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Abstract Background: Breast Cancer is the most diagnosed cancer type worldwide and the second leading cause of cancer-related death among women. HER2-low breast cancer is a newly defined molecular subtype of breast cancer in which tumors exhibit a minimal overexpression of HER2 or no gene amplification. To illustrate, HER2-low tumors typically have an IHC score of 1+ or a score of 2+ with negative amplification. However, emerging evidence suggests that even a minimal amplification of HER2 may significantly impact the response to therapy and prognosis. Our study aims to unveil the impact of HER2-low expression on the response to anthracycline and taxane-based neoadjuvant chemotherapy (NACT) in comparison to the HER2-negative group in non-metastatic breast cancer. The primary objective was evaluating the response to NACT comparing the favorable response (complete and partial response) in each of the two groups of HER2-low and HER2-negative patients. Methods: This is a retrospective cohort study. All patients’ profiles with non-metastatic, HER2-Low, and HER2-negative breast cancers who received neo-adjuvant chemotherapy and underwent surgery between the 1st of January 2018 and the 30th of August 2022 were included. Patients' response was evaluated using surgical pathology reports to compare the two study groups (HER2-low and HER2-negative). Results: The total number of patients included was 262 patients, the majority were HER2-low 89% (233/262) vs. 11% (29/262) HER2-negative. A favorable response to NACT was shown in 71% (185/262) of all patients. The favorable response rate was similar in both groups, 70% (164/233) in the HER2-low group vs. 72% (21/29) in the HER2-negative group, OR: 1 (95% CI: 0.8-1), p-value 0.8. Similarly, the pathological complete response (pCR) rate was the same in both study groups at 14%, OR: 0.7 (95% CI: 0.2-3), p-value: 0.6. Interestingly, patients with hormone-positive tumors across both study groups had a higher response rate as compared to hormone-negative patients. However, statistical significance was shown in the HER2-low group only. In the HER2-low cohort, 73% of the patients (119/164) with hormone-positive tumors showed a favorable response OR: 0.8 (95% CI: 0.8- 1), p-value: 0.001. Comparatively, in the HER2-negative cohort, 52% of the patients (11/21) with hormone-positive tumors had a favorable response OR: 2 (95% CI: 1– 5), p-value: 0.05. Conclusion: Our results did not show any significant impact of HER2-low expression on neoadjuvant chemotherapy response. Nonetheless, a statistically significant difference in response was observed in the hormone-positive HER2-low breast cancer patients. Further studies are needed to evaluate the influence of hormonal expression on the response rate to NACT in the HER2-low patient population. Citation Format: Ahmed Kardousha, Wafaa Shehada, Ahmed Basha, Sahar Nasser, Mufid el Mistiri, Anas Hamad, Salha Al-Bader, Shereen Elazzazy. HER2 Low Non-Metastatic Breast Cancer in Qatar: A Nationwide Retrospective Cohort Study to Evaluate the Response to Neoadjuvant Chemotherapy: A Real-World Analysis 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 PO1-02-07.
Kardousha et al. (Thu,) studied this question.