Mortality After Breast Cancer Among Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Abstract

PURPOSE Female survivors of childhood cancer have a high risk of subsequent breast cancer. We describe the ensuing risk for mortality and additional breast cancers. PATIENTS AND METHODS Female participants in the Childhood Cancer Survivor Study, a cohort of 5-year survivors of cancer diagnosed between 1970 and 1986 before age 21 years, and subsequently diagnosed with breast cancer (n = 274; median age at breast cancer diagnosis, 38 years; range, 20 to 58 years) were matched to a control group (n = 1,095) with de novo breast cancer. Hazard ratios (HRs) and 95% CIs were estimated from cause-specific proportional hazards models. RESULTS Ninety-two childhood cancer survivors died, 49 as a result of breast cancer. Overall survival after breast cancer was 73% by 10 years. Subsequent risk of death as a result of any cause was higher among childhood cancer survivors than among controls (HR, 2.2; 95% CI, 1.7 to 3.0) and remained elevated after adjusting for breast cancer treatment (HR, 2.4; 95% CI, 1.7 to 3.2). Although breast cancer–specific mortality was modestly elevated among childhood cancer survivors (HR, 1.3; 95% CI, 0.9 to 2.0), survivors were five times more likely to die as a result of other health-related causes, including other subsequent malignant neoplasms and cardiovascular or pulmonary disease (HR, 5.5; 95% CI, 3.4 to 9.0). The cumulative incidence of a second asynchronous breast cancer also was elevated significantly compared with controls ( P < .001). CONCLUSION Mortality after breast cancer was higher in childhood cancer survivors than in women with de novo breast cancer. This increased mortality reflects the burden of comorbidity and highlights the need for risk-reducing interventions.

Inflammation Mediates the Development of Aggressive Breast Cancer Following Radiotherapy

“…RP-BC is reported to be more aggressive in several studies (3)(4)(5), but not all (7). Importantly, cancer survivors also have a poor prognosis because of other health-related causes, including other subsequent malignant neoplasms and cardiovascular or pulmonary disease (7). Considerable clinical evidence now associates TIL with cancer prognosis (22,50); thus, the absence of TIL in RP-BC is consistent with the previous clinical observations.…”

“…Our studies extend the finding by Horst et al that the spectrum of cancers in RP-BC is distinct from that of age-matched sporadic-BC. RP-BC is reported to be more aggressive in several studies (3)(4)(5), but not all (7). Importantly, cancer survivors also have a poor prognosis because of other health-related causes, including other subsequent malignant neoplasms and cardiovascular or pulmonary disease (7).…”

“…Horst and colleagues reported that compared with age-matched, sporadic-BC, women treated with radiation for Hodgkin's lymphoma (HL) are significantly more likely to be diagnosed with triple-negative breast cancer (TNBC) lacking hormone receptors and human epidermal growth factor receptor 2 (HER2), which has a poorer prognosis compared to more prevalent hormone receptor positive cancer (5). Childhood cancer survivors indicate that these patients have worse outcomes, regardless of breast cancer type (6,7).…”

Reflecting on 20 years of breast cancer modeling in CISNET: Recommendations for future cancer systems modeling efforts

“…These women also face higher competing mortality due to treatment-related late effects and a high burden of chronic diseases at an early age. [ 53 ] This competing mortality may reduce benefits from screening and treatment. Although the Children’s Oncology Group recommends early screening for breast cancer with mammography and breast MRI for these survivors starting at age 25 [ 54 ], adherence rates are low, in part due to uncertain benefits and harms.…”

Childhood cancer survivors face markedly worse overall survival after diagnosis with breast cancer, melanoma, or colorectal cancer

“…In addition, it is unclear whether SM in CCS, which may be associated with prior radiation and chemotherapy exposure, may be biologically different from malignancies arising de novo. One prior database study did not detect differences in receptor expression in breast tumors of CCS relative to the general public, 16 but spontaneous chromosomal abnormalities and differences in expression of DNA‐repair genes in CCS diagnosed with a SM have been reported 17,18 …”