De-escalating therapy dilemma in small HER2 positive node negative breast cancer.

Abstract

e12626 Background: Neoadjuvant therapy (NAT) is the standard of care for locally advanced HER2 positive breast cancer (BC) and provides pathologic complete response (pCR), a key prognostic factor and indicator to decide whether to escalate to adjuvant T-DM1 in case of residual disease, as per the KRISTINE trial. However, optimal sequencing of treatment (NAT vs. surgery first) is less clear in T1cN0 (stage I) HER2 positive BC. Moreover, the long-term follow-up of the Adjuvant Paclitaxel and Trastuzumab (APT) trial showed that deescalating chemotherapy is a possible strategy for small HER2-positive node negative breast cancers when tumor size is 3 cm or less. In clinical practice, there is a recurrent debate in multidisciplinary boards to decide the adequate strategy in small HER2 positive node negative BC. Although these tumors are considered of good prognosis, recent results by An et al. 2022 fuels the debate. They showed in a large observational cohort that T1N0 HER2 positive BC APT eligible treated with NAT and not achieving pCR have similar survival to patients with T2N0 tumors with residual disease, suggesting a higher risk group among small tumors.The aim of the study was to analyze the profile and outcome of APT eligible patients treated with NAT using a detailed tumor size breakdown. Methods: APT eligible patients treated with NAT were identified among a real-world cohort of 340 early HER2 positive BC patients receiving NAT at Oscar Lambret Cancer Center (Lille, France). The outcome of the APT eligible patients (n = 115) was analyzed according to tumor size ( < 15mm, 15-20mm, 21-30mm). Results: All patients were female with a median age of 54 years and received neoadjuvant anthracyclines followed by taxanes and trastuzumab. The ratio of hormone receptor (HR) positive / HR negative tumors was 72% / 28%. A similar distribution of grade 2 / grade 3 tumors was observed. Up to 75% of the patients did not have a complete pathologic response to NAT. In HR positive, the pCR rate was 43% in HER2 positive tumor of less than 15mm, 26% in tumors of 15-20mm, 25% in tumors of 21-30mm, and 32% in tumors of 31-50mm. In HR negative tumors, pCR rate was 81% in tumors of 15-20mm, 56% in tumors of 21-30mm, and 67% in tumors of 31-50mm. Conclusions: These results showed that APT eligible small HER2 positive and HR positive tumors had low chemosensitivity leading to adjuvant treatment escalation as per standard of care. It raises questions about the appropriate selection of patients for de-escalation in this population subset.