Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: A population-based study

Abstract

Purpose To study the potential risk factors, including radiotherapy (RT) for contralateral breast cancer (CBC), in patients treated for early-stage breast cancer. Methods and materials The Surveillance, Epidemiology, and End Results database (1973–1996) was used to study the incidence of CBC after breast cancer. The Cox proportional hazards regression model was used to estimate the relative risk (RR) of CBC, with adjustment for confounders, including age, race, histologic subtype, and use of RT. Information on the use of hormonal therapy and chemotherapy was not available in the Surveillance, Epidemiology, and End Results database. Results A CBC was documented in 5679 (4.2%) of the 134,501 localized invasive or intraductal breast cancer patients surviving at least 3 months. The 10- and 20-year actuarial rate of CBC was 6.1% and 12%, respectively. In multivariate analysis, medullary carcinoma (RR = 1.18, 95% confidence interval [CI] 1.02–1.37), black race (RR = 1.20, 95% CI 1.08–1.33), and age >55 years at initial diagnosis (RR = 1.15, 95% CI 1.08–1.22) were associated with increased CBC risk. A total of 1234 (3.3%) of 37,379 patients who received RT developed CBC, and 4445 (4.6%) of 97,122 patients who did not receive RT developed CBC. Overall, RT was not associated with an increased risk of CBC (RR = 1.04, 95% CI 0.97–1.10) in multivariate analysis. The CBC risk associated with RT varied substantially with the length of follow-up. During the first 5 years of follow-up, RT was not associated with an increased CBC risk (age-adjusted RR = 0.96, 95% CI 0.88–1.04). For patients surviving for >5 years, RT was associated with a 14% increase in CBC risk (RR = 1.14, 95% CI 1.03–1.26). The increased CBC risk with RT was evident in patients aged <45 years (RR = 1.32, p = 0.01) and >55 years (RR = 1.15, p = 0.04) at initial diagnosis. The 5-, 10-, 15-, and 20-year actuarial rate of CBC was 2.9%, 6.5%, 10.2%, and 13.4%, respectively, for patients with RT; the corresponding rates were 3.0%, 6.0%, 8.9%, and 11.8% for patients without RT. The absolute increase in CBC risk associated with RT was 0.5%, 1.3%, and 1.6% in the 10-, 15-, and 20-year actuarial rate, respectively. Conclusion CBC is not uncommon after breast cancer, especially for certain subsets of patients. RT was associated with a very small increased long-term CBC risk. This minimal increase in CBC risk should not affect clinical decision-making in treatment selection for patients with localized invasive breast cancer or ductal carcinoma in situ. Unnecessary radiation exposure to the contralateral breast should be avoided for all patients with early-stage breast cancer.