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

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.