Breast cancer recurrence and mortality among survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

10066 Background: Survivors of childhood cancer are at high risk for developing subsequent breast cancer (BC). However, BC recurrence risk and survival after BC recurrence has not been evaluated in survivors of childhood cancer. Methods: Analyses included female 5-year survivors participating in CCSS with pathology-ascertained breast carcinomas (in situ or invasive) diagnosed from 1981-2016 at age ≥18y. BC treatment was evaluated against chronological period-specific National Comprehensive Cancer Network guidelines for primary BC. Recurrent BC cumulative incidence was estimated treating death as a competing risk among survivors and females with first primary BC (controls) matched one-to-one by demographics and first BC clinical characteristics including diagnosis age/year, histology and race/ethnicity (206 pairs with complete data). Among survivors and controls with recurrent BC, all-cause mortality was evaluated with cumulative incidence with time at risk starting at relapse and hazard ratios from multivariable Cox regression models adjusted for age and calendar year of recurrence and race/ethnicity. Results: Among the 431 childhood cancer survivors with subsequent BC (median diagnosis age: 40 years, IQR: 35-44), 68 developed recurrent BC. Compared with matched controls, survivors had similar 10-year BC recurrence risk (survivors: 14%, 95% CI: 9-20% versus controls: 12%, 95% CI: 9-18%; P=0.52). Among survivors with BC recurrence, Hodgkin lymphoma was the predominant primary cancer diagnosis (63%) and first subsequent BCs were largely early stage (stage 0: 8%; stage I/II: 69%) and estrogen (71%) or progesterone (80%) receptor positive. Most (84%) received first BC treatment following national guidelines for primary BC. However, nearly half (47%) underwent bilateral mastectomies (81% occurring before recurrence) and most received chest radiotherapy (86%) or anthracycline chemotherapy (69%) for either their primary childhood cancer or first subsequent BC. A total of 48 survivors died after BC recurrence, mostly related to BC (83%) or cardiovascular causes (11%). Following recurrence, the 10-year overall mortality probability was significantly higher among survivors (89%, 95% CI: 61-97%) than controls (42%, 95% CI: 18-58%; P=0.0025) and survivors had an adjusted 2.6-fold (95% CI: 1.05-6.49) greater risk of death. Conclusions: Although the risk for BC recurrence among childhood cancer survivors with subsequent BC is similar to females with primary BC, this vulnerable population faces substantially greater mortality risk after recurrence. Future studies to identify early predictors of subsequent BC and BC recurrence among survivors are needed to reduce mortality risk.