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

Background Adjuvant pertuzumab improves the survival of patients with HER2-positive and node positive breast cancer. We aimed to evaluate the incidence and prognosis of patients eligible for adjuvant pertuzumab, both following primary resection and neoadjuvant therapy, during the modern era of preoperative treatment. 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-positive and node positive breast cancer were included in an adjuvant cohort comprising patients who underwent primary surgery, and a neoadjuvant cohort consisting of patients diagnosed with cN+ disease who received neoadjuvant therapy and achieved pathologic complete response (pCR). Median follow-up was 8.2 years (interquartile range, 4.4 – 12.0). Results Of 135080 patients diagnosed with breast cancer during the study period, 3495 were included into the adjuvant cohort. The proportion of patients eligible for adjuvant pertuzumab declined over the years. Ten-year overall survival in the adjuvant cohort was 71.6% (95% Confidence Interval [CI] 69.9 – 73.3%). Tumor size and nodal stage were independently prognostic, while estrogen receptor status was associated with late recurrence (time-dependent HR adj =1.96, 95% CI 1.21-3.19). Patients in the neoadjuvant cohort had excellent outcomes. Conclusions Although the proportion of patients with HER2-positive and node positive breast cancer who undergo primary surgery is decreasing, their poor long-term outcomes level underscore the relevance of adjuvant pertuzumab. In contrast, the recommendation for adjuvant pertuzumab to patients that achieve pCR should be revisited considering their excellent prognosis and likely marginal absolute benefit.