Tumor biology or adjuvant systemic therapy: what determines the risk of recurrence in breast cancer stage I?

Aim: to study the prognostic value of clinical and morphological factors for the risk of recurrences in breast cancer stage I.Materials and methods: In study included 1341 women with breast cancer stage I (T1a-b-cN0M0), treated in the RCRC and RMAPE 1985-2012. We analyzed the clinical factors (age, volume of surgery, radiotherapy, type of adjuvant systemic therapy) and morphological factors (status of estrogen and progesterone receptors, HER2-status, proliferation activity index Ki-67, biological subtype, presence of lymph vascular invasion and intraductal component and the tumor size T1a-b-c). We assessed the risk of recurrence (median follow up - 96 months), the rate of relapse and disease-free survival in different subgroups using univariate and multivariate COX-regression analysis. Results: In univariate COX-regression analysis we found the prognostic value for the risk of recurrences of such morphological factors: grade of tumor ( p =0,034), histological type ( p =0,025), tumor size T1a-b-c ( p =0,004), presence of lymph vascular invasion ( p =0,03) and biological subtype of breast cancer ( p =0,002). The most favorable is the luminal A subtype with minimal rate of distant relapses (1,6%), the maximum time to progression (median - 48 months) and the best rate of the 5- and 10-year disease-free survival (97,2 and 93,8% respectively). The most important clinical factors were age ( p =0,001), the volume of surgery ( p =0,032), the using of «boost» after breast conservingtherapy ( p =0,007), and presence of adjuvant systemic therapy (chemotherapy, endocrine therapy or both therapy in accordance with the biological subtype, p <0,0001). In multivariate regression analysis, only two factors were significant for predicting the risk of recurrence of breast cancer stage I ( p <0,05): biological subtype and adjuvant systemic treatment. Compared with luminal A subtype the risk of relapse is significant higher in luminal B subtypes (HER2-negative: HR 1,393; HER2-positive: HR 1,321), in triple negative subtype - HR 2,297 and, especially, in hormone negative HER2-positive breast cancer - HR 6,001, p =0,04. Adjuvant systemic therapy reduce the risk of recurrence until 74% in breast cancer stage I (HR 0,276; p <0,0001).Conclusion: The tumor biology and adjuvant systemic therapy determines prognosis in breast cancer stage I.