Abstract PO5-01-08: The impact of Human Epidermal growth factor Receptor 2 (HER2) expression by RT-PCR on tumor characteristics and outcome in estrogen receptor (ER) positive, HER2 negative early-stage breast cancer
Authors: Hadar Goldvaser, Raz Mutai, Salomon Stemmer, Iryna Kuchuk, Margarita Tokar, Shani Paluch-Shimon, Rinat Yerushalmi, Karen Drumea, Ella Evron, Amir Sonnenblick, Einav Gal-Yam, Gil Bar Sela, Ayelet Shai, Rotem Merose, Avital Bareket-Samish, Lior Soussan-Gutman
Journal: Cancer Research (2024)

Abstract Background: The role of HER2 expression in HER2 negative breast cancer is evolving. Whether HER2 expression has an impact on ER positive, HER2 negative early-stage breast cancer in unclear. Oncotype DX assay Recurrence Score comprises of standardized quantitative HER2 mRNA expression levels by RT-PCR. The objective of this study was to investigate the impact of Oncotype HER2 score on tumor characteristics and outcome. Methods: All women assigned to the Clalit Health Services registry between 2006 to 2011 with ER positive, HER2 negative early-stage breast cancer whose tumor were sent for oncotype were identified. Patients in which HER2 score was reported in the oncotype results were included. Differences in age, tumor characteristics and chemotherapy administration between lower HER2 score (H1), i.e. HER2 score ≤ 9.1, to higher HER2 score (H2), i.e. 9.2-10.7, were analyzed. 5-year Kaplan–Meier for distant recurrence free survival (DRFS) and overall survival (OS) were estimated and differences between H1 and H2 were evaluated. Analyses were repeated separately for node negative and for node positive (N mic and 1-3 lymph nodes) disease. Results: A total of 1535 patients were included, 948 patients with node negative disease and 587 with node positive disease. Of these, 814 and 721 patients were categorized to the H1 and H2 groups, respectively. Median follow-up was 5.4 years. The distribution of oncotype RS was different, with significantly lower proportion of patients with RS between 0-10 and higher proportion of RS above 25 in the H1 group compared to the H2 groups. This difference was identified both for patients with node negative and node positive disease (Table). The distributions of age, tumor size and histological subtype were comparable between the H1 and the H2 groups, both for node negative and node positive disease. Within each RS group, administration of chemotherapy was comparable between H1 and H2 groups, regardless of nodal involvement. DRFS and OS were not associated with HER2 score. For RS 0-25, node negative disease, 5-year DRFS was 96.2% in H1 and 96.4% in H2 groups (p=0.92) and 5-year OS was 97.2% in H1 and 98.1% in H2 groups (p=0.39). For RS &amp;gt;25, node negative disease, 5-years DRFS was 89% in H1 and 90.8% in H2 groups (p=0.33) and 5-year OS was 90.6% in H1 and 90.8% in H2 groups (p=0.7). Similarly, for node positive disease, DRFS and OS were comparable between H1 and H2 group in all subgroups. Conclusions: Low HER2 mRNA expression by Oncotype RT-PCR assay was associated with significantly high Oncotype RS. Patients' outcome was not directly affected by HER2 score and was determined by RS. Further study is desired to clarify the role of HER2 expression in early stage, luminal breast cancer. Table. Comparison of age and tumor characteristics between low (H1) and high (H2) HER2 score Citation Format: Hadar Goldvaser, Raz Mutai, Salomon Stemmer, Iryna Kuchuk, Margarita Tokar, Shani Paluch-Shimon, Rinat Yerushalmi, Karen Drumea, Ella Evron, Amir Sonnenblick, Einav Gal-Yam, Gil Bar Sela, Ayelet Shai, Rotem Merose, Avital Bareket-Samish, Lior Soussan-Gutman. The impact of Human Epidermal growth factor Receptor 2 (HER2) expression by RT-PCR on tumor characteristics and outcome in estrogen receptor (ER) positive, HER2 negative early-stage breast cancer [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 PO5-01-08.