title: High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in luminal B HER2 negative and node-positive breast cancer.
abstract: BACKGROUND
  The indication of adjuvant chemotherapy for patients with highly proliferative estrogen receptor-positive breast cancer is controversial. We analyzed the predictive value of Ki67 for the efficacy of adjuvant chemotherapy in patients with estrogen receptor-positive, node-positive breast cancer.
  
  
  METHODS
  We identified 1241 patients with Luminal B early stage breast cancer with 1-3 axillary positive nodes who underwent surgery between 1995 and 2005 at the European Institute of Oncology and received adjuvant hormonotherapy and/or chemotherapy. Differences in the distribution of characteristics according to treatment were evaluated by the Chi-square test. To evaluate the effect of adding chemotherapy to hormonotherapy, the propensity score method was used to match patients' characteristics minimizing bias related to the non-random assignment of treatment.
  
  
  RESULTS
  The probability of receiving chemotherapy was significantly associated with age, tumor grade, degree of hormone responsiveness, tumor size and peripheral vascular invasion. The propensity score distribution was statistically different between the two treatment groups (p < 0.0001). The 5-year OS percentages were 95.8% (95% CI, 93.5-97.2) in the hormonotherapy group and 96.2% (95%CI, 94.4-97.4%) in the hormonotherapy/chemotherapy group (log-rank test p-value 0.663). The 5-year DFS percentages were 84.6% (95% CI, 81.0-87.6%) in the hormonotherapy group and 84.2% (95% CI, 81.3-86.7%) in the hormonotherapy/chemotherapy group (log-rank test p-value 0.388). However, when analyzing the 5-year DFS by Ki-67 distribution, Subpopulation Treatment Effect Pattern Plot (STEPP) analysis showed a beneficial effect of chemotherapy in patients with highly proliferative tumor (Ki-67 ≥ 32%). The interaction between Ki-67 and treatment was statistically significant (p = 0.027).
  
  
  CONCLUSIONS
  Ki67 expression identifies a subset of patients with Luminal B and node-positive breast cancer who could benefit from addition of adjuvant chemotherapy to hormonotherapy. Dichotomy was observed for Ki67 at 32% level.
authors: Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors: Carmen
authors: C
authors: Criscitiello
authors: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors: Davide
authors: D
authors: Disalvatore
authors: Department of Breast Oncology, National Cancer Institute "Fondazione Pascale", Naples, Italy.
authors: Michele
authors: M
authors: De Laurentiis
authors: Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors: Lucia
authors: L
authors: Gelao
authors: Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors: Luca
authors: L
authors: Fumagalli
authors: Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors: Marzia
authors: M
authors: Locatelli
authors: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy; Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
authors: Vincenzo
authors: V
authors: Bagnardi
authors: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors: Nicole
authors: N
authors: Rotmensz
authors: Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors: Angela
authors: A
authors: Esposito
authors: Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors: Ida
authors: I
authors: Minchella
authors: Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Napoli, Italy.
authors: Sabino
authors: S
authors: De Placido
authors: Department of Advanced Medical Sciences, Operative Unit of General Surgery and Transplants, University of Naples Federico II, Napoli, Italy.
authors: Michele
authors: M
authors: Santangelo
authors: Division of Pathology, European Institute of Oncology, Milan, Italy; University of Milan School of Medicine, Milan, Italy.
authors: Giuseppe
authors: G
authors: Viale
authors: Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors: Aron
authors: A
authors: Goldhirsch
authors: Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy. Electronic address: giuseppe.curigliano@ieo.it.
authors: Giuseppe
authors: G
authors: Curigliano
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: Breast cancer; Chemotherapy; Hormonotherapy; Ki67; Luminal B; Nodal involvement