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Background Standard treatment in early HER2 positive BC involves the use of neoadjuvant chemotherapy (NACT) with Trastuzumab (T) plus Pertuzumab (P). Dual blockade increases pathological complete response (pCR) and improves disease free survival (DFS). However, Chilean public health system does not include P use in the NACT schedule, while private insurers only provide partial coverage. Here, we aim to compare pCR, Distant DFS (DDFS) and site of recurrence in HER2 positive BC patients treated in the neoadjuvant setting with the use of T with or without P, in the largest BC Chilean registry. Methods We conducted a retrospective population-cohort study involving females with stage I-III HER2 positive BC treated with NACT in a public and academic private centre between 2012 to 2021. CT regimens for comparison included anthracyclines, taxanes, T and P. pCR was defined as the absence of residual invasive disease in the breast and in the axillary lymph nodes (ypT0/is N0) at the completion of the NACT. DDFS was measured from the time of diagnosis to the event or lost to follow-up. We performed Cox regression analysis to identify factors associated with prognosis and a logistic regression to identify factors related to the first metastasis site. Results 372 patients with HER2 positive BC were included. Median age was 51 years (24 – 79), 57.5% were classified as Hormone Receptor positive (HR), and 4.5% were stage I, 48.2% stage II and 47.3% stage III. 65.8% were treated in a Public Hospital (PH) and 34.2% in an Academic Private Centre (AC). 85.2% received both anthracyclines and taxanes, 10.0% only taxanes and 4.8% only anthracyclines-based CT. 55 patients (14.8%) received both T and P, while 3.3% did not receive any HER2 directed therapy as NA treatment. Median T doses before surgery were 6 (1 – 12). pCR rate was 46.5% which varied according to HR expression: 61.0% in HR-positive BC vs. 36.2% in HR-negative disease (p=0.0001). pCR according to treatment were as follows: no-T no-P 22.2%, only-T 49.4%, both T-P 60.0% (p=0.02). We found no difference in pCR rate between anthracycline and non-anthracycline based CT (49.1% vs. 45.9%, p=0.72). With a median follow-up of 36 months, DDFS at 3 and 5 years differed regarding pathological response: 94.8% vs. 77.1% and 86.3% vs. 69.1% (p=0.0006), for pCR and non-pCR group, respectively. In a multivariate analysis, stage III vs. I-II (HR 2.5, p=0.005), non-pCR vs. pCR (HR 2.6, p=0.01) and not receiving NA anti-HER2 treatment (HR 2.6, p=0.01) were associated with higher risk of distant metastasis. Regarding recurrence, 7 out of 198 non-pCR tumors and 6 out of 174 pCR tumors presented brain metastasis (BM) as the first site of distant recurrence(p=0.96). In contrast, visceral metastasis (VM) as the first site of recurrence, were more frequent in non-pCR (21/198) than pCR patients (3/174, p=0.001). In a multivariate analysis, the only factor associated with BM was stage III (HR 5.8 vs stage I-II, p=0.02) and with VM was not achieving pCR (HR 6.3, p=0.02) and not using T nor P (HR 5.1, p=0.008). Conclusion The use of anti-HER2 treatment in a NA scheme is critical in HER2 positive disease. Although P is associated with increased pCR, we found no survival benefit with its use. Retrospective analysis, few events, post-surgical treatment might have influenced these results. Achieving pCR is associated with better prognosis by reducing distant recurrence but not BM. New strategies are needed to prevent the occurrence of this event. Citation Format: FRANCISCO ACEVEDO, Benjamin Walbaum, Lidia Medina, Tomas Merino, Catherine Bauerle, Mauricio Camus, Augusto Leon, Manuel Manzor, Paulina Veglia, Raul Martinez, Constanza Guerra, Marisel Navarro, Francisco Dominguez, CÉSAR SÁNCHEZ. The real-world outcome of human epidermal growth factor type-2 positive breast cancer patients receiving neoadjuvant therapy with or without pertuzumab [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 P1-11-17. |
