Long-term survival of advanced triple- negative breast cancers with a dose-intense cyclophosphamide/anthracycline

AP-HP, Hoˆpital Saint-Louis, RadiologyDepartment, Paris 75475, FranceBackground: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally havea poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in thesecancers.Methods: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with twodifferent neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide–anthracycline (AC) association(historicallycalled SIM)oraconventional sequentialassociation ofcyclophosphamideandanthracycline,followed bytaxanes(EC-T).We compared pathological responses and survival rates of these two groups and studied their association with tumours features.Results: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P¼0.087) in TN tumours. In the SIMprotocol, DFS was statistically higher for TN than for non-TN patients (P¼0.019), although we showed that the TN status wasassociated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN wasassociated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)¼0.25 (95% CI: 0.07–0.86),P¼0.028).Conclusions: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers.These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours.Breast cancers represent a set of highly heterogeneous diseases(Weigelt et al, 2008; Sotiriou and Pusztai, 2009). Ongoing studies arepursuing the identification of the cell of origin as well as genetic andepigenetic changes or alterations in signalling pathways associatedwith each breast cancer subset. Currently, these molecularclassifications are not routinely used in clinical practice and breastcancers are still commonly classified according to oestrogen receptor(ER), progesterone receptor (PR) and HER2 status. However, triple-negative (TN) cancer is phenotypically defined by the lack ofexpression of ERA, PR and the absence of HER2 overexpression andamplification. There are not yet any specifically targeted treatmentsfor this type of breast cancer. Cytotoxic chemotherapy is therefore