Abstract PO5-02-09: Discordance of the PAM50 intrinsic subtypes with the immunohistochemistry-based subtypes in HER2-negative early breast cancer treated with neoadjuvant chemotherapy

Abstract

Abstract Background The PAM50 (Prosigna Breast Cancer Gene Signature Assay) can be used to assess the expression levels of 50 genes in early breast cancer biopsies, including formalin-fixed paraffin-embedded (FFPE) tissue from human epidermal growth factor receptor 2 (HER2)-negative patients. However, there is currently no practical molecular assay for intrinsic subtype in real-world practice that addresses the problems of cost and run-time. Methods In the phase 2 HER2E-PAM/PAMILIA study (NCT04817540), we prospectively analyzed molecular subtyping through the PAM50 test in low HER2 (HER2 IHC 1+ or 2+ SISH-) breast cancer patients. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. This study was originally designed to determine whether adding HER2-targeted treatment in HER2 enriched molecular subtype increases the pathologic complete rate (pCR). We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping of pre- & post-operative tissues and PAM50 intrinsic subtypes, and to assess the pCR according to the discordance. Results In a total 82 patients, the proportions of HR+/HER2- and triple negative breast cancer (TNBC) in the preoperative tissue were 85.4% (n=70) and 14.6% (n=12), respectively. According to PAM50 intrinsic subtypes, 11.0% (n=9) were basal, 8.5% (n=7) were HER2-enriched, 34.1% (n=28) were luminal A, 36.6% (n=30) were luminal B, and 3.7% (n=3) were normal-like type. In total, 32 patients (41.5%) were discordant between IHC-based preoperative subtype and PAM50 intrinsic subtype. Among the 70 patients with HR+/HER2-, non-luminal A, B type was found in 12.9% with basal-like, 8.6% with HER2-enriched, and 4.3% with normal-like type, respectively. Of 12 TNBC patients, 83.3% were luminal A, B type, and 8.3% were HER2-enriched. In the other hands, 6 patients (13.0%) were discordant between IHC-based post-operative subtype and PAM50 intrinsic subtype. Among the 40 patients with HR+/HER2- postoperative subtype, non-luminal A, B type was found in 2.5% with basal-like, 2.5% with HER2-enriched, and 5.0% with normal-like type, respectively. Of 6 TNBC postoperative patients, 16.7% were normal-like. Most received anthracycline- and taxane-based neoadjuvant chemotherapy. During data analysis (June 2023), 54 cases underwent surgery after neoadjuvant chemotherapy. 4 of 54 patients (7.4%) achieved a pCR, of which one was HER2-enriched, one was luminal B-like, and two were basal-like PAM50 intrinsic subtype. However, discordance of IHC based subtype with intrinsic subtype was not considerable and was not correlated with pCR. Conclusion A substantial portion of patients showed discrepancy between preoperative and postoperative IHC subtype and PAM50 intrinsic subtype in our study. Citation Format: Jee Hung Kim, Soong June Bae, Sung Gwe Ahn, Jeonghee Lim, Min Hwan Kim, Gun Min Kim, Joo Hyuk Sohn, Joon Jeong. Discordance of the PAM50 intrinsic subtypes with the immunohistochemistry-based subtypes in HER2-negative early breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-09.