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Background: Neoadjuvant chemotherapy is the standard of care for early stage breast cancer. Human epidermal growth factor receptor 2 (HER2) positive disease constitutes a large proportion of breast cancer patients, and HER2 overexpression is associated with poor prognosis. The induction of HER2+ targeted therapies, such as trastuzumab and pertuzumab, has resulted in improved outcomes in HER2+ breast cancers. Neoadjuvant chemotherapy in combination with HER2 targeted therapies aims at achieving pathological complete response (pCR) and an improved survival. Methods: We performed a retrospective review of HER2+ breast cancer patients who were treated at Medanta – The Medicity Hospital, Gurugram, Haryana, India, between 2011 and 2021. A total of 108 HER2+ breast cancer patients who received neoadjuvant chemotherapy with platinum, anthracycline or taxane-based regimens, along with trastuzumab alone or in combination with pertuzumab, were included. Results: Of 108 enrolled patients, 66 and 42 patients received single-blockade (trastuzumab) and dual-blockade (trastuzumab and pertuzumab) neoadjuvant anti-HER2 therapy, respectively. The majority of patients were aged < 60 years. The patient populations were comparable in terms of clinical stage, hormone receptor status, histopathology category (IDC being most common) and Ki67 status for single- and dual-blockade groups. All patients had IHC3+/FISH+ HER2 expression. No significant (p=0.896) difference was observed for breast conserving surgery between the groups. A higher pCR rate after surgery was reported in the dual-blockade group versus single-blockade group (50% vs. 39.2%; p=0.271). The median follow-up duration was 21.9 and 15.2 months in the single-blockade and dual-blockade groups, respectively. For dual- vs. single- blockade groups, the 1-year OS rates were 100% vs. 100%, and 3-year OS rates were 100% vs. 98.48%. For dual- vs. single- blockade groups, the 1-year DFS rates were 100% vs. 95.45%, and 3-year DFS rates were 92.85% vs. 80.3%. Conclusion: Neoadjuvant chemotherapy with dual HER2-blockade had higher pCR and survival rates compared with the single HER2-blockade strategy in HER2 positive breast cancer. Table. Patient characteristics BCS, breast conserving surgery; ER, estrogen receptor; PR, progesterone receptor; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma. Citation Format: Ashok K. Vaid, Devender Sharma, Jyoti Wadhwa, Rajeev Agarwal, Kanchan Kaur, Shina Goyal, Dheeraj Gautam, Jyoti Arora, Sabhyata Gupta, Ashok Sen, Ruchika K. Goel, Shagun Mahajan. Real-World, Single-Center Experience on the Outcomes of Neoadjuvant Chemotherapy and Trastuzumab alone or in Combination with Pertuzumab in Human Epidermal Growth Factor Receptor 2 Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-62.