Tumor histological subtyping determined by hormone receptors and HER2 status defines different pathological complete response and outcome to dose-dense neoadjuvant chemotherapy in breast cancer patients

• Published in: Clinical & translational oncology Vol. 16; no. 6; pp. 548 - 554
• Main Authors: Sánchez-Muñoz, A., Plata-Fernández, Y., Fernández, M., Jaén-Morago, A., Fernández-Navarro, M., de la Torre-Cabrera, C., Ramirez-Tortosa, C., Pascual, J., Alba, E., Sánchez-Rovira, P.
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01.06.2014
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - mortality; Carcinoma, Ductal, Breast - pathology; Carcinoma, Lobular - metabolism; Carcinoma, Lobular - mortality; Carcinoma, Lobular - pathology; Chemotherapy, Adjuvant; Cyclophosphamide - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Doxorubicin - administration & dosage; Epirubicin - administration & dosage; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oncology; Paclitaxel - administration & dosage; Prognosis; Prospective Studies; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Remission Induction; Research Article; Survival Rate; Trastuzumab; Neoadjuvant chemotherapy; Pathological complete response; Breast cancer; Dose-dense; Outcome; Histological subtypes
• ISSN: 1699-048X; 1699-3055
• DOI: 10.1007/s12094-013-1116-z

Purpose To assess the impact in pathological complete response (pCR) and outcome of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different histological subtypes determined by hormonal receptor (HR) and HER2 status in breast cancer patients. Methods A total of 127 breast cancer patients were treated with DDNC in two prospective studies. A: adriamycin 40 mg/m 2 on day (d) 1 plus paclitaxel 150 mg/m 2 and gemcitabine 2,000 mg/m 2 on d2 for six cycles ( n  = 54). B: epirubicin 90 mg/m 2 , cyclophosphamide 600 mg/m 2 on d1 for three cycles, followed by paclitaxel 150 mg/m 2 and gemcitabine 2,500 mg/m 2 on d1 ± trastuzumab according to HER2 status ( n  = 73). Histological subtypes of breast cancer were 49 % HR+/HER2−, 17.5 % HR+/HER2+, 13.5 % HR−/HER2+ and 20 % HR−/HER2−. Results pCR (absence of invasive cells in breast and lymph node) was achieved in 35 patients (28 %). The pCR rate was significantly different between histological subtypes: HR+/HER2− (9 %), HR+/HER2+ (23 %), HR−/HER2+ (50 %), HR−/HER2− (56 %) ( p  < 0.001). The median follow-up was 81 months (r: 15–150 months). HR−/HER2− tumor subtype had a significantly worse DFS compared to HR+/HER2− ( p  = 0.02), RH+/HER2+ ( p  = 0.04) and HR−/HER2+ tumor subtypes ( p  = 0.02). HR−/HER2− tumor subtype had a significantly shorter OS compared to HR+/HER2− ( p  = 0.007), RH+/HER2+ ( p  = 0.05), and HR−/HER2+ ( p  = 0.03) tumor subtypes. However, no significant difference was observed in DFS and OS among HR−/HER2− tumors that achieved a pCR. Conclusions HR−/HER2− and HR−/HER2+ subtypes had a high pCR rate to DDNC. HR−/HER2− tumors had a worse outcome compared to other tumor subtypes but no significant difference was observed among HR−/HER2− tumors that achieved a pCR.