# Research Pilot Project

> **NIH NIH P20** · H. LEE MOFFITT CANCER CTR & RES INST · 2020 · $96,957

## Abstract

ABSTRACT – Research Pilot
Breast cancer is the most frequent malignancy in women worldwide, yet there are pronounced differences in
incidence and mortality between racial/ethnic groups. Hispanics/Latinas (H/L) are a growing and understudied
group characterized by a variable admixture of European, Indigenous American, and African ancestry. Breast
cancer is genetically and biologically heterogeneous, consisting of multiple molecular subtypes which differ in
terms of prognosis and response to treatment. The PAM50 gene expression panel distinguishes five main
intrinsic subtypes of breast cancer: Luminal A, Luminal B (both ERα-positive), Her2/Neu enriched, Basal-like
and Normal-like. The Luminal B subtype has a poorer prognosis than Luminal A, lower expression of nuclear
hormone receptors, and higher expression of proliferation markers. These tumors benefit less from endocrine
therapy, and remain the largest cause of breast cancer mortality. In a cohort of 301 clinically annotated H/L
breast cancer patients, we found that among mixed-ancestry Hispanic/Latina patients, the frequency of
Luminal B tumors is remarkably high (>42%). Among these H/L patients, Luminal B tumors are characterized
by a more aggressive clinical presentation than Luminal A tumors, suggesting that the high frequency of
Luminal B tumors is associated with a strong health outcomes disparity. A higher incidence of Luminal B
tumors has been reported among US H/L patients, but the number of H/L in the study was too small to draw
definite conclusions. Using RNASeq, we found that H/L Luminal B tumors are frequently characterized by
increased expression of the ERBB2 (Her2/Neu) receptor, the GRB7 adaptor and the migration and invasion
enhancer, MIEN1. Expression of these three genes was linked to Indigenous American (IA) ancestry and all
are located at Ch17q12. ERBB2 and GRB7 are co-amplified in Her2/Neu enriched tumors, and are correlated
with endocrine resistance and poor prognosis in ERα-positive tumors. A link between genetic ancestry and
Luminal B breast cancer can help identify prognostic biomarkers as well as molecular features for specific
therapeutic approaches (precision medicine) in H/L. Our primary hypothesis is that H/L ethnicity/IA ancestry
are associated with a high incidence of Luminal B tumors and with increased expression of ERBB2, GRB7 and
MIEN1. Furthermore, we propose that the elevated expression of these three genes may be the consequence
of altered promoter or enhancer methylation linked to IA ancestry. To test these ideas, we will examine a novel
cohort of H/L breast cancer patients in two specific aims: (1) to determine the molecular portraits of PAM50-
confirmed Luminal B tumors from H/L breast cancer patients utilizing RNASeq, and to correlate these findings
with clinicopathological parameters and outcomes, and (2) to establish the relationship of ERBB2, GRB7 and
MIEN1 with promoter methylation, ancestry, clinicopathological parameters and clinical outcomes.

## Key facts

- **NIH application ID:** 10005162
- **Project number:** 5P20CA202920-04
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** William Douglas Cress
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $96,957
- **Award type:** 5
- **Project period:** 2017-09-21 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005162

## Citation

> US National Institutes of Health, RePORTER application 10005162, Research Pilot Project (5P20CA202920-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10005162. Licensed CC0.

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