Results of Neoadjuvant Chemotherapy in ER-Positive HER2/neu-Negative Breast Cancer After 2–8 Courses NAC in ER+ HER/Neu- BC
Abstract
Background: Neoadjuvant chemotherapy (NCT) is an optimal treatment for estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2/neu)-negative breast cancer. We evaluated the results after 2, 4, 6, and 8 courses.
Methods: We conducted a retrospective analysis of the effectiveness of 2 to 8 courses of NCT in 121 patients. NCT consisted of doxorubicin, endoxan, and docetaxel. After NCT, all patients received surgery, radiation, and endocrine therapy.
Results: In Group 2, treatment showed no effect in 1 case (4%), while partial response was observed in 6 cases (23%) and stabilization in 19 cases (73%). In the 4-course group, there was no treatment effect in 2 cases (6.5%), partial response in 15 cases (48.4%), and stabilization in 13 cases (41.9%). Additionally, 1 case (3.1%) achieved a pathologic complete response (pCR). In the 6-course group, 1 case (3.1%) showed no treatment effect, 18 cases (56.3%) had a partial response, and 8 cases (25%) exhibited stabilization. A pCR was achieved in 5 cases (15.6%). In the final group (8 courses), 1 case (3.1%) had no treatment response, 18 cases (56.3%) demonstrated partial response, and 4 cases (12.5%) showed stabilization, with 9 cases (28.1%) achieving pCR.
The 5-year cancer-specific survival rate ranged from 88.1 ± 6.4% to 96.8 ± 3.2%.
Conclusion: Two courses of NCT were ineffective. Tumor progression occurred in 3% to 6% of cases, while the Ki-67 index increased by 9.4% to 22.6%. A pCR was achieved in 3.2% to 15.6% of patients after 4 to 6 courses. Intermediate tumor biopsy can identify cases of treatment resistance or high chemosensitivity.
Full text article
References
Burstein HJ, Curigliano G, Thürlimann B, Weber WP, Poortmans P, Regan MM, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021 Oct;32(10):1216-1235. doi:10.1016/j.annonc.2021.06.023.
Breast cancer. NCCN Guidelines, Version 3.2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
Wang H, Mao X. Evaluation of the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer. Drug Des Devel Ther. 2020;14:2423-2433. doi:10.2147/DDDT.S253961.
Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, et al. Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: A systematic review and meta-analysis. JAMA Oncol. 2016;2(11):1477–1486. doi:10.1001/jamaoncol.2016.1897.
Sella T, Weiss A, Mittendorf EA, King TA, Pilewskie M, Giuliano AE, et al. Neoadjuvant endocrine therapy in clinical practice: A review. JAMA Oncol. 2021;7(11):1700–1708. doi:10.1001/jamaoncol.2021.2132.
Lerebours F, Pulido M, Fourme E, Debled M, Becette V, Bonnefoi H, et al. Predictive factors of 5-year relapse-free survival in HR+/HER2− breast cancer patients treated with neoadjuvant endocrine therapy: Pooled analysis of two phase 2 trials. Br J Cancer. 2020;122(6):759–765. doi:10.1038/s41416-020-0733-x.
López-Velazco JI, Manzano S, Otaño M, et al. A prospective study on tumour response assessment methods after neoadjuvant endocrine therapy in early oestrogen receptor-positive breast cancer. Breast Cancer Res. 2024;26(1):3. doi:10.1186/s13058-023-01756-8.
Karahan F, Yılmaz Bozok Y, Gökova M, Gürsoy Bulut M, Bolat Küçükzeybek B, Atahan MK. Clinicopathologic characteristics of breast cancer patients who had a pathologic complete response after neoadjuvant treatment. Ann Ital Chir. 2024;95(6):1240-1248. doi:10.62713/aic.3403.
Guarneri V, Dieci MV, Bisagni G, Frassoldati A, Bianchi GV, De Salvo GL, et al. De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole: Results of the PerELISA neoadjuvant study. Ann Oncol. 2019;30(6):921–926. doi:10.1093/annonc/mdz055.
Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, et al. Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol. 2017;35(10):1049–1060. doi:10.1200/JCO.2015.63.1010.
Gentile D, Sagona A, De Carlo C, Fernandes B, Barbieri E, Di Maria Grimaldi S, et al. Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients. Breast. 2023 Jun;69:323-329. doi:10.1016/j.breast.2023.03.016.
Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1—Update and clarification: From the RECIST committee. Eur J Cancer. 2016 Jul;62:132-137. doi:10.1016/j.ejca.2016.03.081.
Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol. 2020;38(12):1346–1366. doi:10.1200/JCO.19.02309.
Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(8):1194–1220. doi:10.1093/annonc/mdz173.
Martí C, Sánchez-Méndez JI. The present and future of neoadjuvant endocrine therapy for breast cancer treatment. Cancers. 2021;13(11):2538. doi:10.3390/cancers13112538.
Kurozumi S, Matsumoto H, Inoue K, Tozuka K, Hayashi Y, Kurosumi M, et al. Impact of combining the progesterone receptor and preoperative endocrine prognostic index (PEPI) as a prognostic factor after neoadjuvant endocrine therapy using aromatase inhibitors in postmenopausal ER-positive and HER2-negative breast cancer. PLoS ONE. 2018;13(8):e0201846. doi:10.1371/journal.pone.0201846.
Ellis MJ, Tao Y, Luo J, A’Hern R, Evans DB, Bhatnagar AS, et al. Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst. 2008;100(19):1380–1388. doi:10.1093/jnci/djn309.
Sinn BV, Sychra K, Untch M, Karn T, van Mackelenbergh M, Huober J, et al. On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res. 2024;26(1):138. doi:10.1186/s13058-024-01883-w.
Bliss JM, Tovey H, Evans A, Holcombe C, Horgan K, Mallon E, et al. Clinico-pathologic relationships with Ki67 and its change with short-term aromatase inhibitor treatment in primary ER+ breast cancer: Further results from the POETIC trial (CRUK/07/015). Breast Cancer Res. 2023;25(1):39. doi:10.1186/s13058-023-01626-3.
Jain P, Doval DC, Batra U, Goyal P, Bothra SJ, Agarwal C, et al. Ki-67 labeling index as a predictor of response to neoadjuvant chemotherapy in breast cancer. Jpn J Clin Oncol. 2019;49(4):329–338. doi:10.1093/jjco/hyz012.
Xu W, Chen X, Deng F, Zhang J, Zhang W, Tang J. Predictors of neoadjuvant chemotherapy response in breast cancer: A review. Onco Targets Ther. 2020;13:5887–5899. doi:10.2147/OTT.S253056.
Tan S, Fu X, Xu S, Qiu P, Lv Z, Xu Y, et al. Quantification of Ki67 change as a valid prognostic indicator of luminal B type breast cancer after neoadjuvant therapy. Pathol Oncol Res. 2021;27:1609972. doi:10.3389/pore.2021.1609972.
Lee J, Lee YJ, Bae SJ, Baek SH, Kook Y, Cha YJ, et al. Ki-67, 21-gene recurrence score, endocrine resistance, and survival in patients with breast cancer. JAMA Netw Open. 2023;6(8):e2330961. doi:10.1001/jamanetworkopen.2023.30961.
Miligy IM, Badr N, Stevens A, Spooner D, Awasthi R, Mir Y, et al. Pathological changes following neoadjuvant endocrine therapy (NAET): A multicentre study of 391 breast cancers. Int J Mol Sci. 2024;25(13):7381. doi:10.3390/ijms25137381.
Göker M, Denys H, Hendrix A, De Wever O, Van de Vijver K, Braems G. Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer. Breast Cancer Res. 2023;25(1):146. doi:10.1186/s13058-023-01745-x.
Petrelli F, Rea C, Parati MC, Borgonovo K, Ghilardi M, Dottorini L, et al. Prognostic value of HER2-low status in ER+ early breast cancer: A systematic review and meta-analysis. Anticancer Res. 2023;43(10):4303-4313. doi:10.21873/anticanres.16625.
Morrow M. Sentinel-lymph-node biopsy in early-stage breast cancer—Is it obsolete? N Engl J Med. 2024. doi:10.1056/NEJMe2414899.
Reimer T, Stachs A, Veselinovic K, Kühn T, Heil J, Polata S, et al. Axillary surgery in breast cancer—Primary results of the INSEMA trial. N Engl J Med. 2024. doi:10.1056/NEJMoa2412063.
Gentilini OD, Botteri E, Sangalli C, Galimberti V, Porpiglia M, Agresti R, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND randomized clinical trial. JAMA Oncol. 2023;9(11):1557-1564. doi:10.1001/jamaoncol.2023.3759.
Authors
Copyright (c) 2025 Archives of Breast Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.