Abstract PO4-24-12: Premenopausal breast cancers show higher proportion of immunologically cold tumors and are associated with distinct immune cell infiltrate

• Published in: Cancer research (Chicago, Ill.) Vol. 84; no. 9_Supplement; p. PO4-24-12
• Main Authors: Nimbalkar, Vidya P, VP, Snijesh, Rajarajan, Savitha, Alexander, Annie, Ramesh, Rakesh, Srinath, B S, Prabhu, Jyothi S
• Format: Journal Article
• Language: English
• Published: 02.05.2024
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.SABCS23-PO4-24-12

Abstract Background Breast cancers (BC) in the young women tend to have poor outcomes and higher proportion of aggressive subtypes. Immunotherapy has shown promising results lately, especially for aggressive categories like triple negative breast cancers (TNBC). Success of the immunotherapy is shown to be dependent on the tumor immune microenvironment (TIME) which plays important role in disease progression and response to therapy. Though numerous studies have demonstrated immune hot tumors are associated with better prognosis, mechanism of immunologically hot TIME is not yet deciphered. Material and methods Gene expression data derived from RNA sequencing (n=40) of primary BC was used to divide them into immune hot and cold tumors by using 15 gene signature (Wang et al., Sci. Adv. 2021). Average expression of the hot and cold (hot=12 and cold=3) genes was derived for each tumor and median value of their ratio was used to categorize them into immunologically hot and cold tumors. Association of the hot and cold tumors with clinical characteristics was examined. CIBERSORT algorithm was used to identify immune cell subtypes and Kaplan Meier survival analysis was performed to assess the prognostic significance. Similar analysis was replicated in TCGA (n=1083) dataset. Results Equal proportion of immune hot and cold tumor was observed in the cohort. Higher proportion of cold tumors were observed in younger and premenopausal (p=0.002) patients. Subtype analysis showed higher proportion of cold tumors in TNBC compared to hormone receptor positive tumors (p< 0.0001). No significant difference was observed in other clinicopathological characteristics between the groups. Further analysis of cold tumors for immune cell subtypes, categorized by the menopausal status showed higher proportion of plasma cells and CD4 memory resting cells and lower proportion of M2 macrophages and B memory cell in premenopausal (n=129, TCGA) compared postmenopausal (n=322, TCGA) tumors. In addition, premenopausal cold tumors were associated with better overall survival compared to postmenopausal group (p=0.001). Conclusion Younger premenopausal women with BC are likely to have more immunologically cold tumors. Though circulating levels of sex steroid hormones is the predominant difference between the pre and postmenopausal women, its influence on TIME and therapeutic significance must be explored. Citation Format: Vidya P Nimbalkar, Snijesh VP, Savitha Rajarajan, Annie Alexander, Rakesh Ramesh, B S Srinath, Jyothi S Prabhu. Premenopausal breast cancers show higher proportion of immunologically cold tumors and are associated with distinct immune cell infiltrate [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 PO4-24-12.