Abstract C49: Relation of family history of cancer to risk of ER+, ER-, and triple-negative breast cancer in African American women
Authors: Bethea Traci N. , Rosenberg Lynn , Castro-Webb Nelsy , Lunetta Kathryn L. , Sucheston Lara E. , Ruiz-Narvaez Edward A. , Charlot Marjory , Park Song Y. , Bandera Elisa V. , Troester Melissa A. , Ambrosone Christine B. , Palmer Julie R. 
Published: May 2016

Introduction: Family history of breast cancer has been shown to be a strong risk factor for breast cancer in all populations studied. However, there are limited data related to risk of estrogen receptor negative (ER-) breast cancer in African American women, who have a disproportionately high incidence of ER- and triple negative (ER-, progesterone receptor negative, and HER2 receptor negative; TN) breast cancer. Even less information is available on whether a family history of other cancers also affects risk of ER- and TN breast cancer.

Methods: Questionnaire data from the Black Women's Health Study, the Carolina Breast Cancer Study, the Multiethnic Cohort Study, and the Women's Circle of Health Study were pooled as part of the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Breast cancer cases were classified as ER+, ER-, and TN based on pathology data from medical records and/or state cancer registries. Participants were asked about first degree relatives with a breast cancer diagnosis and the age at which the relative was diagnosed. Participants were also asked about first degree relatives with prostate, lung, colorectal, ovarian, or cervical cancer or with lymphoma or leukemia. Polytomous logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for various categories of positive family history relative to no first degree relative with breast cancer or no first degree relative with any of the cancers. Multivariable analyses controlled for age, study, time period, and other potential confounders.

Results: The analysis included 3,023 African American women with ER+, 1,497 with ER-, and 696 with TN breast cancer and 17,420 controls. First degree family history of breast cancer, regardless of whether first degree relatives had cancers other than breast cancer, was associated with a 70% increased risk of ER+, ER- and TN breast cancer; the ORs were 1.7 (95% CI 1.6-2.0) for ER+, 1.7 (95% CI 1.4-1.9) for ER-, and 1.7 (95% CI 1.4-2.1) for TN breast cancer. The ORs were somewhat higher if the relative was diagnosed before age 50 (2.0 for ER+, 1.9 for ER-, and 1.8 for TN). Among the six other cancer sites examined, only family history of cervical cancer was significantly associated with risk; the ORs were 2.4 (1.4-4.2) for ER- and 2.9 (1.5-5.5) for TN breast cancer and there was no association with ER+ breast cancer. The OR for family history of ovarian cancer in relation to TN breast cancer was 1.6 (0.9-2.7), which is of interest because findings from The Cancer Genome Atlas (TCGA) indicate that serous ovarian cancers and basal-like breast cancers, which are mostly triple negative, have many molecular commonalities. The ORs for a family history of both breast and prostate cancer versus no family history of any of the cancers were 3.4 (2.4-4.7) for ER+ cancer, as compared with 1.6 for breast alone (p-interaction=0.01), and 2.1 (1.2-3.7) for ER- cancer, as compared with 1.5 for breast alone (p-interaction=0.08). The OR for a family history of both breast and lung cancer was 3.3 (1.9-5.9) for TN breast cancer, compared to 1.5 for breast alone (p-interaction=0.10). The ORs for family history of breast plus two other cancers were 2.4 (1.6-3.6) for ER+, 2.8 (1.6-4.7) for ER-, and 2.7 (1.3-5.7) for TN breast cancer.

Conclusion: Our results confirm that having a first degree family history of breast cancer is a strong risk factor for ER+, ER-, and TN breast cancer. The findings also suggest that having relatives with other cancers in addition to a relative with breast cancer may further increase risk. Consideration of family history of other cancers may improve risk prediction models. The association observed for family history of cervical cancer and increased risk of ER- and TN breast cancer was unexpected and needs to be replicated by other studies.

Citation Format: Traci N. Bethea, Lynn Rosenberg, Nelsy Castro-Webb, Kathryn L. Lunetta, Lara E. Sucheston, Edward A. Ruiz-Narvaez, Marjory Charlot, Song Y. Park, Elisa V. Bandera, Melissa A. Troester, Christine B. Ambrosone, Julie R. Palmer. Relation of family history of cancer to risk of ER+, ER-, and triple-negative breast cancer in African American women. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C49.