Abstract P4-09-04: Correlation between histology and molecular subtypes in triple negative breast cancer
Authors: Domingos Tabata Alves , Peixoto Roberto Bonfim Pimenta , Patel Ashka , Taneja Krishan , Chen Wendy Y. , Mittendorf Elizabeth A. , Zimbalist Alexa , Feliciano Elizabeth M. Cespedes , Dillon Deborah A. 
Published: March 2023

Abstract
Correlation between histology and molecular subtypes in triple negative breast cancer Authors: Tabata Alves Domingos, MD; 1* Roberto Bonfim Pimenta Peixoto, MD; 1* Ashka Patel, BS1,2; Krishan Taneja, PhD; 1 Wendy Y. Chen, MD, MPH; 4,5,6 Elizabeth A. Mittendorf, MD, PhD; 5,6,7 Alexa Zimbalist, MS; 3 Elizabeth M. Cespedes Feliciano, ScD SM; 3 Deborah A. Dillon, MD 1,2 *equal contribution Author Affiliations 1. Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115 2. Breast Oncology, Dana-Farber Brigham Cancer Center, Boston, MA 02215 3. Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612 4. Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA 02115 5. Department of Medical Oncology Dana Farber Cancer Institute, Boston, MA 02215 6. Harvard Medical School, Boston, MA 02215 7. Division of Breast Surgery, Brigham and Women’s Hospital, Boston, MA 02215 Background Recently defined molecular subtypes of triple negative breast cancer (TNBC) show distinct clinical outcomes and suggest new therapeutic targets but have not been integrated into current pathologic classification systems. Here, we describe the histopathologic features of TNBC according to four molecular subtypes: basal-like immune activated (BLIA), basal-like immune suppressed (BLIS), luminal androgen receptor (LAR) and mesenchymal (MES), classified using the NanoString BC360 gene expression assay. Methods Stage II and III invasive breast cancers were identified in the Kaiser Permanente (KP) clinical pathology archives (2005-2015) and triple negative status was determined from the KP Northern California Cancer Registry data on immunohistochemistry. Selected slides were reviewed by two pathologists who recorded key histopathologic features [histologic subtype, presence of apocrine, metaplastic or micropapillary features, nuclear grade, mitotic score, and Tumor Infiltrating Lymphocytes (TILs)] and marked the best tumor areas for molecular analysis. TILs were evaluated according to the guidelines of the International TILs Working Group. Cases were macrodissected and evaluated using the NanoString BC360 gene expression assay. Histologic features were then summarized according to molecular subtype. Results Of 72 TNBCs, 60 were classified as Basal-like (83.3%), 7 as HER2-enriched (9.7%) and 5 as Luminal A (6.9%). 41 cases were classified as BLIA (56.9%), 14 as BLIS (19.4%), 13 as LAR (18.0%) and 4 as MES (5.5%). Both BLIA and BLIS tumors showed uniformly high nuclear grade and high mitotic score but differed significantly in TILs (BLIA average 32% vs BLIS average 9%; p value&lt; 0.001, t-test for mean difference in TILs). The majority of LAR cases (69%) showed apocrine differentiation, not present in any other molecular subtype (p value&lt; 0.001, chi-square test for presence of apocrine differentiation). LAR cases showed high nuclear grade but a lower average mitotic score (average score of 2) compared with the basal-like subtypes. TILs in LAR tumors were intermediate (17%) between BLIA and BLIS tumors. Of the 4 MES cases, all showed high nuclear grade. TILs in the MES cases were also intermediate (14%) between BLIA and BLIS tumors. Other histologic features, including lobular subtype, metaplastic and micropapillary features were not associated with specific triple negative molecular subtypes. Conclusion TILs are high in the BLIA molecular subtype (average 32%), low in the BLIS subtype (average 9%) and intermediate in LAR (average 17%) and MES (average 14%) subtypes. Apocrine features, if present in a TNBC, are a strong predictor of LAR molecular subtype. The inclusion of TILs and apocrine features (both easily derived from H&E slides) in routine pathology reporting could improve the classification of TNBC and aid in the identification of patients more likely to respond to specific therapies for the BLIA, BLIS and LAR subtypes, especially in resource-limited settings.
Citation Format: Tabata Alves Domingos, Roberto Bonfim Pimenta Peixoto, Ashka Patel, Krishan Taneja, Wendy Y. Chen, Elizabeth A. Mittendorf, Alexa Zimbalist, Elizabeth M. Cespedes Feliciano, Deborah A. Dillon. Correlation between histology and molecular subtypes in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-09-04.