Radiation therapy and the risk of contralateral breast cancer

The article by Gao, Fisher, and Emami in this issue of the International Journal of Radiation Oncology Biology Physics (1) adds to a growing body of literature evaluating the risks of contralateral breast cancer in women treated for early-stage breast cancer. The authors obtained data from the SEER database to study the incidence of contralateral breast cancer after treatment for unilateral localized breast cancer. Overall, the use of radiotherapy did not contribute to the risk of a contralateral breast cancer (RR: 1.04, 95% confidence range: 0.97–1.10). However, when evaluated as a function of follow-up period, radiotherapy seems to increase the risk slightly (RR: 1.14, 95% confidence range: 1.03–1.26) for patients followed more than 5 years. The take-home message of this study is that although radiotherapy seems to be associated with an incrementally increased long-term risk of contralateral breast cancer, the risk is exceedingly small and should not affect the clinical decision making in treatment selection for patients with early-stage breast cancer considering radiation as a component of localregional management. This important point should be reassuring to clinicians and patients faced with different management options. The authors appropriately indicate that measures to minimize exposure to the contralateral breast are desirable. Other findings of note in this study include the observation of higher rates of contralateral breast cancer associated with medullary histology, African-American race, and age over 55. Increasing risk with age is not surprising, given the known association of advancing age with the development of breast cancer. The observation of a higher rate of contralateral breast cancers among patients with medullary histology may be explained by the known association of medullary carcinomas with hereditary BRCA1 and BRCA2 associated cancers. Although not all patients with medullary histology have germline mutations in BRCA1 or BRCA2, patients with medullary histology have been shown to be more likely to have a genetic predisposition to the disease and are therefore more likely to develop contralateral disease (2, 3). Unfortunately, this information was not available from the SEER database to confirm this speculation. The observation that African-American race is associated with a higher rate of contralateral breast cancer warrants further study. Although the patient numbers are small and the relative risk was only slightly elevated (RR: 1.2, 95% confidence limits range: 1.08–1.33), the increased risk was significant at p 0.0009 in multivariate analysis. Of note, the use of radiation therapy did not seem to have any significant influence on the development of contralateral breast cancer in the African-American population. Clearly, additional investigations are needed to further evaluate the observation of higher contralateral breast cancer risks among African-American women treated for breast cancer. There are several cautionary points from this study that should be noted. First, these data are from a large centralized data bank, with some uncertainties regarding the accuracy of all data. As the authors point out, information regarding family history, hormonal therapy, and chemotherapy in the initial management was not available. Furthermore, the data regarding the use of radiotherapy may not be totally accurate. According to the data presented, less than one-third of the patients in the database actually received radiation therapy. Although many of these patients may have been treated by mastectomy, the use of radiotherapy in this group of patients with localized disease, in my view, seems to be low. It should be noted that SEER obtains these data from hospital tumor registries, which code for the use of radiotherapy within a specific window from the initial diagnosis (during the time of this data acquisition, the window was approximately 4 months). Although the registries do an excellent job of attempting to track and correctly code this information, the data abstractors rely on information provided by others, and inaccuracies are inevitable. If radiotherapy was delayed, or if the registries had no record of radiotherapy or failed to capture the use of radiotherapy for any reason, its use would be underreported. It is, of