@article{3bb571c401894c0fbdb88626ac671c3c,
title = "Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial",
abstract = "Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab. {\textcopyright} 2019 UICC",
keywords = "adjuvant chemotherapy, breast cancer, dose-dense, HER2, trastuzumab",
author = "M. Lambertini and F. Poggio and M. Bruzzone and B. Conte and C. Bighin and {de Azambuja}, E. and M. Giuliano and {De Laurentiis}, M. and F. Cognetti and A. Fabi and G. Bisagni and A. Durando and A. Turletti and Y. Urracci and O. Garrone and F. Puglisi and F. Montemurro and M. Ceppi and {Del Mastro}, L. and investigators, {on behalf of the GIM2}",
note = "Export Date: 24 February 2020 CODEN: IJCNA Correspondence Address: Lambertini, M.; Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San MartinoItaly; email: matteo.lambertini@unige.it References: Sonnenblick, A., Piccart, M., Adjuvant systemic therapy in breast cancer: quo vadis? (2015) Ann Oncol, 26, pp. 1629-1634; Waks, A.G., Winer, E.P., Breast cancer treatment: a review (2019) JAMA, 321, pp. 288-300; Caparica, R., Bruzzone, M., Poggio, F., Anthracycline and taxane-based chemotherapy versus docetaxel and cyclophosphamide in the adjuvant treatment of HER2-negative breast cancer patients: a systematic review and meta-analysis of randomized controlled trials (2019) Breast Cancer Res Treat, 174, pp. 27-37; Peto, R., Davies, C., Godwin, J., Gray, R., Pan, H.C., Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials (2012) Lancet, 379, pp. 432-444; Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials (2019) Lancet, 393, pp. 1440-1452; Del Mastro, L., Bruzzi, P., Nicol{\`o}, G., HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients (2005) Br J Cancer, 93, pp. 7-14; Denduluri, N., Chavez-MacGregor, M., Telli, M.L., Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO clinical practice guideline focused update (2018) J Clin Oncol, 36, pp. 2433-2443; Morris, P.G., Iyengar, N.M., Patil, S., Long-term cardiac safety and outcomes of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab with and without lapatinib in patients with early breast cancer (2013) Cancer, 119, pp. 3943-3951; Fountzilas, G., Dafni, U., Papadimitriou, C., Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic cooperative oncology group randomized phase III trial (2014) BMC Cancer, 14, p. 515; Mavroudis, D., Saloustros, E., Malamos, N., Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic oncology research group (HORG) (2015) Ann Oncol, 26, pp. 1333-1340; Hurvitz, S.A., Dose intensification of chemotherapy for early breast cancer in the age of de-escalation (2019) Lancet, 393, pp. 1390-1392; Del Mastro, L., De Placido, S., Bruzzi, P., Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial (2015) Lancet, 385, pp. 1863-1872; Lambertini, M., Ceppi, M., Cognetti, F., Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: a pooled analysis of the MIG1 and GIM2 phase III studies (2017) Eur J Cancer, 71, pp. 34-42; Lambertini, M., Bruzzi, P., Poggio, F., Pegfilgrastim administration after 24 or 72 or 96 h to allow dose-dense anthracycline- and taxane-based chemotherapy in breast cancer patients: a single-center experience within the GIM2 randomized phase III trial (2016) Support Care Cancer, 24, pp. 1285-1294; Di Leo, A., Gancberg, D., Larsimont, D., HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil (2002) Clin Cancer Res, 8, pp. 1107-1116; Lambertini, M., Pond{\'e}, N.F., Solinas, C., Adjuvant trastuzumab: a 10-year overview of its benefit (2017) Expert Rev Anticancer Ther, 17, pp. 61-74; Tolaney, S.M., Guo, H., Pernas, S., Seven-year follow-up analysis of adjuvant paclitaxel and Trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer (2019) J Clin Oncol, 37, pp. 1868-1875; Foukakis, T., Papakonstantinou, A., Matikas, A., Tailored dose-dense chemotherapy in combination with trastuzumab as adjuvant therapy for HER2-positive breast cancer: a secondary analysis of the phase III PANTHER trial (2019) J Clin Oncol, 37; Brand{\~a}o, M., Pond{\'e}, N.F., Poggio, F., Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects (2018) Expert Rev Anticancer Ther, 18, pp. 629-649; Schneeweiss, A., Chia, S., Hickish, T., Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA) (2013) Ann Oncol, 24, pp. 2278-2284; Gianni, L., Pienkowski, T., Im, Y.-H., 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial (2016) Lancet Oncol, 17, pp. 791-800; von Minckwitz, G., Huang, C.-S., Mano, M.S., Trastuzumab Emtansine for residual invasive HER2-positive breast cancer (2019) N Engl J Med, 380, pp. 617-628; Lambertini, M., Campbell, C., Gelber, R.D., Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer: exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial (2019) Breast Cancer Res Treat, 177, pp. 103-114; Foukakis, T., von Minckwitz, G., Bengtsson, N.-O., Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: a randomized clinical trial (2016) JAMA, 316, pp. 1888-1896",
year = "2019",
month = nov,
day = "13",
doi = "10.1002/ijc.32789",
language = "English",
journal = "Int. J. Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
}