Journal Article

Treatment Outcomes of HER2-Directed Therapy in Patients With HER2-Positive Non-metastatic Breast Cancer in Low-Resource Settings

Shahzad, Minahil, Karim, Amna, Imran, Maryam, Majeed, Muhammad Awais, Akhtar, Fatima, Bano, Shehar, Abdullah Javaid Bukhari, Syed, Aqib, Beenish, Jamil, Muhammad Ahsan, Bin Naeem, Sameen, Ahmad, Aftab

2025

Overview

Introduction This study aimed to evaluate treatment outcomes of human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with non-metastatic HER2-positive breast cancer treated in a low-resource setting. Specifically, we assessed the impact of dual blockade (trastuzumab and pertuzumab), trastuzumab alone, or no HER2-targeted therapy on rates of residual disease, pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Methods We conducted a retrospective cohort study at Shaukat Khanum Memorial Cancer Hospital, including 299 patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant chemotherapy and either dual HER2 blockade, trastuzumab alone, or no HER2-targeted therapy due to financial constraints. Patient demographics, clinical features, treatments, and outcomes were analyzed using descriptive statistics, chi-square tests, and Kaplan-Meier survival analysis. Results The median age at diagnosis was 45.7 years (standard deviation±8.9). A majority of patients were premenopausal (n=222; 74.2%), and the majority presented with a palpable lump (n=275; 91.9%). Tumors were mainly located in the left (n=149; 49.8%) or right breast (n=147; 49.2%), with bilateral involvement in 3 (1.0%) cases. Invasive ductal carcinoma was the predominant histology (n=275; 91.9%), with estrogen receptor and progesterone receptor positivity observed in 185 (61.9%) and 179 (59.9%) patients, respectively. Grade III tumors were observed in 156 (52.2%) cases, and most tumors were T2 stage (n=236; 78.9%) with axillary nodal involvement in 232 (77.6%). Patients receiving dual HER2 blockade achieved a pCR in 45 (54.9%) of 82 cases, compared to 51 (45.9%) of 111 with trastuzumab alone, and 39 (36.8%) of 106 with no HER2 therapy (p=0.046). The docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen had the highest pCR rate in 19 (65.5%) of 29 patients (p<0.001). Grade III tumors were associated with higher pCR than Grade II (n=96; 56.5% vs. n=39; 30.2%; p<0.001). At 60 months, PFS was 236 (79.0%) overall, highest in the dual blockade group (n=73; 89.0%), followed by trastuzumab (n=96; 86.5%) and no HER2 therapy (n=69; 65.1%). OS at 60 months was 271 (90.6%), highest in the dual blockade group (n=78; 95.1%), then trastuzumab (n=102; 91.9%) and no HER2 therapy (n=79; 74.5%). Achieving pCR was associated with improved PFS and OS. Differences in both outcomes across groups were statistically significant (p<0.001). Conclusion Dual HER2 blockade significantly improved pCR, PFS, and OS in non-metastatic HER2-positive breast cancer. These findings support the inclusion of HER2-targeted agents in standard neoadjuvant treatment, even in resource-limited settings. Addressing barriers to access remains essential to improving global outcomes in breast cancer care.

• Publisher: Cureus Inc
• Subject: Oncology