Neoadjuvant chemotherapy and pathological complete response in hormone-positive HER2-negative breast cancer: influence of progesterone receptor expression, tumor grade and Ki-67

Aim. To study the role of progesterone receptor expression, tumor grade and Ki-67 level as possible predictors of pathological complete response (pCR) to neoadjuvant chemotherapy in patients with stage IIA–IIB (cT1–2N1, cT2–3N0M0) breast cancer of hormone-positive HER2-negative subtype.

Materials and methods. We retrospectively analysed the efficacy of neoadjuvant chemotherapy (4AC+12P/4T) in 100 patients with cancer stages IIA–IIB (cT1–2N1, cT2–3N0M0) of hormone-positive HER2-negative subtype treated at the P.A. Hertsen Moscow Oncology Research Institute from 2013 to 2022. The pathological response to neoadjuvant chemotherapy depending on the level of progesterone receptor expression, tumour grade (G) and tumour proliferation index (Ki-67) were evaluated.

Results. Pathological complete response was achieved in 12 of 100 patients. The progesterone receptor expression ≤3 Allred pCR scores were found in 16.1 % (5/31) of patients, whereas with progesterone receptor >3 scores in 10.1 % (7/69) (odds ratio 1.703; 95 % confidence interval (CI) 0.495–5.860; p = 0.507). Patients with high tumour grade (G3) achieved pCR in 12.1 % (4/33) cases and with G2 – in 11.9 % (8/67) (odds ratio 1.017; 95 % CI 0.283–3.658; p = 1.000). With the Ki-67 levels ≥50 % pCR was achieved in 14.6 % (7/48) cases compared to 9.6 % (5/52) with Ki-67 levels <50 %(odds ratio 1.605; 95 % CI 0.473–5.445; p = 0.544). The Ki-67 threshold for achieving pCR was 70 % (area under the ROC curve 0.663 ± 0.090; 95 % CI 0.486–0.840; p = 0.068) and for progesterone receptors was 3 points (area under the ROC curve 0.625 ± 0.080; 95 % CI 0.467–0.782; p = 0.156).

Conclusion. This analysis highlights the importance of considering all clinical and morphological characteristics of the tumour when planning the scope of treatment for hormone-positive HER2-negative breast cancer. The results obtained may serve as a basis for a more personalised therapeutic approach.

1. Malignant neoplasms in Russia in 2023 (morbidity and mortality). Eds.: A.D. Kaprin, V.V. Starinskiy, A.O. Shakhzadova. Moscow: MNIOI im. P.A. Gertsena - filial FGBU “NMITS radiologii” Minizdrava Rosii, 2024. 276 p. (In Russ.).

2. Allison K.H., Hammond M.E.H., Dowsett M. et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol 2020;38(12):1346-66. DOI: 10.1200/JCO.19.02309

3. Burstein H.J. Systemic therapy for estrogen receptor-positive, HER2-negative breast cancer. N Engl J Med 2020;383(26):2557-70. DOI: 10.1056/NEJMra1307118

4. Cortazar P., Zhang L., Untch M. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [published correction appears in Lancet 2019;393(10175):986]. Lancet 2014;384(9938):164-72. DOI: 10.1016/S0140-6736(13)62422-8

5. Hamy A.S., Darrigues L., Laas E. et al. Prognostic value of the residual cancer burden index according to breast cancersubtype: validation on a cohort of BC patients treated by neoadjuvant chemotherapy. PLoS One 2020;15(6):e0234191. DOI: 10.1371/journal.pone.0234191

6. Van Mackelenbergh M.T., Denkert C., Nekljudova V. et al. Outcome after neoadjuvant chemotherapy in estrogen receptorpositive and progesterone receptor-negative breast cancer patients: a pooled analysis of individual patient data from ten prospectively randomized controlled neoadjuvant trials. Breast Cancer Res Treat 2018;167(1):59-71. DOI: 10.1007/s10549-017-4480-5

7. Pease A.M., Riba L.A., Gruner R.A. et al. Oncotype DX® recurrence score as a predictor of response to neoadjuvant chemotherapy. Ann Surg Oncol 2019;26(2):366-71. DOI: 10.1245/s10434-018-07107-8

8. Wajid S., Samad F.A., Syed A.S., Kazi F. Ki-67 and its relation with complete pathological response in patients with breast cancer. Cureus 2021;13(7):e16788. DOI: 10.7759/cureus.16788

9. Akay E., Eren S.K., Özhan N.et al. The value of potential immunohistochemical biomarkers and clinicopathological findings in predicting response to neoadjuvant chemotherapy in breast cancer. Eur Rev Med Pharmacol Sci 2022;26(19):7070-83. DOI: 10.26355/eurrev_202210_29892

10. Petruolo O.A., Pilewskie M., Patil S. et al. Standard pathologic features can be used to identify a subset of estrogen receptorpositive, HER2 negative patients likely to benefit from neoadjuvant chemotherapy. Ann Surg Oncol 2017;24(9):2556-62. DOI: 10.1245/s10434-017-5898-z

11. Tang L., Shu X., Tu G. Exploring the influencing factors of the pathologic complete response in estrogen receptor-positive, HER2-negative breast cancer after neoadjuvant chemotherapy: a retrospective study. World J Surg Oncol 2022;20(1):27. DOI: 10.1186/s12957-022-02492-7

12. Boland M.R., Ryan É.J., Nugent T. et al. Impact of progesterone receptor status on response to neoadjuvant chemotherapy in estrogen receptor-positive breast cancer patients. J Surg Oncol 2020;122(5):861-8. DOI: 10.1002/jso.26096

13. Omranipour R., Jalili R., Yazdankhahkenary A. et al. Evaluation of pathologic complete response (pCR) to neoadjuvant chemotherapy in Iranian breast cancer patients with estrogen receptor positive and HER2 negative and impact of predicting variables on pCR. Eur J Breast Health 2020;16(3):213-8. DOI: 10.5152/ejbh.2020.5487

14. Yan S., Wang W., Zhu B. et al. Construction of nomograms for predicting pathological complete response and tumor shrinkage size in breast cancer. Cancer Manag Res 2020;12:8313-23. DOI: 10.2147/CMAR.S270687

15. Akdag G., Yildirim S., Dogan A. et al. Neoadjuvant chemotherapy and pathologic complete response in HR+/HER2- breast cancer: impact of tumor Ki67 and ER status. Chemotherapy 2024;69(3): 141-9. DOI: 10.1159/000537874

16. Jain P., Doval D.C., Batra U. et al. Ki-67 labeling index as a predictor of response to neoadjuvant chemotherapy in breast cancer. Jpn J Clin Oncol 2019;49(4):329-38. DOI: 10.1093/jjco/hyz012.