Parental loss at age 0-21 and daughters' breast cancer and tumor characteristics.

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 (BrCa) characteristics. We investigated whether parental loss in childhood defines women at higher risk of BrCa incidence and aggressive disease.

Methods: The Child Health and Development Studies (CHDS) comprises over 15,000 families who enrolled during mothers' pregnancies between 1959-1967; family members were followed for cancer incidence and cause-specific mortality. We constructed an analytical cohort of all live-born CHDS daughters (N = 9,169), linked to their parents' cause and date of death. We estimated adjusted hazard ratios of incident BrCa, stage at diagnosis, and tumor hormone receptor expression for parental loss in Cox models adjusted for race, maternal BrCa, and paternal age. Generalized linear models estimated associations between breast density and parental loss among a subsample CHDS daughters (N = 610) with available mammography.

Results: 137 CHDS daughters were diagnosed with BrCa by age 52, and 654 daughters lost one or both parents at age ≤21. Loss of both parents was associated with BrCa incidence [aHR(95%CI)=4.69(1.68,13.04)], late-stage at diagnosis [aHR(95%CI)=9.47(1.38,64.84)], and HER2-positive, PR-negative, and ER-negative tumors. Loss of mother or father was associated with HER2-positive tumors. Breast density in the premenopause window was associated with loss of mother or both parents.

Conclusion: Death of one or both parents during childhood was strongly associated with BrCa and aggressive disease. Parental death during childhood could be added to medical histories to indicate counseling regarding prevention and early detection of BrCa.