Carmen Criscitiello1, Davide Disalvatore2, Michele De Laurentiis3, Lucia Gelao1, Luca Fumagalli1, Marzia Locatelli1, Vincenzo Bagnardi4, Nicole Rotmensz2, Angela Esposito1, Ida Minchella1, Sabino De Placido5, Michele Santangelo6, Giuseppe Viale7, Aron Goldhirsch1, Giuseppe Curigliano8. 1. Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy. 2. Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. 3. Department of Breast Oncology, National Cancer Institute "Fondazione Pascale", Naples, Italy. 4. Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy; Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy. 5. Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Napoli, Italy. 6. Department of Advanced Medical Sciences, Operative Unit of General Surgery and Transplants, University of Naples Federico II, Napoli, Italy. 7. Division of Pathology, European Institute of Oncology, Milan, Italy; University of Milan School of Medicine, Milan, Italy. 8. Early Drug Development for Innovative Therapies Division, Department of Medicine, European Institute of Oncology, Milan, Italy. Electronic address: giuseppe.curigliano@ieo.it.
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. PATIENTS AND 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.
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. PATIENTS AND 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.
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