Prognostic Role of Nodal Status and Clinically Asymptomatic Valvular Insufficiency in Patients with HER2-positive Breast Cancer Treated with Chemotherapy, Radiotherapy and Trastuzumab in an Adjuvant Setting.

Aim: The aim of the present study was to assess metastasis-free survival of 134 patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with chemotherapy, radiotherapy and trastuzumab in an adjuvant setting, according to sub-clinical cardiac side- effects (parameters not tested previously) evaluated before, during and after trastuzumab therapy, as well as selected clinicopathological parameters. Results: In our series, left ventricular ejection fraction decreased significantly from 68.1% before trastuzumab treatment to 66.7% after therapy (p<0.001). Further analysis revealed that this decrease was significant only in patients who received radiotherapy and developed valve insufficiency during or after (but not before) trastuzumab therapy (p<0.001). Cox multivariate analysis revealed that both pN2a tumor stage and valve regurgitation during/after trastuzumab therapy (vs. lack of valve insufficiency or insufficiency before trastuzumab therapy) were significant independent factors for a negative prognosis. Conclusion: Valve insufficiency diagnosed during or after trastuzumab application might be cancer-unrelated indicator of decreased sensitivity to trasuzumab. In the absence of trastuzumab therapy, patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer present poorer disease-free and overall survival compared to HER2-negative ones. Clinical trials revealed that the addition of trastuzumab to standard chemotherapy was associated with a decreased risk of breast cancer progression and cancer-related deaths (1). Despite optimistic results, treatment schedules applied for HER2-positive breast cancer are associated with increased cardiovascular co- morbidities (1, 2).