{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:42:49Z","timestamp":1790764969333,"version":"4.1.0"},"reference-count":46,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"Importance<\/jats:title>Breast cancer is the most common invasive subsequent malignant disease in childhood cancer survivors, though limited data exist on changes in breast cancer rates as primary cancer treatments have evolved.<\/jats:p><\/jats:sec>Objective<\/jats:title>To quantify the association between temporal changes in cancer treatment over 3 decades and subsequent breast cancer risk.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>Retrospective cohort study of 5-year cancer survivors diagnosed when younger than 21 years between 1970 and 1999, with follow-up through December 5, 2020.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Radiation and chemotherapy dose changes over time.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Breast cancer cumulative incidence rates and age-specific standardized incidence ratios (SIRs) compared across treatment decades (1970-1999). Piecewise exponential models estimated invasive breast cancer and ductal carcinoma in situ (DCIS) risk and associations with treatment exposures, adjusted for age at childhood cancer diagnosis and attained age.<\/jats:p><\/jats:sec>Results<\/jats:title>Among 11\u202f550 female survivors (median age, 34.2 years; range 5.6-66.8 years), 489 developed 583 breast cancers: 427 invasive, 156 DCIS. Cumulative incidence was 8.1% (95% CI, 7.3%-9.0%) by age 45 years. An increased breast cancer risk (SIR, 6.6; 95% CI, 6.1-7.2) was observed for survivors compared with the age-sex-calendar-year-matched general population. Changes in therapy by decade included reduced rates of chest (34% in the 1970s, 22% in the 1980s, and 17% in the 1990s) and pelvic radiotherapy (26%, 17%, and 13% respectively) and increased rates of anthracycline chemotherapy exposures (30%, 51%, and 64%, respectively). Adjusting for age and age at diagnosis, the invasive breast cancer rate decreased 18% every 5 years of primary cancer diagnosis era (rate ratio [RR], 0.82; 95% CI, 0.74-0.90). When accounting for chest radiotherapy exposure, the decline attenuated to an 11% decrease every 5 years (RR, 0.89; 95% CI, 0.81-0.99). When additionally adjusted for anthracycline dose and pelvic radiotherapy, the decline every 5 years increased to 14% (RR, 0.86; 95% CI, 0.77-0.96). Although SIRs of DCIS generally increased over time, there were no statistically significant changes in incidence.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Invasive breast cancer rates in childhood cancer survivors have declined with time, especially in those younger than 40 years. 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