Abstract PS5-04-09: Pathological complete response rates, treatment patterns, and survival outcomes in high risk, neoadjuvant-treated HER2-positive early breast cancer: a Canadian chart review

Abstract Background: For patients with high risk HER2-positive (HER2+) early breast cancer (eBC), neoadjuvant therapy (NAT) aims to reduce recurrence and the need for treatment intensification. Patients typically undergo months of systemic therapy, which can be accompanied by toxicities, followed by surgery. Post-operative recovery may be complicated by surgical morbidity, and the need for further intensive adjuvant therapies can add to the burden. A pathological complete response (pCR) is regarded as a meaningful marker of therapeutic efficacy and is pivotal in the patient experience. However, real world evidence from Canada on treatment patterns, pCR rates, and key outcomes, including surgical type, complications, and subsequent adjuvant therapy, is limited for this population. Methods: We conducted a retrospective chart review of a random subset of adults (≥18 years) with non-metastatic, high risk (T0-4N1-3M0 or T3-4N0M0) HER2+ eBC treated with NAT (chemotherapy with or without anti-HER2 agents) at Alberta cancer centres between 2013 and 2022, identified from the Oncology Outcomes database, with follow up through August 2024. Primary objectives were to describe pCR rates and neoadjuvant and post-neoadjuvant treatment patterns. Secondary objectives included real world (rw) recurrence-free survival (rwRFS), event free survival (rwEFS), invasive disease free survival (rwiDFS), and overall survival (rwOS). Exploratory analyses examined associations between pCR and clinical factors with these outcomes. Descriptive statistics summarized baseline and treatment characteristics; time to event outcomes were analyzed with Kaplan Meier methods; associations with clinical factors were evaluated using Cox regression. Results: Among 606 patients (mean age 50.6 years; mean follow up 5.4 years), 65.2% (n=395) were hormone receptor (HR) positive, 34.8% (n=211) hormone receptor negative; 35.3% (n=214) received anthracycline containing NAT, 64.7% (n=392) non-anthracycline containing NAT; 95.0% (n=576) had >4 NAT cycles; 79.2% (n=480) received radiation therapy, 90.2% (n=433) within 12 weeks of surgery. Of 571 patients with known pCR status, 46.9% (n=268) achieved pCR. Breast conserving surgery was more common among those with pCR (53.3% [n=105]) vs without (46.7% [n=92]); mastectomy was more frequent among those without pCR (56.4% [n=211]) than with (43.6% [n=163]). Nodal dissection was less frequent in breast conserving surgery (27.4% [n=132]) vs mastectomy (72.6% [n=350]). Among 583 patients receiving adjuvant therapy, trastuzumab was most common (79.9% [n=484]), followed by trastuzumab emtansine (T-DM1, 11.9% [n=72]), pertuzumab + trastuzumab (2.8% [n=17]), and other therapies (1.7% [n=10]); T-DM1 was used almost exclusively in patients without pCR. At 5 years, patients with pCR had higher rwRFS (90.1% vs 80.8%), rwEFS (87.8% vs 78.2%), rwiDFS (87.3% vs 77.4%), and rwOS (91.3% vs 87.3%) compared to those without. In a Cox proportional hazards model (adjusted for age, HR status, immunohistochemistry, Charlson comorbidity index, institution type, NAT cycles), pCR was associated with reduced risk for all events (adjusted HR [95% confidence interval] for pCR vs non-pCR: rwRFS: 0.41 [0.26-0.66]; rwEFS: 0.46 [0.31-0.70]; rwiDFS: 0.44 [0.29-0.68]; rwOS: 0.52 [0.30-0.88]; all p<0.001). Conclusions: pCR following NAT is a key milestone for patients with high-risk HER2+ eBC, being associated with less intensive surgical management, a reduced need for further intensive adjuvant therapy, and improved survival outcomes. Overall rates of adjuvant T-DM1 use may reflect recency of public funding. Lower pCR rates, compared to clinical studies of HER2-based NATs, may reflect limited public funding for NAT pertuzumab in Canada during the study period. Citation Format: W. Y. Cheung, J.-W. Henning, S. Shokar, M. T. Warkentin, Z. Senhaji Mouhri, M. Badin, A. Nam. Pathological complete response rates, treatment patterns, and survival outcomes in high risk, neoadjuvant-treated HER2-positive early breast cancer: a Canadian chart review [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-04-09.