complex, and the benefits must be carefully evaluated against the risks and potential harms. Until recently, the extent of the benefit has not been quantified. The article by Herrinton et al in this issue not only quantifies the benefit for preventing a new breast cancer, but it also evaluates the impact on breast cancer mortality. However, careful interpretation of their results is needed to appropriately apply this information to help women make decisions regarding contralateral prophylactic mastectomy. The study by Herrinton et al, a large collaborative investigation by six health maintenance organizations, demonstrates the strength that can be gained by large collaborative networks, as well as the challenges in harvesting valuable clinical data from medical practices. The study examined 56,400 women with breast cancer diagnosed between 1979 and 1999, of whom 1.9% underwent a contralateral prophylactic mastectomy. Despite the availability of computerized records, culling the data was a daunting challenge. More than 2,200 records of women were reviewed, and less than half of the women (n 1,072) were ultimately proven to have had a contralateral prophylactic mastectomy. Why was there difficulty in identifying these women? One problem is that there is no specific code to identify this procedure. Studying the impact of the procedure on health outcomes can be greatly facilitated by developing unique procedure codes. Another complexity in the design and interpretation of the study is the sampling scheme used to assess the impact of prophylactic mastectomy on breast cancer occurrence, taking into account all other individual patient characteristics. Despite a large proportion of computerized records, detailed chart abstraction was required and could only be performed for a subset of the women in the study. The occurrence of contralateral breast cancer is a rare event, with an estimated rate of 2.7%. These women were oversampled to have adequate numbers to compare with women who underwent prophylactic mastectomy, while also adjusting for potential confounders. Although it permits valid estimation of outcome, unfortunately, this sampling scheme does not allow direct statistical comparison of differences in characteristics between the two groups. Further examination of the underlying differences in the women who chose to either have or not have prophylactic contralateral mastectomy would be valuable. With the increasing availability of electronic records, this type of research will be facilitated without the need for such complex sampling schemes. The observed impact of contralateral mastectomy on the occurrence of breast cancer was, as one would expect, profound. The risk was reduced by 97%, adjusting for primary and adjuvant therapy, characteristics of the tumor, and family history. Five women (0.5%) in the contralateral prophylactic mastectomy group developed a contralateral breast cancer despite this procedure. From these data, women may be counseled that their risk will be dramatically reduced but not completely eliminated. Additional information on other factors associated with a contralateral breast cancer is also provided. Interestingly, chemotherapy, JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 19 JULY 1 2005