The Role of Trastuzumab in Patients with HER2 Positive Small (pT1mi/a) Breast Cancers, a Multicenter Retrospective Study

SIMPLE SUMMARY: Treatment of small HER2+ breast cancers with adjuvant Trastuzumab is still controversial. This study aims to measure the effect of Trastuzumab in early stages of breast cancer (pT1mic/a pN0/1mi) in terms of disease recurrence and to identify which factors most affect the prognosis of small HER2+ tumors. We retrospectively selected and reviewed 100 HER2+ pT1mic-pT1a breast cancer patients with a median follow-up of 86 months. In our study the primary outcome was the disease recurrence rate, which appeared to be significantly lower among patients who received adjuvant Trastuzumab. Among the patients who did not receive adjuvant Trastuzumab, HR− HER2+ tumors showed a risk seven times higher of relapse. The results of our study indicate that adjuvant Trastuzumab reduces the risk of developing a disease recurrence even in small HER2+ tumors. Adjuvant targeted therapy should be considered in patients with HR− HER2+ tumors, the category with the highest risk of recurrence. ABSTRACT: The treatment with adjuvant Trastuzumab in patients diagnosed with HER2+ small breast cancers is controversial: limited prospective data from randomized trials is available. This study aims to measure the effect of Trastuzumab in the early stages of breast cancer (pT1mic/a pN0/1mi) in terms of disease recurrence and to identify which are the factors that most affect the prognosis of small HER2+ tumors. One hundred HER2+ pT1mic-pT1a breast cancer patients who were treated in three Turin Breast Units between January 1998 and December 2018 were retrospectively selected and reviewed. Trastuzumab was administered to 23 patients. Clinicopathological features and disease-free survival (DFS) were compared between different subgroups. The primary outcome was the disease recurrence rate. Median follow-up time was 86 months. Compared to pT1a tumors, pT1mic lesions had a higher tumor grade (84% of pT1mic vs. 55% of pT1a; p = 0.003), a higher Ki-67 index (81% vs. 46%; p = 0.007) and were more frequently hormone receptor (HR) negative (69% vs. 36%, p = 0.001). Disease recurrence rate was significantly lower among patients who received adjuvant Trastuzumab (p = 0.02), with this therapy conferring an 85% reduction in the risk of relapse (HR 0.15; p = 0.02). Among the patients who did not receive adjuvant Trastuzumab, the only factor significantly associated with an increased risk of developing a recurrence was the immunohistochemical (IHC) subtype: in fact, HR− HER2+ tumors showed a risk seven times higher of relapsing (HR 7.29; p = 0.003). Adjuvant Trastuzumab appears to reduce the risk of disease recurrence even in small HER2+ tumors. The adjuvant targeted therapy should be considered in patients with HR− HER2+ tumors since they have the highest risk of recurrence, independently from size and grade.