Abstract
Purpose
Endocrine therapy is one of the cornerstones of early breast cancer treatment. While this medication could be initiated on the day of diagnosis, it is often postponed until after completion of surgery, radiotherapy, and chemotherapy. This practice is based on preclinical data suggesting an antagonistic effect between endocrine therapy and cytostatic agents, and on the interpretation of clinical trials comparing concurrent versus sequential use of tamoxifen and chemotherapy. These clinical trials, however, have never shown a statistically significant difference in overall survival or disease-free survival and focused on tamoxifen rather than aromatase inhibitors. Nevertheless, sequentially administered endocrine and chemotherapy have become standard of care worldwide.
Results
We performed a literature review and conclude that concurrent endocrine chemotherapy is at least as effective as sequential treatment. In fact, higher response rates have been observed in trials with aromatase inhibitors rather than tamoxifen in a neoadjuvant setting.
Conclusion
We encourage breast cancer oncologists to re-consider concurrent endocrine chemotherapy as a possible treatment strategy enabling early start of potentially curative endocrine treatment.
Similar content being viewed by others
Data availability
Not applicable.
Code availability
Not applicable.
References
Curigliano G, Burstein HJ, Winer EP et al (2017) De-escalating and escalating treatments for early-stage breast cancer the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol 28:1700–1712
Semiglazov VFSV, Dashyan GA et al (2007) Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer 110:244–254
Wang DYFR, Liss SN, Edwards EA (2004) Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1. Mol Endocrinol 18(2):402–411
Ali SCR (2002) Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Cancer 2:101–112
Goldhirsch A, Glick J, Gelber RD (2005) International expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 16(10):1569–1583
Osborne CK, Kitten L, Arteaga CL (1989) Antagonism of chemotherapy-induced cytotoxicity for human breast cancer cells by antiestrogens. J Clin Oncol 7:710–717
Hug VHG, Drewinko B et al (1985) Tamoxifen-citrate counteracts the antitumor effects of cytotoxic drugs in vitro. J Clin Oncol 3:1672–1677
Kurebayashi J, Nukatsuka M, Nagase H et al (2007) Additive antitumor effect of concurrent treatment of 4-hydroxy tamoxifen with 5-fluorouracil but not with doxorubicin in estrogen receptor-positive breast cancer cells. Cancer Chemother Pharamcol 59:515–525
Bedognetti DSMR, Pronzato P et al (2011) Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: a multicenter randomized phase III trial. J Natl Can Inst 103(20):1529–1539
Albain KS, Barlow WE, Ravdin PM et al (2009) A randomized trial of adjuvant chemotherapy and tamoxifen timing in postmenopausal, endocrine-responsive, node-positive breast cancer. Lancet 374(9707):2055–2063
Pico C, Martin M, Jara C et al (2004) Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients. A GEICAM 9401 study. Ann Oncol 15(1):79–87
Poggio FCM, Lambertini M et al (2017) Concurrent versus sequential adjuvant chemo-endocrine therapy in hormone-receptor positive early stage breast cancer patients: a systematic review and meta-analysis. Breast 33:104–108
Pritchard KI (2008) Combining endocrine agents with chemotherapy: which patients and what sequence? Cancer 112:718–722
Del Mastro LDB, Atini E et al (2008) Timing of adjuvant chemotherapy and tamoxifen in women with breast cancer: findings from two consecutive trials of Gruppo Oncologico Nord-Ovest-Mammella Intergruppo (GONO-MIG) Group. Ann Oncol 19(2):299–307
Yu K-D, Wu S-Y, Liu G-Y et al (2019) Concurrent neoadjuvant chemotherapy and estrogen deprivation in patients with estrogen receptor–positive, human epidermal growth factor receptor 2–negative breast cancer (CBCSG-036): a randomized, controlled, multicenter trial. Cancer 125(13):2185
Mohammadianpanah M, Ashouri Y, Hoseini S, Amadloo N, Talei A, Tahmasebi S, Nasrolahi H, Mosalaei A, Omidvari S, Ansari M et al (2012) The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial. Breast Cancer Res Treat 132(3):853–861
Matsunuma R, Watanabe T, Hozumi Y, Koizumi K, Ito Y, Maruyama S, Ogura H, Goto K, Mori H, Sawai N et al (2020) Preoperative concurrent endocrine therapy with chemotherapy in luminal B-like breast cancer. Breast Cancer 27:819
Watanabe N, Ootawa Y, Kodama K, Kaide A, Ootsuka N, Matsuoka J (2010) Concurrent administration of chemo-endocrine therapy for postmenopausal breast cancer patients. Breast Cancer 17(4):247–253
Torrisi RBV, Rotmensz N et al (2011) Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer. Breast Cancer Res Treat 126(2):431–441
Group EBCTC (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365(9472):1687–1717
Geurts YMWA, Bretveld R et al (2017) Patterns and predictors of first and subsequent recurrence in women with early breast cancer. Breast Cancer Res Treat 165(3):709–720
Gray R (2010) Anthracycline-based adjuvant chemotherapy in breast cancer. Lancet 375:1870–1871
Bramwell VHCPKI, Tu D et al (2010) A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada—Clinical Trials Group Trial, MA.12). Ann Oncol 21(2):283–290
Jenkins VAALM, Atkins L et al (2008) Effects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II). Lancet Oncol 9(10):953–961
Funding
This work was not funded.
Author information
Authors and Affiliations
Contributions
CFJ, MS, and GSS selected and collected data, and wrote the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors have declared no conflict of interest related to this work.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Jacobs, C.F., Soesan, M. & Sonke, G.S. Concurrent chemo-endocrine treatment for early hormone-positive breast cancer: a no-go???. Breast Cancer Res Treat 192, 485–489 (2022). https://doi.org/10.1007/s10549-021-06505-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-021-06505-z