Tolerability of dose-dense and standard regimens of neoadjuvant chemotherapy in estrogen receptor-positive/HER2-negative breast cancer: results of a prospective observational study

Background. Given the high prevalence of hormone-sensitive breast cancer in Russia and around the world, it is extremely important to address the issue of indications for neoadjuvant (NACT) or adjuvant chemotherapy, as well as the scope and regimens of treatment. The article presents the results of our own study, considers the problems of toxicity and tolerability of dose-dense and standard NACT regimens.

Aim. To study the tolerability of dose-dense and standard NACT regimens.

Materials and methods. The prospective study included 109 patients. 53 patients received dose-dense NACT as preoperative treatment, 56 – the standard NACT regimen.

Results. In dose-dense NACT, the frequency and severity of anemia (p = 0.038), hepatotoxicity (p <0.001), peripheral polyneuropathy (p <0.001) increased, but the frequency of delayed start of the cycle in general (p = 0.012) and delay due to neutropenia (p <0.001) decreased.

Conclusion. When planning preventive chemotherapy in the treatment of breast cancer (NACT or adjuvant chemotherapy), it is necessary to take into account not only the oncological results in increasing recurrence-free and overall survival, but also the tolerability of therapy.

1. Zhou W., Chen S., Xu F., Zeng X. Survival benefit of pure dosedense chemotherapy in breast cancer: a meta-analysis of randomized controlled trials. World J Surg Oncol 2018;16(1):144. DOI: 10.1186/s12957-018-1424-4

2. World Health Organization. Breast Cancer. 2018. Available at: https://www.who.int/cancer/prevention/diagnosis-screening/breast-cancer/en/ (accessed 27.12.2019).

3. Cardoso F., Kyriakides S., Ohno S. et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol 2021;32(2):284]. Ann Oncol 2019;30(10):1674. DOI: 10.1093/annonc/mdz189

4. Li J.J., Shao Z.M. Endocrine therapy as adjuvant or neoadjuvant therapy for breast cancer: selecting the best agents, the timing and duration of treatment. Chin Clin Oncol 2016;5(3):40. DOI: 10.21037/cco.2016.03.24

5. Jia Y., Song Y., Dong G. et al. Aberrant regulation of RAD51 promotes resistance of neoadjuvant endocrine therapy in ER-positive breast cancer. Sci Rep 2019;9(1):12939. DOI: 10.1038/s41598-019-49373-w

6. Kurozumi S., Yamaguchi Y., Matsumoto H. et al. Utility of Ki67 labeling index, cyclin D1 expression, and ER-activity level in postmenopausal ER-positive and HER2-negative breast cancer with neoadjuvant chemo-endocrine therapy. PLoS One 2019;14(5):e0217279. DOI: 10.1371/journal.pone.0217279

7. Newman L.A. Epidemiology of locally advanced breast cancer. Semin Radiat Oncol 2009;19(4):195–203. DOI: 10.1016/j.semradonc.2009.05.003

8. Tryfonidis K., Senkus E., Cardoso M.J., Cardoso F. Management of locally advanced breast cancer-perspectives and future directions [published correction appears in Nat Rev Clin Oncol 2015;12(6):312]. Nat Rev Clin Oncol 2015;12(3):147–62. DOI: 10.1038/nrclinonc.2015.13

9. El Saghir N.S., Adebamowo C.A., Anderson B.O. et al. Breast cancer management in low resource countries (LRCs): consensus statement from the breast health global initiative. Breast 2011;20(Suppl 2):S3–11. DOI: 10.1016/j.breast.2011.02.006

10. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG); Peto R., Davies C., Godwin J. et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials. Lancet 2012;379(9814):432–44. DOI: 10.1016/S0140-6736(11)61625-5

11. Citron M.L., Berry D.A., Cirrincione C. et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003;21(8):1431–9. DOI: 10.1200/jco.2003.09.081

12. Foukakis T., von Minckwitz G., Bengtsson N.O. et al. 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. JAMA 2016;316(18):1888–96. DOI: 10.1001/jama.2016.15865

13. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). 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. Lancet 2019;393(10179):1440–52. DOI: 10.1016/S0140-6736(18)33137-4

14. Podsada K., Ryan J.C., Orbaugh K. Optimizing palbociclib therapy across the age spectrum: hypothetical, illustrative case scenarios in HR+, HER2-metastatic breast cancer. J Adv Pract Oncol 2020;11(7):700–19. DOI: 10.6004/jadpro.2020.11.7.5

15. Danese M.D., O’Malley C., Lindquist K. et al. An observational study of the prevalence and incidence of comorbid conditions in older women with breast cancer. Ann Oncol 2012;23:1756e65. DOI: 10.1093/annonc/mdr486

16. Louwman W.J., Janssen-Heijnen M.L., Houterman S. et al. Less extensive treatment and inferior prognosis for breast cancer patient with comorbidity: a population-based study. Eur J Cancer 2005;41(5):779–85. DOI: 10.1016/j.ejca.2004.12.025

17. Edwards M.J., Campbell I.D., Lawrenson R.A., Kuper-Hommel M.J. Influence of comorbidity on chemotherapy use for early breast cancer: systematic review and meta-analysis. Breast Canc Res Treat 2017;165(1):17–39. DOI: 10.1007/s10549-017-4295-4

18. Søgaard M., Thomsen R.W., Bossen K.S. et al. The impact of comorbidity on cancer survival: a review. Clin Epidemiol 2013;5(Suppl 1):3–29. DOI: 10.2147/CLEP.S47150

19. Gelmon K., Walshe J.M., Mahtani R. et al. Efficacy and safety of palbociclib in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with preexisting conditions: a post hoc analysis of PALOMA-2. Breast 2021;59:321–6. DOI: 10.1016/j.breast.2021.07.017

20. Riseberg D. Treating elderly patients with hormone receptor-positive advanced breast cancer. Clin Med Insights Oncol 2015;9:65–73. DOI: 10.4137/CMO.S26067