Clinical outcome of triple-negative early breast cancer in a non-African American women cohort: More fuel to the fire.

Breast cancer is the most commonly diagnosed cancer worldwide and remains the second leading cause of cancer death. While breast cancer mortality has steadily declined over the past decades through medical advances, an alarming disparity in breast cancer mortality has emerged between African American women (AAW) and Caucasian American women (CAW); and new evidence suggests more aggressive behavior of triple-negative breast cancer (TNBC) in AAW may contribute to racial differences in tumor biology and mortality. Progesterone (PRG) is capable of exerting its cellular effects through either its classic, non-classic or combined responses through binding to either classic nuclear PRG receptors (nPRs) or non-classic membrane PRG receptors (mPRs), warranting both pathways an equally important status in PRG-mediated signaling. In our previous report, we demonstrated that the CCM signaling complex (CSC) consisting of CCM1, CCM2, and CCM3 proteins can couple both nPRs and mPRs signaling cascades to form a CSC-mPRs-PRG-nPRs (CmPn) signaling network in nPR positive(+) breast cancer cells. In this report, we furthered our research by establishing the CSC-mPRs-PRG (CmP) signaling network in nPR(-) breast cancer cells, demonstrating that a common core mechanism exists, regardless of nPR(+/-) cell type. This is the first report stating that inducible expression patterns exist between CCMs and major mPRs in TNBC cells. Furthermore, we firstly show mPRs in TNBC cells are localized in the nucleus and participate in nucleocytoplasmic shuttling in a coordinately synchronized fashion with CCM proteins under steroid actions, following the same cellular distribution as other well-defined steroid hormone receptors. Finally, for the first time, we deconvoluted the CmP signalosome by using multi-omics approaches, which helped us understand key factors within the CmP network, and identify 21 specific biomarkers with potential clinical applications associated with AAW-TNBC tumorigenesis. These novel biomarkers could have immediate clinical implications to dramatically improve health disparities among AAW-TNBCs.

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Triple negative breast cancer in African American women: Disparity between women in New Orleans versus Louisiana.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e12501 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e12501-e12501 ◽

Cited By ~ 1

Author(s):

Michelle Marie Loch ◽

John Estrada ◽

Thomas Reske ◽

Xiangrong Li ◽

Vivien Chen ◽

...

Keyword(s):

Breast Cancer ◽

African American ◽

African American Women ◽

New Orleans ◽

White Women ◽

Triple Negative ◽

Her2 Status ◽

Tumor Characteristics ◽

Empirical Observation ◽

American Women

e12501 Background: For years clinicians have made the empirical observation that there is an unusually high number of African American women (AAW) with triple-negative (Tneg) breast cancer (BC) in New Orleans (NO). Knowing the rate of Tneg BC in AAW is higher than white women (WW), we explored the hypothesis that AAW in NO have a higher rate of Tneg BC when compared to AAW in the rest of Louisiana (LA). Methods: We analyzed data from the Louisiana Tumor Registry, one of the NCI funded SEER registries, for the tumor characteristics of invasive female BC diagnosed in 2010, focusing on racial disparities; HER2 status was not available for prior to 2010 diagnosis. We explored the association of HER2 status with age, race, ER, PR, HER2, T, N, M to determine crude and adjusted odds ratios and rate distribution of subtypes using SEER*Stat and SAS programs. Results: Overall age-adjusted incidence rate of Tneg BC in AAW was 30 per 100,000 in NO, which was 24% higher than that in AAW in the rest of LA and two-fold the rate in WW of both NO and LA. The highest rate of Tneg BC was seen in AAW aged 65-69 in NO (184.97 per 100,000) compared with 81.5 per 100,000 in AAW aged 55-59 in LA. AAW with Tneg BC in NO were more likely to have more aggressive BC. Young age, black race, large tumor size, higher grade and TNM stage were significantly associated with the high risk of Tneg BC. After adjusting for age, geographic area, and other tumor characteristics, the higher risk of Tneg BC in AAW remained in NO compared with the rest of LA (OR=1.4; 95% CI: 1.01-1.87). Conclusions: AAW in NO are more likely to have poorly differentiated and Tneg BC compared to AAW in the rest of LA. This disparity remains when comparing our data to previously published literature in other parts of the US. We plan to continue our data analysis and compare NO data to the national average as the HER2 data become available in the SEER Program to better characterize the disparity. This newly identified disparity in the AAW population in NO has clinical implications and translational research potential as it enables us to broaden the understanding and treatment of this aggressive disease.

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