Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies

M. Lambertini, M. Ceppi, F. Cognetti, G. Cavazzini, M. De Laurentiis, S. De Placido, A. Michelotti, G. Bisagni, A. Durando, E. Valle, T. Scotto, A. De Censi, A. Turletti, M. Benasso, S. Barni, F. Montemurro, F. Puglisi, A. Levaggi, S. Giraudi, C. BighinP. Bruzzi, L. Del Mastro

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Abstract

Background No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea. Patients and methods In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates. Results A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95% confidence intervals [CI], 0.54–0.95; p = 0.021). The pooled HRs were 0.78 (95% CI, 0.54–1.12) and 0.65 (95% CI, 0.40–1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95% CI, 0.80–1.25; p = 0.989). Conclusion Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients. © 2016 Elsevier Ltd
Original languageEnglish
Pages (from-to)227
Number of pages1
JournalEuropean journal of cancer
Volume71
DOIs
Publication statusPublished - 2017

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Adjuvant Chemotherapy
Breast Neoplasms
Amenorrhea
Drug Therapy
Confidence Intervals
Logistic Models
Epirubicin
Therapeutics
Paclitaxel
Proportional Hazards Models
Meta-Analysis
Randomized Controlled Trials
Odds Ratio
Hormones
Survival

Keywords

  • Breast cancer
  • Dose-dense chemotherapy
  • Premenopausal patients
  • Treatment-induced amenorrhoea

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Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies. / Lambertini, M.; Ceppi, M.; Cognetti, F.; Cavazzini, G.; De Laurentiis, M.; De Placido, S.; Michelotti, A.; Bisagni, G.; Durando, A.; Valle, E.; Scotto, T.; De Censi, A.; Turletti, A.; Benasso, M.; Barni, S.; Montemurro, F.; Puglisi, F.; Levaggi, A.; Giraudi, S.; Bighin, C.; Bruzzi, P.; Del Mastro, L.

In: European journal of cancer, Vol. 71, 2017, p. 227.

Research output: Contribution to journalArticle

Lambertini, M, Ceppi, M, Cognetti, F, Cavazzini, G, De Laurentiis, M, De Placido, S, Michelotti, A, Bisagni, G, Durando, A, Valle, E, Scotto, T, De Censi, A, Turletti, A, Benasso, M, Barni, S, Montemurro, F, Puglisi, F, Levaggi, A, Giraudi, S, Bighin, C, Bruzzi, P & Del Mastro, L 2017, 'Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies', European journal of cancer, vol. 71, pp. 227. https://doi.org/10.1016/j.ejca.2016.10.030
Lambertini, M. ; Ceppi, M. ; Cognetti, F. ; Cavazzini, G. ; De Laurentiis, M. ; De Placido, S. ; Michelotti, A. ; Bisagni, G. ; Durando, A. ; Valle, E. ; Scotto, T. ; De Censi, A. ; Turletti, A. ; Benasso, M. ; Barni, S. ; Montemurro, F. ; Puglisi, F. ; Levaggi, A. ; Giraudi, S. ; Bighin, C. ; Bruzzi, P. ; Del Mastro, L. / Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies. In: European journal of cancer. 2017 ; Vol. 71. pp. 227.
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title = "Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies",
abstract = "Background No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea. Patients and methods In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates. Results A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95{\%} confidence intervals [CI], 0.54–0.95; p = 0.021). The pooled HRs were 0.78 (95{\%} CI, 0.54–1.12) and 0.65 (95{\%} CI, 0.40–1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95{\%} CI, 0.80–1.25; p = 0.989). Conclusion Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients. {\circledC} 2016 Elsevier Ltd",
keywords = "Breast cancer, Dose-dense chemotherapy, Premenopausal patients, Treatment-induced amenorrhoea",
author = "M. Lambertini and M. Ceppi and F. Cognetti and G. Cavazzini and {De Laurentiis}, M. and {De Placido}, S. and A. Michelotti and G. Bisagni and A. Durando and E. Valle and T. Scotto and {De Censi}, A. and A. Turletti and M. Benasso and S. Barni and F. Montemurro and F. Puglisi and A. Levaggi and S. Giraudi and C. Bighin and P. Bruzzi and {Del Mastro}, L.",
note = "Cited By :3 Export Date: 14 July 2017 CODEN: EJCAE Correspondence Address: Del Mastro, L.; Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino – IST, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10, Italy; email: lucia.delmastro@hsanmartino.it References: Rosenberg, S.M., Newman, L.A., Partridge, A.H., Breast cancer in young women: rare disease or public health problem? (2015) JAMA Oncol, 1, pp. 877-878; Paluch-Shimon, S., Pagani, O., Partridge, A.H., Bar-Meir, E., Fallowfield, L., Fenlon, D., Second international consensus guidelines for breast cancer in young women (BCY2) (2016) Breast, 26, pp. 87-99; Cardoso, F., Loibl, S., Pagani, O., Graziottin, A., Panizza, P., Martincich, L., The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer (2012) Eur J Cancer, 48, pp. 3355-3377; Lambertini, M., Del Mastro, L., Pescio, M.C., Andersen, C.Y., Azim, H.A., Jr., Peccatori, F.A., Cancer and fertility preservation: international recommendations from an expert meeting (2016) BMC Med, 14, p. 1; Howard-Anderson, J., Ganz, P.A., Bower, J.E., Stanton, A.L., Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review (2012) J Natl Cancer Inst, 104, pp. 386-405; Ruddy, K.J., Gelber, S.I., Tamimi, R.M., Ginsburg, E.S., Schapira, L., Come, S.E., Prospective study of fertility concerns and preservation strategies in young women with breast cancer (2014) J Clin Oncol, 32, pp. 1151-1156; Bonilla, L., Ben-Aharon, I., Vidal, L., Gafter-Gvili, A., Leibovici, L., Stemmer, S.M., Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials (2010) J Natl Cancer Inst, 102, pp. 1845-1854; Petrelli, F., Cabiddu, M., Coinu, A., Borgonovo, K., Ghilardi, M., Lonati, V., Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials (2015) Breast Cancer Res Treat, 151, pp. 251-259; Fornier, M.N., Modi, S., Panageas, K.S., Norton, L., Hudis, C., Incidence of chemotherapy-induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane (2005) Cancer, 104, pp. 1575-1579; Abusief, M.E., Missmer, S.A., Ginsburg, E.S., Weeks, J.C., Partridge, A.H., The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer (2010) Cancer, 116, pp. 791-798; Venturini, M., Del Mastro, L., Aitini, E., Baldini, E., Caroti, C., Contu, A., Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial (2005) J Natl Cancer Inst, 97, pp. 1724-1733; Del Mastro, L., De Placido, S., Bruzzi, P., De Laurentiis, M., Boni, C., Cavazzini, G., 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., Bruzzi, P., Poggio, F., Pastorino, S., Gardin, G., Clavarezza, M., 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; Bianco, A.R., Del Mastro, L., Gallo, C., Perrone, F., Matano, E., Pagliarulo, C., Prognostic role of amenorrhea induced by adjuvant chemotherapy in premenopausal patients with early breast cancer (1991) Br J Cancer, 63, pp. 799-803; (2016), http://apps.who.int/iris/handle/10665/41526, World Health Organization (WHO) IRIS: research on the menopause. [Date last accessed 11 October]; DerSimonian, R., Laird, N., Meta-analysis in clinical trials (1986) Control Clin Trials, 7, pp. 177-188; Knapp, G., Hartung, J., Improved tests for a random effects meta-regression with a single covariate (2003) Stat Med, 22, pp. 2693-2710; Coates, A.S., Winer, E.P., Goldhirsch, A., Gelber, R.D., Gnant, M., Piccart-Gebhart, M., Tailoring therapies-improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015 (2015) Ann Oncol, 26, pp. 1533-1546; Denduluri, N., Somerfield, M.R., Eisen, A., Holloway, J.N., Hurria, A., King, T.A., Selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for human epidermal growth factor receptor 2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline (2016) J Clin Oncol, 34, pp. 2416-2427; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), 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; Lotrionte, M., Biondi-Zoccai, G., Abbate, A., Lanzetta, G., D'Ascenzo, F., Malavasi, V., Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity (2013) Am J Cardiol, 112, pp. 1980-1984; Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group (1998) Lancet, 352, pp. 930-942; Huober, J., von Minckwitz, G., Denkert, C., Tesch, H., Weiss, E., Zahm, D.M., Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study (2010) Breast Cancer Res Treat, 124, pp. 133-140; Azim, H.A., Partridge, A.H., Biology of breast cancer in young women (2014) Breast Cancer Res, 16, p. 427; Copson, E., Eccles, B., Maishman, T., Gerty, S., Stanton, L., Cutress, R.I., Prospective observational study of breast cancer treatment outcomes for UK women aged 18–40 years at diagnosis: the POSH study (2013) J Natl Cancer Inst, 105, pp. 978-988; H{\o}yer, M., Nordin, K., Ahlgren, J., Bergkvist, L., Lambe, M., Johansson, B., Change in working time in a population-based cohort of patients with breast cancer (2012) J Clin Oncol, 30, pp. 2853-2860; Lambertini, M., Boni, L., Michelotti, A., Gamucci, T., Scotto, T., Gori, S., Ovarian suppression with triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival: a randomized clinical trial (2015) JAMA, 314, pp. 2632-2640",
year = "2017",
doi = "10.1016/j.ejca.2016.10.030",
language = "English",
volume = "71",
pages = "227",
journal = "European Journal of Cancer",
issn = "0014-2964",
publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies

AU - Lambertini, M.

AU - Ceppi, M.

AU - Cognetti, F.

AU - Cavazzini, G.

AU - De Laurentiis, M.

AU - De Placido, S.

AU - Michelotti, A.

AU - Bisagni, G.

AU - Durando, A.

AU - Valle, E.

AU - Scotto, T.

AU - De Censi, A.

AU - Turletti, A.

AU - Benasso, M.

AU - Barni, S.

AU - Montemurro, F.

AU - Puglisi, F.

AU - Levaggi, A.

AU - Giraudi, S.

AU - Bighin, C.

AU - Bruzzi, P.

AU - Del Mastro, L.

N1 - Cited By :3 Export Date: 14 July 2017 CODEN: EJCAE Correspondence Address: Del Mastro, L.; Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino – IST, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10, Italy; email: lucia.delmastro@hsanmartino.it References: Rosenberg, S.M., Newman, L.A., Partridge, A.H., Breast cancer in young women: rare disease or public health problem? (2015) JAMA Oncol, 1, pp. 877-878; Paluch-Shimon, S., Pagani, O., Partridge, A.H., Bar-Meir, E., Fallowfield, L., Fenlon, D., Second international consensus guidelines for breast cancer in young women (BCY2) (2016) Breast, 26, pp. 87-99; Cardoso, F., Loibl, S., Pagani, O., Graziottin, A., Panizza, P., Martincich, L., The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer (2012) Eur J Cancer, 48, pp. 3355-3377; Lambertini, M., Del Mastro, L., Pescio, M.C., Andersen, C.Y., Azim, H.A., Jr., Peccatori, F.A., Cancer and fertility preservation: international recommendations from an expert meeting (2016) BMC Med, 14, p. 1; Howard-Anderson, J., Ganz, P.A., Bower, J.E., Stanton, A.L., Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review (2012) J Natl Cancer Inst, 104, pp. 386-405; Ruddy, K.J., Gelber, S.I., Tamimi, R.M., Ginsburg, E.S., Schapira, L., Come, S.E., Prospective study of fertility concerns and preservation strategies in young women with breast cancer (2014) J Clin Oncol, 32, pp. 1151-1156; Bonilla, L., Ben-Aharon, I., Vidal, L., Gafter-Gvili, A., Leibovici, L., Stemmer, S.M., Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials (2010) J Natl Cancer Inst, 102, pp. 1845-1854; Petrelli, F., Cabiddu, M., Coinu, A., Borgonovo, K., Ghilardi, M., Lonati, V., Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials (2015) Breast Cancer Res Treat, 151, pp. 251-259; Fornier, M.N., Modi, S., Panageas, K.S., Norton, L., Hudis, C., Incidence of chemotherapy-induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane (2005) Cancer, 104, pp. 1575-1579; Abusief, M.E., Missmer, S.A., Ginsburg, E.S., Weeks, J.C., Partridge, A.H., The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer (2010) Cancer, 116, pp. 791-798; Venturini, M., Del Mastro, L., Aitini, E., Baldini, E., Caroti, C., Contu, A., Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial (2005) J Natl Cancer Inst, 97, pp. 1724-1733; Del Mastro, L., De Placido, S., Bruzzi, P., De Laurentiis, M., Boni, C., Cavazzini, G., 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., Bruzzi, P., Poggio, F., Pastorino, S., Gardin, G., Clavarezza, M., 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; Bianco, A.R., Del Mastro, L., Gallo, C., Perrone, F., Matano, E., Pagliarulo, C., Prognostic role of amenorrhea induced by adjuvant chemotherapy in premenopausal patients with early breast cancer (1991) Br J Cancer, 63, pp. 799-803; (2016), http://apps.who.int/iris/handle/10665/41526, World Health Organization (WHO) IRIS: research on the menopause. [Date last accessed 11 October]; DerSimonian, R., Laird, N., Meta-analysis in clinical trials (1986) Control Clin Trials, 7, pp. 177-188; Knapp, G., Hartung, J., Improved tests for a random effects meta-regression with a single covariate (2003) Stat Med, 22, pp. 2693-2710; Coates, A.S., Winer, E.P., Goldhirsch, A., Gelber, R.D., Gnant, M., Piccart-Gebhart, M., Tailoring therapies-improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015 (2015) Ann Oncol, 26, pp. 1533-1546; Denduluri, N., Somerfield, M.R., Eisen, A., Holloway, J.N., Hurria, A., King, T.A., Selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for human epidermal growth factor receptor 2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline (2016) J Clin Oncol, 34, pp. 2416-2427; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), 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; Lotrionte, M., Biondi-Zoccai, G., Abbate, A., Lanzetta, G., D'Ascenzo, F., Malavasi, V., Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity (2013) Am J Cardiol, 112, pp. 1980-1984; Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group (1998) Lancet, 352, pp. 930-942; Huober, J., von Minckwitz, G., Denkert, C., Tesch, H., Weiss, E., Zahm, D.M., Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study (2010) Breast Cancer Res Treat, 124, pp. 133-140; Azim, H.A., Partridge, A.H., Biology of breast cancer in young women (2014) Breast Cancer Res, 16, p. 427; Copson, E., Eccles, B., Maishman, T., Gerty, S., Stanton, L., Cutress, R.I., Prospective observational study of breast cancer treatment outcomes for UK women aged 18–40 years at diagnosis: the POSH study (2013) J Natl Cancer Inst, 105, pp. 978-988; Høyer, M., Nordin, K., Ahlgren, J., Bergkvist, L., Lambe, M., Johansson, B., Change in working time in a population-based cohort of patients with breast cancer (2012) J Clin Oncol, 30, pp. 2853-2860; Lambertini, M., Boni, L., Michelotti, A., Gamucci, T., Scotto, T., Gori, S., Ovarian suppression with triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival: a randomized clinical trial (2015) JAMA, 314, pp. 2632-2640

PY - 2017

Y1 - 2017

N2 - Background No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea. Patients and methods In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates. Results A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95% confidence intervals [CI], 0.54–0.95; p = 0.021). The pooled HRs were 0.78 (95% CI, 0.54–1.12) and 0.65 (95% CI, 0.40–1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95% CI, 0.80–1.25; p = 0.989). Conclusion Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients. © 2016 Elsevier Ltd

AB - Background No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea. Patients and methods In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks. In the GIM2 study, node-positive patients were randomised to 4 cycles of dose-dense or standard-interval EC or FEC followed by 4 cycles of dose-dense or standard-interval paclitaxel. Using individual patient data, the hazard ratio (HR) for overall survival by means of a Cox proportional hazards model and the odds ratio for treatment-induced amenorrhoea through a logistic regression model were calculated for each study. A meta-analysis of the two studies was performed using the random effect model to compute the parameter estimates. Results A total of 1,549 patients were included. Dose-dense chemotherapy was associated with a significant improved overall survival as compared to standard-interval chemotherapy (HR, 0.71; 95% confidence intervals [CI], 0.54–0.95; p = 0.021). The pooled HRs were 0.78 (95% CI, 0.54–1.12) and 0.65 (95% CI, 0.40–1.06) for patients with hormone receptor-positive and -negative tumours, respectively (interaction p = 0.330). No increased risk of treatment-induced amenorrhoea was observed with dose-dense chemotherapy (odds ratio, 1.00; 95% CI, 0.80–1.25; p = 0.989). Conclusion Dose-dense adjuvant chemotherapy may be considered the preferred treatment option in high-risk premenopausal breast cancer patients. © 2016 Elsevier Ltd

KW - Breast cancer

KW - Dose-dense chemotherapy

KW - Premenopausal patients

KW - Treatment-induced amenorrhoea

U2 - 10.1016/j.ejca.2016.10.030

DO - 10.1016/j.ejca.2016.10.030

M3 - Article

VL - 71

SP - 227

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0014-2964

ER -