Abstract
BACKGROUND: Adverse events in childhood are linked to cancer risk across the life course, but evidence is lacking regarding parental death during childhood and breast cancer characteristics. We investigated whether women who experienced parental loss in childhood have a higher incidence of breast cancer and are at higher risk of aggressive disease. METHODS: The Child Health and Development Studies (CHDS) consists of more than 15 000 families that enrolled during mothers' pregnancies between 1959 and 1967; family members were followed for cancer incidence and cause-specific mortality. We constructed an analytical cohort of all live-born CHDS daughters (N = 9169) linked to their parents' cause and date of death. We estimated adjusted hazard ratios of incident breast cancer, disease stage at diagnosis, and tumor hormone receptor expression for parental loss in Cox models adjusted for race, maternal breast cancer, and paternal age. Generalized linear models estimated associations between breast density and parental loss among a subsample of CHDS daughters (n = 610) with available mammography reports. RESULTS: In total, 137 CHDS daughters were diagnosed with breast cancer by age 52 years, and 654 daughters had lost 1 or both parents when they were 21 years of age or younger. Loss of both parents was associated with breast cancer incidence (adjusted hazard ratio = 4.69, 95% CI = 1.68 to 13.04); late-stage disease at diagnosis (adjusted hazard ratio = 9.47, 95% CI = 1.38 to 64.84); and ERBB2 (formerly HER2)-positive, progesterone receptor-negative, and estrogen receptor-negative tumors. Loss of mother or father was associated with ERBB2-positive tumors. Breast density in the premenopause window was associated with loss of a mother or both parents. CONCLUSION: In a multigenerational cohort with well-defined cancer outcomes and validated cause-of-death data, life-course risk of breast cancer was 4.69 times higher among participants who had lost both parents during childhood. Subanalyses showed that parental loss was associated with late stage at diagnosis and tumor hormone markers of aggressive disease. Parental death during childhood could be added to medical histories to indicate a need for counseling on prevention and early detection of breast cancer.