Giulia Galli1, Giacomo Bregni2, Stefano Cavalieri1, Luca Porcu3, Paolo Baili4, Amash Hade4, Francesca Di Salvo4, Milena Sant4, Roberto Agresti5, Massimiliano Gennaro5, Secondo Folli5, Maria C De Santis6, Biagio Paolini7, Maria L Carcangiu7, Filippo de Braud1, Serena Di Cosimo8. 1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 2. Unit of Medical Oncology 1, IRCCS AOU San Martino-IST, Genova, Italy. 3. Computational Statistics Unit, Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. 4. Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 5. Department of General Surgery 3, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 6. Department of Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 7. Department of Pathology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 8. Dipartimento di Ricerca Applicata e Sviluppo Tecnologico (DRAST), Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Abstract
BACKGROUND: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. MATERIALS AND METHODS: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemar's test was used to compare paired proportions. RESULTS: Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation. CONCLUSIONS: The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.
BACKGROUND: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. MATERIALS AND METHODS: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemar's test was used to compare paired proportions. RESULTS: Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation. CONCLUSIONS: The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.
Entities:
Keywords:
Breast cancer; Chemotherapy, neoadjuvant; Endocrine therapy; Residual disease
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