A nationwide population-based study on the incidence and prognosis of patients with HER2+ breast cancer eligible for adjuvant pertuzumab in the modern era of neoadjuvant therapy.

Abstract

e12508 Background: The addition of pertuzumab to adjuvant chemotherapy and trastuzumab improves overall survival (OS) of patients with HER2+ and node positive (N+) breast cancer. Adjuvant pertuzumab, while recommended by ESMO and NCCN for both primary resected pN+ and neoadjuvant treated cN+ breast cancer with pathologic complete response (pCR), is not used in Sweden due to concerns about its cost effectiveness. Here, we aimed to evaluate the relevance of the APHINITY trial during the era of neoadjuvant treatment and the prognosis of patients eligible for adjuvant pertuzumab. Methods: This was a retrospective analysis of a prospectively collected, nationwide, population-based cohort that comprises all patients treated for breast cancer in Sweden between 2007-2023. Patients with non-metastatic, HER2+ and N+ breast cancer were included into an adjuvant cohort comprising patients eligible for the APHINITY trial who underwent primary surgery and had pN1–3 disease, and a neoadjuvant cohort consisting of patients diagnosed with cN+ disease who received neoadjuvant trastuzumab-based therapy and achieved pCR. Median follow-up was 8.4 years (IQR, 4.6-12.0). Results: Of 135080 patients diagnosed with DCIS or invasive breast cancer (all stages) in Sweden during the study period, 3495 were included into the primary resected adjuvant cohort. The proportion of patients eligible for adjuvant pertuzumab declined over the years, in parallel with the increasing use of neoadjuvant treatment. 10-year OS in the adjuvant cohort was 71,6% (95% CI 69,9-73,3%). Tumor size and nodal stage were independently prognostic, while ER positivity was associated with late recurrence (time-dependent HR adj = 1.96, 95% CI 1.21-3.19 at 10 years). On the other hand, patients in the neoadjuvant cohort (n = 465) had excellent outcomes, with 10-year OS of 92,3% (95% CI 84,1-100%). Conclusions: Although the proportion of patients with HER2+ and N+ breast cancer that undergo primary surgery instead of neoadjuvant therapy is steadily decreasing, the poor long-term outcomes at the population level underscore the relevance of adjuvant pertuzumab. In contrast, the recommendation by NCCN and ESMO for adjuvant pertuzumab to patients with cN+ that achieve pCR should be revisited in light of their excellent prognosis and likely marginal absolute benefit with pertuzumab.