Time to Diagnosis of Second Primary Cancers among Patients with Breast Cancer (BRCA)

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Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of
Doctor of Philosophy Public Health

Abstract
Many breast cancer diagnoses and second cancers are associated with BRCA gene
mutations. Early detection of cancer is necessary to improve health outcomes,
particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading to the development of cancer. Composite endpoint was used to define second primary cancer occurrences, and Kaplan- Meier survival curves were used to compare the median time-to-event among comparison groups and BRCA gene mutation status. Cox proportional hazards was used to examine the relationships between age at diagnosis, ethnicity, BRCA gene mutation status, and diagnosis of a second primary cancer. The overall median time to event for diagnosis of
second primary cancers was 14 years. The hazard ratios for BRCA2 = 1.47, White = 1.511, and American Indian/Hawaiian = 1.424 showed positive significant associations between BRCA2 mutation status and risk of diagnosis of second primary colorectal, endometrial, cervical, kidney, thyroid, and bladder cancers. Data on risk factors for development of second cancers would allow for identification of appropriate and timely screening procedures, determining the best course of action for prevention and treatment, and improving quality of life among breast cancer survivors.

Second cancers: For the purpose of this study, second cancer refers to any cancer
that a patient experienced after initial diagnosis with BRCA1- or BRCA2-related breast cancer.