Efficacy of dose-dense (DD) adjuvant chemotherapy (CT) in hormone receptor positive/HER2-negative early breast cancer (BC) patients (pts) according to immunohistochemically (IHC) defined luminal subtypes: An exploratory analysis of the GIM2 trial

Background: DD adjuvant CT improves disease free survival (DFS) and overall survival (OS) in high-risk, hormone receptor positive BC. Luminal A and luminal B subtypes have different sensitivity to (neo)adjuvant chemotherapy; however, their role in predicting DD efficacy in clinically high-risk setting is uncertain. This exploratory analysis of the GIM2 trial (Del Mastro et al, Lancet 2015) evaluated DD efficacy according to IHC defined luminal subtypes. Methods: In the GIM2 trial, pts with node-positive early BC were randomized to receive 4 cycles of (fluorouracil) epirubicin/cyclophosphamide every 2 (DD) or every 3 (standard interval [SI]) weeks followed by 4 cycles of DD or SI paclitaxel. Luminal A-like and luminal B-like BC were identified according to 13h St Gallen definition as having a Ki67<20% and a PgR>/=20% (luminal A-like), and a Ki67>/=20% and/or a PgR<20% (luminal B-like). Pts with HER2-positive BC were excluded. The efficacy of DD CT in terms of DFS and OS was compared between the two subtypes. Results: Of 2,003 pts enrolled in the GIM2 trial, 401 had luminal A-like and 657 luminal B-like BC. After a median follow-up of 8 years, DFS was 81.1% (95% Confidence Intervals [CI] 76.6-84.7) and 70.6% (66.6-74.1) in luminal A-like and B-like BC, respectively; OS was 91.6% (88.1-94.1) and 85% (81.7-87.7), respectively. There was no significant interaction between treatment and luminal subtypes (pinteraction=0.416 for DFS and pinteraction=0.313 for OS); however, the effect of DD CT appeared to be greater in luminal-B like BC (see table below). [Table presented] Conclusions: These long-term results confirm the prognostic value of IHC-defined luminal subtypes, with luminal B-like bearing a worse prognosis. In clinically high-risk, hormone receptor positive BC, luminal B-like subtype benefits more from DD CT both in terms of DFS and OS. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: M. Lambertini: Honoraria (self), speaker honoraria: Theramex; Advisory / Consultancy: Teva. M. De Laurentiis: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Celgene. S. De Placido: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Eisai; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): Eli Lilly. F. Montemurro: Honoraria (self), speaker honoraria: AstraZeneca; Honoraria (self), speaker honoraria: Pfizer; Honoraria (self), speaker honoraria: Novartis; Honoraria (self), speaker honoraria: Eli Lilly; Honoraria (self), Travel / Accommodation / Expenses, speaker honoraria, travel grant: Roche. L. Del Mastro: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Ipsen; Honoraria (self): Roche-Genentech; Honoraria (self): Takeda; Honoraria (self): Eli Lilly. All other authors have declared no conflicts of interest.