Association Between Benign Breast Disease in African American and White American Women and Subsequent Triple-Negative Breast Cancer

Abstract

Importance African American (AA) women have a two-fold higher incidence of breast cancers that are negative for estrogen receptor, progesterone receptor and HER2/neu (triple negative breast cancer, TNBC) compared with White/Caucasian Americans (WA). TNBC likely arises from different pathogenetic pathways compared to non-TNBC, and benign breast disease (BBD) predicts for future non-TNBC. Objective To determine whether AA identity remained associated with TNBC among women with a prior diagnosis of BBD. Design Retrospective analysis; January 1, 1994-December 31, 2005; mean follow-up 10.2 years. Setting Henry Ford Health System in metropolitan Detroit, Michigan; an integrated multihospital, multispecialty health care system. Participants 2,588 AA and 3,566 WA patients age 40-70 years with biopsy-proven BBD diagnosed 1/1/1994 to 12/31/2005. Main Outcome Measures Subsequent breast cancer, stratified by phenotype. Results BBD detection and management were similar for the AA and WA patients. Subsequent breast cancers developed in approximately 4% of AA patients (mean 6.8 years following BBD diagnosis) and WA patients (mean 6.1 years). More than three-quarters of subsequent cancers in each subset were DCIS or Stage I. The 10-year probability estimate for developing TNBC was 0.56% (95% confidence interval 0.32-1.0) for AA versus 0.25% for WA (95% confidence interval 0.12-0.53). Among the 73 AA patients that developed subsequent invasive breast cancer, 24.2% were TNBC compared to 7.4% of the 111 subsequent invasive BC cases (p=0.0125) among the WA patients. Conclusion and Relevance AA identity persisted as a significant risk factor for TNBC in our study, the largest analysis to date of BBD and subsequent breast cancer phenotypes in a diverse patient population managed equitably. This suggests that AA identity is associated with inherent susceptibility for TNBC pathogenetic pathways.

Associations of race and ethnicity with risk of developing invasive breast cancer after lobular carcinoma in situ

“…Thus, the magnitude of the associations between black race and risk of invasive breast cancer subtypes following LCIS and DCIS was similar. Among women with benign breast disease, African American identity was a significant risk factor for triple negative breast cancer [25]. These findings warrant further investigation of race-related biomarker profiling of pre-malignant breast lesions.…”

Pan‐cancer clinical and molecular analysis of racial disparities

“…4 Many factors contribute to disparities in cancer outcomes, including socioeconomic factors, culture, diet, stress, and the macroenvironment. 9 A comparison of TNBC in AA versus EA patients has demonstrated a gene expression signature consistent with increased loss of BRCA1 expression, increased activation of insulin-like growth factor 1 receptor, and increased expression of vascular endothelial growth factor-activated genes in AA patients. However, other observations suggest a role for molecular differences in cancer survival disparities.…”

“…8 Compared with EA women, AA women have a 2-fold higher incidence of the inherently aggressive triple-negative breast cancer (TNBC). 9 A comparison of TNBC in AA versus EA patients has demonstrated a gene expression signature consistent with increased loss of BRCA1 expression, increased activation of insulin-like growth factor 1 receptor, and increased expression of vascular endothelial growth factor-activated genes in AA patients. 10 In addition, AA patients with breast, head and neck, or endometrial cancer have higher levels of chromosomal instability and frequency of TP53 mutations and CCNE1 amplification than white patients.…”

Patient-Derived Xenografts as an Innovative Surrogate Tumor Model for the Investigation of Health Disparities in Triple Negative Breast Cancer

“…3 TNBC mortality is more pronounced in patients of African and Hispanic ancestries, suggesting specific contributing factors within these patients cohorts contributes to overall survival and prognoses. [4][5][6][7][8] Socioeconomic factors (low income and poor access to health care) in these patient cohorts significantly affects TNBC incidence and mortality outcomes in Black and Hispanic populations, more so than in non-Black and non-Hispanic populations, referenced as White populations throughout this review.…”