Abstract PS7-12: Impact of race/ethnicity on triple negative breast cancer molecular features, treatment response and clinical outcomes in patients receiving neoadjuvant therapy
Authors: Teshome Mediget , Sun Ryan , Ravenberg Elizabeth E. , Brewster Abenaa , Chavez-MacGregor Mariana , White Jason B. , Moulder Stacy 
Published: February 2021

Background: Triple negative breast cancer (TNBC) disproportionally impacts Black and Hispanic women and is suggested to be partly responsible for disparities observed in breast cancer mortality. We sought to evaluate the impact of race/ethnicity on TNBC molecular subtype, immune profile, pathologic complete response (pCR) and recurrence free survival (RFS).

Methods: The ARTEMIS trial (NCT02276443) uses imaging response and molecular profiling to personalize neoadjuvant chemotherapy in early stage TNBC. After 4 cycles of AC, patients with chemo-sensitive disease receive standard taxane-based therapy, while those with chemo-resistant disease are offered therapeutic trials based upon molecular profiling. Pathologic response was assessed at surgery. Patients self-reported race/ethnicity was categorized as Asian, Black/African-American, Hispanic/Latino and White (non-Hispanic). Patients were excluded if no race or ethnicity was reported. Clinical and pathologic factors were recorded and compared. Gene expression profiling was performed by RNAseq to determine Vanderbilt signature. PD-L1 and Androgen Receptor (AR) were determined by immunohistochemistry. Frequencies at which various factors were observed by race/ethnicity were calculated and Fisher’s exact test performed to determine statistical significance. Kaplan-Meier analysis was used to estimate survival stratified by pCR status and race/ethnicity.

Results: Among 321 women enrolled in ARTEMIS, 26 (8.1%) were classified as Asian, 50 (15.6%) as Black, 59 (18.4%) as Hispanic and 186 (57.9%) as White. Demographic and clinical features were similar, except Black women were more likely to have BMI ≥30 (70.0%, p&lt;0.001). Comparing by race/ethnicity, there was no statistically significant difference in tumor histology, tumor size, nodal status, clinical stage, chemo-resistant disease, type of surgery or receipt of radiation. A trend toward higher proportion of N3 disease was observed in Black women (24.0%) compared to other groups (p=0.054). Tumor profiling results are listed in Table 1. No statistically significant difference was observed by race/ethnicity in Vanderbilt signature, presence of PD-L1 or stromal tumor infiltrating lymphocytes (sTIL) status. More AR-positive tumors were identified in Asian women (64%, p=0.007). pCR and RCB status did not significantly vary by race/ethnicity however, higher proportion of RCB-III disease was identified in Black (14%) and Hispanic women (16.9%) as compared to Asian (3.8%) and White (8.6%) women (p=0.164). At median follow up of 23.8 months (range 3.4-51.1), there was no statistically significant difference in RFS by race/ethnicity.

Conclusion: Among this population of patients with TNBC treated with neoadjuvant chemotherapy there was no statistically significant difference observed in TNBC Vanderbilt signature, PD-L1 staining, sTIL, pCR or RFS by race/ethnicity. Asian women were found to have a higher incidence of AR-positive subtype. Numerically higher rates of N3 stage in Black women and RCB-III classification in Black and Hispanic women were identified, however not statistically significant. Larger cohorts of patients are needed to further investigate these findings.

Table 1. TNBC profiling compared by race/ethnicity.Total n (%)Asian n (%)Black n (%)Hispanic/Latino n (%)White n (%)p valueVanderbilt signature n (%) Basal like (BL1) Basal like 2 (BL2) Immunomodulatory (IM) Luminal androgen receptor (LAR) Mesenchymal (M) Mesenchymal stem-like (MSL) Unstable (UNS)231 50 (21.6) 25 (10.8) 42 (18.2) 22 (9.5) 48 (20.8) 14 (6.0) 30 (13.0)21 (9.1) 0 (0.0) 4 (19.0) 5 (23.8) 3 (14.3) 5 (23.8) 1 (4.8) 3 (14.3)35 (15.2) 9 (25.7) 5 (14.3) 6 (17.1) 2 (5.7) 7 (20.0) 1 (2.9) 5 (14.3)43 (18.6) 14 (32.5) 3 (7.0) 10 (23.2) 5 (11.6) 6 (14.0) 2 (4.7) 3 (7.0)132 (57.1) 27 (20.5) 13 (9.8) 21 (15.9) 12 (9.1) 30 (22.7) 10 (7.6) 19 (14.4)NSAndrogen Receptor n (%) Positive (&gt;=10%) Negative (&lt;10%)311 109 (35.0) 202 (65.0)25 (8.0) 16 (64.0) 9 (36.0)49 (15.8) 11 (22.4) 38 (77.6)57 (18.3) 19 (33.3) 38 (66.7)180 (57.9) 63 (35.0) 117 (65.0)0.007PD-L1 n (%) None &gt;1298 212 (71.1) 86 (28.9)24 (8.1) 15 (62.5) 9 (37.5)47 (15.8) 33 (70.2) 14 (29.8)57 (19.1) 40 (70.2) 17 (29.8)170 (57.0) 124 (72.9) 46 (27.1)NSStromal tumor infiltrating lymphocytes (sTIL) n (%) High (&gt;=20%) Low (&lt;20%)319 107 (33.5) 212 (66.5)26 (8.1) 12 (46.2) 14 (53.8)50 (15.7) 13 (26.0) 37 (74.0)58 (18.2) 21 (36.2) 37 (63.8)185 (58.0) 61 (33.0) 124 (67.0)NS

Citation Format: Mediget Teshome, Ryan Sun, Elizabeth E. Ravenberg, Abenaa Brewster, Mariana Chavez-MacGregor, Jason B. White, Stacy Moulder. Impact of race/ethnicity on triple negative breast cancer molecular features, treatment response and clinical outcomes in patients receiving neoadjuvant therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-12.