Background: The 21-gene OncotypeDX (ODX) assay has been validated as a predictive biomarker in early-stage hormone receptor positive (HR+) and HER2- breast cancer. This multigene panel identifies patients with a high risk of recurrence who would benefit systemic treatment involving both chemotherapy and endocrine therapy, versus endocrine therapy alone. ODX is not indicated in HER2 + breast cancer. Not all patients with HER2+ breast cancer are candidates for anti-HER2 treatments due to the potential for cardiotoxicity. We were interested to assess the value of ODX in predicting benefit of anti-HER2 treatment in HR+ and HER2+ breast cancer. Methods: We used the National Cancer Database to identify patients with early-stage (AJCC clinical staging I-II), HR+/HER2+ breast cancer who happen to have received multigene testing with ODX. We described this cohort using univariate descriptive statistics. We then explored the predictive value of this biomarker by constructing two Kaplan-Meier models for overall survival (OS) with log-rank testing. The first model generates OS curves associated with different approaches to systemic treatment (a. endocrine therapy alone, versus b. endocrine therapy + anti-HER2 targeted treatment, versus c. endocrine therapy + chemotherapy, versus d. endocrine therapy + anti-HER2 targeted treatment + chemotherapy) in patients with a recurrence score (RS) < 26. The second model explores for differences in these systemic therapy approaches for those with a RS ≥ 26. Results: N=107,132 patients with early-stage, HR+/HER2+ breast cancer were included in this analysis. ODX testing was performed in n=5,280 (4.93%). The age distribution of this cohort was as follows: n=1,120 (21.2%) < 50 years, n=3,195 (60.5%) between 50-70 years, and n=965 (18.3%) were >70 years. The majority were White (84.9%), 9.6% were Black, and 3.3% were Asian. N=701 patients (13.3%) had a RS < 26, while n=4,353 (82.4%) had a RS >=26. The first Kaplan-Meier survival model indicated no significant difference in OS (p=0.445) between patients receiving different systemic treatment regimens when patients had a low risk of recurrence. However, the second Kaplan-Meier model indicates that when the ODX RS was ≥ 26, there was a statistically-significant difference in OS between systemic treatment regimens (p<0.001). 5-year OS was highest (97.4%) for patients receiving triple therapy (anti-HER2 + chemotherapy + endocrine therapy), followed by those receiving dual therapy with endocrine + anti-HER2 (96.7%), and endocrine + chemotherapy (94.9%). Patients receiving endocrine therapy alone exhibited the lowest 5-year OS (88.5%). Conclusion: Results from this large national cancer registry suggest that multi-gene testing with ODX may have predictive value in treatment selection of patients with early-stage, HR+/HER2+ breast cancer. Prospective trials are warranted to identify subgroups of patients with HR+/HER2+ breast cancer who can be spared anti-HER2 treatments and cytotoxic chemotherapy.

Citation Format: Nadeem Bilani, Marita Yaghi, Diana Saravia, Iktej Jabbal, Maroun Bou Zerdan, Leah Elson, Hong Liang, Zeina Nahleh. Does OncotypeDX have predictive value in HER2+ breast cancer? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-07.