Effect of dose-dense adjuvant chemotherapy in hormone receptor positive/HER2-negative early breast cancer patients according to immunohistochemically defined luminal subtype: an exploratory analysis of the GIM2 trial: European Journal of Cancer

B. Conte, M. Bruzzone, M. Lambertini, F. Poggio, C. Bighin, E. Blondeaux, M. De Laurentiis, E. Valle, F. Cognetti, C. Nisticò, S. De Placido, O. Garrone, T. Gamucci, F. Montemurro, F. Puglisi, B. Cardinali, P. Fregatti, L. Miglietta, F. Boccardo, M. CeppiL. Del Mastro, the GIM2 Investigators

Research output: Contribution to journalArticlepeer-review

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. © 2020 Elsevier Ltd
Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalEur. J. Cancer
Volume136
DOIs
Publication statusPublished - 2020

Keywords

  • Breast cancer
  • Dose-dense chemotherapy
  • Hormone receptor-positive
  • Luminal subtype
  • cyclophosphamide
  • epirubicin
  • fluorouracil
  • Ki 67 antigen
  • paclitaxel
  • pegfilgrastim
  • progesterone receptor
  • antineoplastic agent
  • epidermal growth factor receptor 2
  • estrogen receptor
  • adjuvant therapy
  • adult
  • age
  • aged
  • Article
  • cancer adjuvant therapy
  • cancer free survival
  • cancer grading
  • cancer recurrence
  • controlled study
  • disease free survival
  • dosage schedule comparison
  • dose densification
  • early cancer
  • female
  • follow up
  • human
  • human epidermal growth factor receptor 2 negative breast cancer
  • human epidermal growth factor receptor 2 positive breast cancer
  • immunohistochemistry
  • luminal A breast cancer
  • luminal B breast cancer
  • major clinical study
  • multiple cycle treatment
  • overall survival
  • priority journal
  • randomized controlled trial
  • recurrence risk
  • adjuvant chemotherapy
  • breast tumor
  • cancer staging
  • clinical trial
  • cohort analysis
  • disease exacerbation
  • dose response
  • metabolism
  • middle aged
  • mortality
  • multicenter study
  • pathology
  • phase 3 clinical trial
  • phenotype
  • prognosis
  • survival analysis
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Phenotype
  • Prognosis
  • Receptor, ErbB-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Survival Analysis

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