Benedetta Conte1, Marco Bruzzone2, Matteo Lambertini3, Francesca Poggio4, Claudia Bighin4, Eva Blondeaux4, Michelino De Laurentiis5, Enrichetta Valle6, Francesco Cognetti7, Cecilia Nisticò8, Sabino De Placido9, Ornella Garrone10, Teresa Gamucci11, Filippo Montemurro12, Fabio Puglisi13, Barbara Cardinali14, Piero Fregatti15, Loredana Miglietta4, Francesco Boccardo3, Marcello Ceppi2, Lucia Del Mastro16. 1. Medical Oncology Unit 2, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, GE, Italy; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Carrer de Rosselló, 149, 08036, Barcelona, Spain. 2. Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, GE, Italy. 3. Medical Oncology Department, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 1632, Genoa, GE, Italy; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Viale Benedetto XV, 10, 16132, Genoa, GE, Italy. 4. Medical Oncology Unit 2, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, GE, Italy. 5. Breast Unit, Istituto Nazionale Tumori-Fondazione "G. Pascale", Via Mariano Semmola, 53, 80131, Naples, NA, Italy. 6. Department of Medical Oncology, Ospedale Businco, Via Edward Jenner, 1, 09121, Cagliari, CA, Italy. 7. Department of Clinical and Molecolar Medicine, La Sapienza University, Viale Regina Elena, 324, 00161, Rome, RM, Italy. 8. Department of Medical Oncology 1, Istituto Nazionale Tumori "Regina Elena", Via Elio Chianesi, 53, 00128, Rome, RM, Italy. 9. Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Sergio Pansini, 5, 80131, Naples, NA, Italy. 10. Breast Unit, Department of Oncology, Azienda Ospedaliera Santa Croce e Carle, Via Michele Coppino, 26, 12100, Cuneo, CN, Italy. 11. Department of Medical Oncology, Ospedale Sandro Pertini, Via dei Monti Tiburtini, 385/389, 00157, Rome, RM, Italy; Department of Medical Oncology, Ospedale SS Trinità, Località San Marciano, 03039, Sora, FR, Italy. 12. Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale, 142, 10060, Turin, TO, Italy. 13. Department of Medicine, University of Udine, Piazzale Massimiliano Kolbe, 4, 33100, Udine, Italy; Department of Medical Oncology, IRCCS Centro di Riferimento Oncologico Aviano - National Cancer Institute, Via Franco Gallini, 2, 33081, Aviano, PN, Italy. 14. Breast Unit, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, GE, Italy. 15. Department of Surgical Sciences and Integrated Diagnostic (DISC), University of Genova, Viale Benedetto XV, 6, 1612, Genoa, GE, Italy; Department of Surgery, IRCCS Policlinico San Martino, Largo Rosanna Benzi 10, 1632, Genoa, GE, Italy. 16. Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Viale Benedetto XV, 10, 16132, Genoa, GE, Italy; Breast Unit, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, GE, Italy. Electronic address: lucia.delmastro@hsanmartino.it.
Abstract
BACKGROUND: Luminal A-like and luminal B-like subtypes have different sensitivity to (neo)adjuvant chemotherapy, but their role in predicting dose-dense (DD) efficacy in the high-risk setting is unknown. In this exploratory analysis of the Gruppo Italiano Mammella 2 (GIM2) trial, we investigated DD efficacy according to luminal-like subtypes. METHODS:Patients with node-positive early breast cancer were randomised to receive either DD or standard-interval (SI) anthracycline-based chemotherapy followed by paclitaxel. In our analysis, luminal A-like cohort was identified as having a Ki67 < 20% and a progesterone receptor (PgR) ≥ 20%; luminal B-like cohort as having a Ki67 ≥ 20% and/or a PgR < 20%. RESULTS: Out of 2003 patients enrolled in the GIM2 trial, 412 had luminal A-like and 638 luminal B-like breast cancer. After a median follow-up of 7.9 years, disease-free survival (DFS) was 80.8% (95% confidence interval [CI] 76.4-84.5) and 70.5% (66.5-74.2) in luminal A-like and luminal B-like cohorts; overall survival (OS) was 91.6% (88.2-94.1) and 85.1% (81.7-87.9), respectively. We found no significant interaction between treatment and luminal subtype (interaction p = 0.603 and 0.535 for DFS and OS, respectively). When DD efficacy was investigated separately in each cohort, luminal-B like cohort appeared to benefit more from the DD schedule both in terms of DFS (unadjusted hazard ratio [HR] 0.72 [95% CI 0.54-0.96]) and OS (unadjusted HR 0.61 [95% CI 0.40-0.94]), compared with the luminal A-like cohort (unadjusted HR for DFS 0.89 [95% CI 0.59-1.33]; unadjusted HR for OS 0.83 [95% CI 0.45-1.54]). CONCLUSIONS: No significant interaction between luminal-like subtype and treatment was observed. Patients in the luminal B-like cohort seemed to benefit more from DD schedule.
RCT Entities:
BACKGROUND:Luminal A-like and luminal B-like subtypes have different sensitivity to (neo)adjuvant chemotherapy, but their role in predicting dose-dense (DD) efficacy in the high-risk setting is unknown. In this exploratory analysis of the Gruppo Italiano Mammella 2 (GIM2) trial, we investigated DD efficacy according to luminal-like subtypes. METHODS:Patients with node-positive early breast cancer were randomised to receive either DD or standard-interval (SI) anthracycline-based chemotherapy followed by paclitaxel. In our analysis, luminal A-like cohort was identified as having a Ki67 < 20% and a progesterone receptor (PgR) ≥ 20%; luminal B-like cohort as having a Ki67 ≥ 20% and/or a PgR < 20%. RESULTS: Out of 2003 patients enrolled in the GIM2 trial, 412 had luminal A-like and 638 luminal B-like breast cancer. After a median follow-up of 7.9 years, disease-free survival (DFS) was 80.8% (95% confidence interval [CI] 76.4-84.5) and 70.5% (66.5-74.2) in luminal A-like and luminal B-like cohorts; overall survival (OS) was 91.6% (88.2-94.1) and 85.1% (81.7-87.9), respectively. We found no significant interaction between treatment and luminal subtype (interaction p = 0.603 and 0.535 for DFS and OS, respectively). When DD efficacy was investigated separately in each cohort, luminal-B like cohort appeared to benefit more from the DD schedule both in terms of DFS (unadjusted hazard ratio [HR] 0.72 [95% CI 0.54-0.96]) and OS (unadjusted HR 0.61 [95% CI 0.40-0.94]), compared with the luminal A-like cohort (unadjusted HR for DFS 0.89 [95% CI 0.59-1.33]; unadjusted HR for OS 0.83 [95% CI 0.45-1.54]). CONCLUSIONS: No significant interaction between luminal-like subtype and treatment was observed. Patients in the luminal B-like cohort seemed to benefit more from DD schedule.