Long-term risk of second malignancies in women after breast conservation therapy for ductal carcinoma in situ or early-stage breast cancer.

PURPOSE: Women with ductal carcinoma in situ (DCIS) or early-stage breast cancer have an excellent prognosis, but their risk of developing second malignant neoplasms (SMNs) is not well established. We analyzed SMNs in a large cohort with long follow-up after breast conservation therapy.

METHODS: The study population comprised 755 women with DCIS (n = 135) or stage I-II breast carcinoma (n = 620). Subjects were aged 25-89 (median 55) years when they underwent breast-conserving surgery followed by radiotherapy to the entire breast (60-68Gray) between 1992 and 2001. Additional treatment included hormonal therapy and/or chemotherapy based on clinical characteristics. SMNs were grouped by site. The rate of SMNs over time was determined using the Kaplan-Meier method. To compare the probability of developing SMNs overall and for specific organs or sites, probability estimates were obtained for a 55-year-old female from the Surveillance, Epidemiology, and End Results Program (SEER).

RESULTS: Median follow-up from radiotherapy was 13.8 years. The 15-year age-adjusted probability of developing any SMN was 12.0%, close to the SEER rate of 12.1% for a non-breast malignancy. Systemic therapy and higher-dose radiotherapy (> 63 Gray) were not associated with significantly increased risks of SMNs. Compared to SEER, significantly increased risk was noted for gynecologic cancers and melanoma.

CONCLUSIONS: Most SMNs were unrelated to treatment, and the 15-year incidence was similar to that of cancer in the SEER control group-findings that should be reassuring to patients. Further risk reduction is expected from prophylactic gynecologic surgery. Continued investigations into genetic links with melanoma are warranted.