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Abstract
Introduction. Previous studies have indicated that the addition of carboplatin to neoadjuvant chemotherapy (NACT) in patients with early triple-negative breast cancer (TNBC) is associated with an increased rate of pathological complete response (pCR). However, the subgroup of patients who truly benefit from the addition of platinum agents has yet to be identified. Tumor infiltrating lymphocytes (TILs) are reliable prognostic and predictive biomarker in TNBC.
Aim. To evaluate the efficacy of platinum-containing and platinum-free NACT depending on the level of TILs.
Materials and Methods. The retrospective study included data on 140 patients with TNBC (ER < 10 %) treated at the N.N. Petrov National Medical Research Center of Oncology between 2017 and 2023. The patients were divided into two groups: the control group (n = 70) received standard NACT, while the comparison group (n = 70) was treated with NACT including platinum agents. The level of TILs was evaluated in biopsy material and was classified into two groups: high (> 40 %) and low (≤ 40 %). The primary endpoint of the study was the pathological complete response (pCR) rate, while the secondary endpoint was event-free survival (EFS).
Results. The pCR rate was significantly higher in the NACT group with platinum agents (64.3 %), compared to the group without platinum (35.7 %) (OR 3.24, 95 % CI 1.62-6.47; p = 0.001). There was no statistically significant difference in the pCR rates between the carboplatin-based and standard NACT groups with high TILs, with 68.4 % and 53.3 %, respectively (OR 1.90; 95 % CI 0.47-7.70; p = 0.369). In the low TILs group, the pCR was more frequent in the platinum-based NACT group (62.7 %) compared to the standard NACT group (32.7 %) (OR 3.46; 95 % CI 1.56-7.70; p = 0.002). There were no significant differences in EFS depending on the NACT regimen (p = 0.161). A high TILs was associated with a higher 3-year EFS rate of 95 % compared to 65 % in the low TIL level group (OR 9.095, 95 % CI 1.232-0.859; p = 0.030). Multivariate analysis revealed predictors significantly associated with EFS: high TILs (0.024), pCR (0.038) and stage (0.025).
Conclusion. Low level of TILs is a poor prognostic factor in patients with early TNBC. The incorporation of platinum agents is a viable option primarily for TNBC patients with low TILs levels. These data can help in personalizing the treatment of patients with TNBC.
References
Schmid P., Cortes J., Pusztai L., et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020; 382(9): 810-821.-DOI: https://doi.org/10.1056/NEJMoa1910549.
Gao Z.H., Li C.X., Liu M., Jiang J.Y. Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis. BMC Cancer. 2020; 20(1).-DOI: https://doi.org/10.1186/S12885-020-07654-Y.
Issa-Nummer Y., Darb-Esfahani S., Loibl S., et al. Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial. PLoS One. 2013; 8(12).-DOI: https://doi.org/10.1371/JOURNAL.PONE.0079775.
García-Martínez E., Gil G.L., Benito A.C., et al. Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer. Breast Cancer Res. 2014; 16(6).-DOI: https://doi.org/10.1186/S13058-014-0488-5.
Mao Y., Qu Q., Zhang Y., et al. The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis. PLoS One. 2014; 9(12).-DOI: https://doi.org/10.1371/JOURNAL.PONE.0115103.
Semiglazov V.F. Dependence of clinical course in breast cancer on tumour pathology. Radiobiol Radiother (Berl). 1974; 15(3): 361-364.
Палтуев Р. М., Кудайбергенова А. Г., Семиглазов В. Ф., et al. Прогностические возможности CD4+ при раке молочной железы Т1–2N0M0. Опухоли женской репродуктивной системы. 2023; 19(2): 89-93.-DOI: https://doi.org/10.17650/1994-4098-2023-19-2-89-93. [Paltuev R.M., Kudaybergenova A.G., Semiglazov V.F., et al. Prognostic value of CD4+ in patients with Т1–2N0M0 breast cancer. Tumors of Female Reproductive System. 2023; 19(2): 89-93.-DOI: https://doi.org/10.17650/1994-4098-2023-19-2-89-93. (In Rus)].
Von Minckwitz G., Schneeweiss A., Loibl S., et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014; 15(7): 747-756.-DOI: https://doi.org/10.1016/S1470-2045(14)70160-3.
Sikov W.M., Berry D.A., Perou C.M., et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). Journal of Clinical Oncology. 2015; 33(1): 13.-DOI: https://doi.org/10.1200/JCO.2014.57.0572.
Loibl S., O’Shaughnessy J., Untch M., et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018; 19(4): 497-509.-DOI: https://doi.org/10.1016/S1470-2045(18)30111-6.
Poggio F., Bruzzone M., Ceppi M., et al. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis. Ann Oncol. 2018; 29(7): 1497-1508.-DOI: https://doi.org/10.1093/ANNONC/MDY127.
Salgado R., Denkert C., Demaria S., et al. International TILs Working Group 2014. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015; 26(2): 259-71.-DOI: https://doi.org/10.1093/annonc/mdu450.
Bianchini G., Huang C.S., Egle D., et al. LBA13 Tumour infiltrating lymphocytes (TILs), PD-L1 expression and their dynamics in the NeoTRIPaPDL1 trial. Ann Oncol. 2020; 31: S1145-S1146.-DOI: https://doi.org/10.1016/j.annonc.2020.08.2241.
Schmid P., Salgado R., Park Y.H., et al. Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study. Ann Oncol. 2020; 31(5): 569-581.-DOI: https://doi.org/10.1016/J.ANNONC.2020.01.072.
Herrero-Vicent C., Guerrero A., Gavilá J., et al. Predictive and prognostic impact of tumour-infiltrating lymphocytes in triple-negative breast cancer treated with neoadjuvant chemotherapy. Ecancermedicalscience. 2017; 11.-DOI: https://doi.org/10.3332/ECANCER.2017.759.
Abdullaeva S., Semiglazova T.Y., Artemyeva A., et al. 264P Tumor-infiltrating lymphocytes (TILs) for prediction of response to platinum-based neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC): Final analysis. Ann Oncol. 2023; 34: S288-S289.-DOI: https://doi.org/10.1016/j.annonc.2023.09.461.
Бузенкова А.В., Таширева Л.А., Завьялова М.В., et al. Особенности клеточного состава опухолевой ниши инвазивной протоковой карциномы неспецифического типа молочной железы. Сибирский онкологический журнал. 2022; 21(5): 59-68.-DOI: https://doi.org/10.21294/1814-4861-2022-21-5-59-68. [Buzenkova A.V., Tashireva L.A., Zavyalova M.V., et al. The features of tumor niche cell composition in invasive breast ductal carcinoma of no special type. Siberian Journal of Oncology. 2022; 21(5): 59-68.-DOI: https://doi.org/10.21294/1814-4861-2022-21-5-59-68. (In Rus)].
Семиглазов В.Ф., Целуйко А.И., Балдуева И.А., et al. Иммунология и иммунотерапия в комплексном лечении злокачественных опухолей. Медицинский совет. 2021; (4): 248-257.-DOI: https://doi.org/10.21518/2079-701X-2021-4-248-257. [Semiglazov V.F., Tseluiko A.I., Baldueva I.A., et al. Immunology and immunotherapy in the complex treatment of malignant tumors. Meditsinskiy Sovet = Medical Council. 2021; (4): 248-257.-DOI: https://doi.org/10.21518/2079-701X-2021-4-248-257. (In Rus)].
Tovey H., Sipos O., Parker J.S., et al. Integrated multimodal analyses of DNA damage response and immune markers as predictors of response in metastatic triple-negative breast cancer in the TNT trial (NCT00532727). Clin Cancer Res. 2023; 29(18): 3691-3705.-DOI: https://doi.org/10.1158/1078-0432.CCR-23-0370.
Lesterhuis W.J., Punt C.J.A, Hato S.V., et al. Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice. J Clin Invest. 2011; 121(8): 3100.-DOI: https://doi.org/10.1172/JCI43656.
Denkert C., Von Minckwitz G., Brase J.C., et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015; 33(9): 983-991.-DOI: https://doi.org/10.1200/JCO.2014.58.1967.
Hsu J.Y., Chang C.J., Cheng J.S. Survival, treatment regimens and medical costs of women newly diagnosed with metastatic triple-negative breast cancer. Sci Rep. 2022; 12(1).-DOI: https://doi.org/10.1038/S41598-021-04316-2.
Cortazar P., Zhang L., Untch M., et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014; 384(9938): 164-172.-DOI: https://doi.org/10.1016/S0140-6736(13)62422-8.
Loi S., Drubay D., Adams S., et al. Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol. 2019; 37(7): 559-569.-DOI: https://doi.org/10.1200/JCO.18.01010.
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