Abstract
Simple SummaryTreatment 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.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.
Highlights
The implementation of mammographic screening during the last decades has led to changes in the size-specific distribution of breast cancer, with increased detection of small breast tumors
The present study aims at measuring the effect of Trastuzumab in very small early breast cancers in terms of disease recurrence, and at identifying the factors that most affect the prognosis of small human epidermal growth factor receptor 2 (HER2)+ tumors
Among patients with small HER2+ breast cancers, disease recurrence rate was significantly lower among patients who received adjuvant Trastuzumab (4% Trastuzumab group vs. 26% non-Trastuzumab group, p = 0.02), with this therapy conferring an 85% reduction in the risk of relapse (HR 0.15; 95%confidence intervals (CI) 0.10–0.97; p-value: 0.048)
Summary
The implementation of mammographic screening during the last decades has led to changes in the size-specific distribution of breast cancer, with increased detection of small breast tumors. The American Joint Committee on Cancer Staging Manual lists “T1mic” in the TNM classification and defines microinvasion as the extension of cancer cells beyond the basement membrane into the adjacent tissue with focus up to 1 mm in the greatest dimension. Invasive components exceeding this size are classified as T1a if the diameter ranges from 2 to 5 mm [2]. Factors found to be associated with poorer outcomes are high tumor grade, hormone receptors (HR) negative status, young age at diagnosis, high Ki-67 values, lympho-vascular invasion, and human epidermal growth factor receptor 2 (HER2) expression [4,5,6]
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