p27 Loss Correlates With High-Grade Advanced Stage Triple Negative Breast Ductal Cancers in African-American Women

e18074 Background: Approximately 12% of breast cancer cases occur in women younger than 50 years, per SEER data from 2012. Hispanic women are known to present at a younger age and African American women with more advanced stage disease. In this study, we describe the impact of age and race on the initial presentation of breast cancer among minority women treated at the Hennepin Healthcare System (HHS) in the state of Minnesota. Methods: A single-institution retrospective analysis of data from our electronic health record of all breast cancer diagnoses from 2010-2015. Cases were compared by age ( < 50 or > 50 years), race (Caucasian, African American, Hispanic, other), stage (AJCC 7th edition), and method of diagnosis (self-reported mass or screening mammography). Results: A total of 315 breast cancer diagnoses occurred at HHS from 2010-2015. In our cohort, 29% of all breast cancer cases were diagnosed in women < 50yrs. Hispanic and African American women had higher rates of diagnosis at < 50yrs compared to Caucasian women (38.9% vs 37.1% vs 18.1 respectively, p < 0.05). Early stage cancer (stage 0 or I) accounted for most diagnoses in those > 50yrs (54.8%), while advanced stage (stage II-IV) was more prevalent in the < 50yrs age group (59.5%) (p < 0.05). Of all women diagnosed with breast cancer, 63% presented with a self-reported mass and 37% were diagnosed by screening mammography. Hispanics and African American women had a higher rate of presentation with a self-reported mass (74% and 66% respectively) compared to Caucasian women (55%). Women with breast cancer < 50yrs were more likely to present with a self-reported mass than women > 50yrs (80% vs 55%, p < 0.05). 92% of Hispanic and 80% of African American women < 50yrs presented with a self-reported mass, compared to 62% of Caucasian women (p = 0.095). Conclusions: At our institution, Hispanic and African American women are diagnosed at a significantly younger age than Caucasian women, and those diagnosed at a younger age have more advanced disease. Presenting with a self-reported mass is very common for young non-Caucasian women. Whether screening mammography can be better utilized to change these trends requires further study.

Download Full-text

CmP signaling network unveils novel biomarkers for triple negative breast cancer in African American women

10.1101/2021.05.24.445510 ◽

2021 ◽

Author(s):

Johnathan Abou-Fadel ◽

Brian Grajeda ◽

Xiaoting Jiang ◽

Alyssa-Marie Cailing-De La O ◽

Esmeralda Flores ◽

...

Keyword(s):

Breast Cancer ◽

African American ◽

African American Women ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Breast Cancer Mortality ◽

Signaling Network ◽

American Women ◽

Novel Biomarkers

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.

Download Full-text