# Immune biological differences between Triple Negative Breast Cancer in African American and non-African American women and potential immunotherapy opportunities to improve treatment outcome

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $474,931

## Abstract

Abstract / Project Summary:
Triple negative breast cancer (TNBC) is more common among African American (AA) women
compared to other races and the survival rates are lower even after adjusting for socio-
economic factors. Recently, we also demonstrated that response rates to preoperative
(neoadjuvant) chemotherapy are also lower indicating lower chemotherapy sensitivity of TNBC
in AA patients. The biological bases of these differences in treatment sensitivity and prognosis
are currently unknown. Immune cell infiltration of TNBC has been shown to be associated with
both prognosis and chemotherapy sensitivity across all races. High level of immune cell
infiltration predicts for greater chemotherapy sensitivity and better survival. Laboratory studies
also demonstrated that activation of anti-tumor immune cells in the cancer microenvironment
during chemotherapy contribute to the cytotoxic effects of the treatment. Racial differences in
immune infiltration of TNBC have not been studied. We hypothesize that the lower
chemotherapy sensitivity of TNBC in AA patients may be due to lower immune cell presence in
these cancers compared to non-AA patients. We also hypothesize that adding an immune
“boosting” drug to standard of care chemotherapy will increase the efficacy of treatment.
The goals of this study are (i) to compare the immune environment of newly diagnosed, stage I-
III, TNBC in AA and non-AA patients and (ii) test in a therapeutic clinical trial if addition of the
anti-PDL1 antibody MEDI4736, to preoperative nab-paclitaxel and dose dense
doxorubicin/cyclophosphamide chemotherapy could increase the rate of complete eradication of
cancer from the breast and lymph nodes (i.e. pathologic complete response rate). This will be
the first study to systematically examine the immune cell composition in TNBC in different racial
groups and the first prospective clinical trial to test if adding immune checkpoint inhibitor therapy
to neoadjuvant chemotherapy could improve response rates in AA patients and if the benefit
from immune therapy differs by race. If our hypothesis is correct and TNBC in AA women have
lower immune cell infiltration which translates into lower chemotherapy sensitivity and poorer
survival, this would provide the basis for developing new immune targeted treatment strategies
to eliminate the outcome difference. Our proposal will also assess one such therapeutic
strategy, inclusion of the anti-PD-L1 antibody, MEDI4736, with standard-of-care neoadjuvant
chemotherapy. Equally importantly, the immune profiling and genomic data that we will generate
will also allow formulating new hypotheses of how one might increase the immunogenicity of
TNBC in AA women, and test such strategies in future clinical trials.
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## Key facts

- **NIH application ID:** 9994235
- **Project number:** 5R01CA219647-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** LAJOS PUSZTAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,931
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994235

## Citation

> US National Institutes of Health, RePORTER application 9994235, Immune biological differences between Triple Negative Breast Cancer in African American and non-African American women and potential immunotherapy opportunities to improve treatment outcome (5R01CA219647-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9994235. Licensed CC0.

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