Impact of Carboplatin on Long-Term Survival after Neoadjuvant Chemotherapy in Non-Metastatic Triple-Negative Breast Cancer: An Algerian Cohort Study Carboplatin in TNBC survival
Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen receptor, progesterone receptor, and HER2 expression. Platinum agents such as carboplatin have been incorporated into neoadjuvant regimens to improve pathological complete response (pCR), but its long-term survival benefit remains unclear, particularly in North African populations.
Methods: We conducted a retrospective cohort study with prospective longitudinal follow-up of 183 Algerian women with non-metastatic TNBC who received neoadjuvant chemotherapy between February 2015 and February 2017 at the Pierre and Marie Curie Cancer Center, Algiers. Patients received six cycles of docetaxel plus anthracycline–cyclophosphamide (FAC60), with or without the addition of carboplatin (AUC5). After surgery, patients were followed for overall survival (OS) and event-free survival (EFS) until November 2024. Statistical analyses were performed using R version 4.3.2.
Results: The median age was 43 years; 74% were premenopausal. The pCR rate was significantly higher with carboplatin than without carboplatin (58% vs. 36%, p = 0.01). After a median follow-up of 103 (9-118) months, three-, five-, and eight-year OS rates in the carboplatin group were 89%, 83.5%, and 75.2%, respectively. However, carboplatin did not improve OS (p = 0.34) or EFS (p = 0.49). Achieving pCR was independently associated with better survival outcomes (EFS p < 0.001) and OS p < 0.001, respectively) in multivariate Cox regression models.
Conclusion: Among Algerian women with non-metastatic TNBC, adding carboplatin increased pCR rates but did not improve a long-term survival. Pathologic complete response was an independent predictor of favorable prognosis.
References
Hammond MEH, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. 2010;134(6):907–22. doi:10.5858/134.6.907.
Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update. Arch Pathol Lab Med. 2018;142(11):1364–82. doi:10.5858/arpa.2018-0902-SA
Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013. doi:10.1200/JCO.2013.50.9984
Zagami P, Carey LA. Triple negative breast cancer: pitfalls and progress. npj Breast Cancer. 2022;8(1):95. doi:10.1038/s41523-022-00468-0
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15):4429–34. doi:10.1158/1078-0432.CCR-06-3045
Memon AI, Ujjan ID, Bhatti AM. Management of the triple negative locally advanced breast cancer. In: S S, S E, editors. Breast Cancer Updates. London: IntechOpen; 2023. doi:10.5772/intechopen.110149
Bou Zerdan M, Ghorayeb T, Saliba F, Allam S, Bou Zerdan M, Yaghi M, et al. Triple negative breast cancer: updates on classification and treatment in 2021. Cancers (Basel). 2022;14(5):1253. doi:10.3390/cancers14051253
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72. doi:10.1016/S0140-6736(13)62422-8
Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol. 2021;39(13):1485–505. doi:10.1200/JCO.20.03399
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):1194–220. doi:10.1093/annonc/mdz173
Poggio F, Bruzzone M, Ceppi M, Pondé NF, La Valle G, Del Mastro L, et al. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: A systematic review and meta-analysis. Ann Oncol. 2018;29(7):1497–508. doi:10.1093/annonc/mdy127
Petrelli F, Coinu A, Borgonovo K, Cabiddu M, Ghilardi M, Lonati V, et al. The value of platinum agents as neoadjuvant chemotherapy in triple-negative breast cancers: A systematic review and meta-analysis. Breast Cancer Res Treat. 2014;144(2):223–32. doi:10.1007/s10549-014-2876-z
Mason SR, Willson ML, Egger SJ, Beith J, Dear RF, Goodwin A. Platinum chemotherapy for early triple-negative breast cancer. Breast. 2024;75:103712. doi:10.1016/j.breast.2024.103712
Pathak N, Sharma A, Elavarasi A, Sankar J, Deo SVS, Sharma DN, et al. Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level meta-analysis. Breast. 2022;64:7–18. doi:10.1016/j.breast.2022.04.006
Geyer CE, Sikov WM, Huober J, Rugo HS, Wolmark N, O’Shaughnessy J, et al. Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase III trial. Ann Oncol. 2022;33(4):384–94. doi:10.1016/j.annonc.2022.01.009
Loibl S, Weber KE, Timms KM, Elkin EP, Hahnen E, Fasching PA, et al. Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response—final results from GeparSixto. Ann Oncol. 2018;29(12):2341–7. doi:10.1093/annonc/mdy460
Shepherd JH, Ballman K, Polley MYC, Campbell JD, Fan C, Selitsky S, et al. CALGB 40603 (Alliance): Long-term outcomes and genomic correlates of response and survival after neoadjuvant chemotherapy with or without carboplatin and bevacizumab in triple-negative breast cancer. J Clin Oncol. 2022;40(12):1323–34. doi:10.1200/JCO.21.01506
Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9. doi:10.3322/caac.21388
Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, editors. WHO classification of tumours of the breast. 4th ed. Lyon: International Agency for Research on Cancer; 2012. 240 p.
Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957;11(3):359–77. doi:10.1038/bjc.1957.43
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10(16):5367–74. doi:10.1158/1078-0432.CCR-04-0220
Cheang MCU, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14(5):1368–76. doi:10.1158/1078-0432.CCR-07-1658
Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst. 2011;103(22):1656–64. doi:10.1093/jnci/djr393
Wu Q, Ma G, Deng Y, Luo W, Zhao Y, Li W, et al. Prognostic value of Ki-67 in patients with resected triple-negative breast cancer: A meta-analysis. Front Oncol. 2019;9:1068. doi:10.3389/fonc.2019.01068
Litton JK, Regan MM, Pusztai L, Rugo HS, Tolaney SM, Garrett-Mayer E, et al. Standardized definitions for efficacy end points in neoadjuvant breast cancer clinical trials: NeoSTEEP. J Clin Oncol. 2023;41(27):4433–42. doi:10.1200/JCO.23.00435
Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, 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). J Clin Oncol. 2015;33(1):13–21. doi:10.1200/JCO.2014.57.0572
Loibl S, O’Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, 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:10.1016/S1470-2045(18)30111-6
Petrelli F, Ghidini A, Rea C, Parati MC, Borgonovo K, Ghidini M, et al. Platinum dose in neoadjuvant therapy for triple-negative breast cancer: A systematic review and network meta-analysis. Curr Probl Cancer. 2024;50:101096. doi:10.1016/j.currproblcancer.2024.101096
Mason SRE, Willson ML, Egger SJ, Beith J, Dear RF, Goodwin A. Platinum-based chemotherapy for early triple-negative breast cancer. Cochrane Database Syst Rev. 2023;(9):CD014805. doi:10.1002/14651858.CD014805.pub2
Souad H, Zahia F, Abdelhak L, Karima S, Dalila S, Noureddine A. Descriptive study of triple negative breast cancer in Eastern Algeria. Pan Afr Med J. 2018;29:45. doi:10.11604/pamj.2018.29.45.12523
Gaceb H, Cherbal F, Bakour R, Ould-Rouis A, Mahfouf H. Clinicopathological and molecular study of triple-negative breast cancer in Algerian patients. Pathol Oncol Res. 2018;24(2):297–308. doi:10.1007/s12253-017-0242-2
Vihervuori H, Korpinen K, Autere TA, Repo H, Talvinen K, Kronqvist P. Varying outcomes of triple-negative breast cancer in different age groups-prognostic value of clinical features and proliferation. Breast Cancer Res Treat. 2022;196(3):471–82. doi:10.1007/s10549-022-06767-1
James M, Dixit A, Robinson B, Frampton C, Davey V. Outcomes for patients with non-metastatic triple-negative breast cancer in New Zealand. Clin Oncol (R Coll Radiol). 2019;31(1):17–24. doi:10.1016/j.clon.2018.09.006
Zhu JW, Charkhchi P, Adekunte S, Akbari MR. What is known about breast cancer in young women? Cancers (Basel). 2023;15(6):1917. doi:10.3390/cancers15061917
Nishimura R, Osako T, Okumura Y, Nakano M, Otsuka H, Fujisue M, et al. Triple negative breast cancer: an analysis of the subtypes and the effects of menopausal status on invasive breast cancer. J Clin Med. 2022;11(9):2331. doi:10.3390/jcm11092331
Srinath A, van Merode F, Rao SV, Pavlova M. Barriers to cervical cancer and breast cancer screening uptake in low- and middle-income countries: a systematic review. Health Policy Plan. 2023;38(4):509–27. doi:10.1093/heapol/czac104
Harborg S, Zachariae R, Olsen J, Johannsen M, Cronin-Fenton D, Bøggild H, et al. Overweight and prognosis in triple-negative breast cancer patients: a systematic review and meta-analysis. npj Breast Cancer. 2021;7(1):119. doi:10.1038/s41523-021-00325-6
Kumar S, Furrukh M, Al-Baimani K, Al-Ajmi A, Burney IA, Al-Moundhri MS. Outcomes of women with non-metastatic triple-negative breast cancer in Oman: A single-centre experience. Sultan Qaboos Univ Med J. 2019;19(3):e209–16. doi:10.18295/squmj.2019.19.03.006
Hamdi Y, Mighri N, Boujemaa M, Mejri N, Ben Nasr S, Ben Rekaya M, et al. Identification of eleven novel BRCA mutations in Tunisia: impact on the clinical management of BRCA related cancers. Front Oncol. 2021;11:674965. doi:10.3389/fonc.2021.674965
von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804. doi:10.1200/JCO.2011.38.8595
Lucas MW, Kelly CM. Optimal choice of neoadjuvant chemotherapy for HER2-negative breast cancer: Clinical Insights. Cancer Manag Res. 2022;14:2493–506. doi:10.2147/CMAR.S341466
Gündoǧdu A, Uluşahin M, Çekiç AB, Kazaz SN, Güner A. Pathological complete response and associated factors in breast cancer after neoadjuvant chemotherapy: A retrospective study. Turk J Surg. 2024;40(1):73–81. doi:10.47717/turkjsurg.2024.6308
von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, 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):747–56. doi:10.1016/S1470-2045(14)70160-3
de Pádua Souza C, Carneiro ASB, de Oliveira Lessa AC, Lacerda DC, Paiva CE, Zorzetto MMC, et al. Neoadjuvant carboplatin in triple-negative breast cancer: results from NACATRINE, a randomized phase II clinical trial. Breast Cancer Res Treat. 2023;202(1):57–65. doi:10.1007/s10549-023-07011-0
Elnaggar AA, Ismail SS, Elzawawy SF, Faheim RM, AbdelHakim KN. Effectiveness and safety of platinum based agents neoadjuvant chemotherapy on pathological complete response in triple negative breast cancer patients (a retrospective study). Ain Shams Med J. 2024;75(2):337–47. doi:10.21608/asmj.2024.280363.1262
Feng W, He Y, Xu J, Zhang H, Si Y, Xu J, et al. A meta-analysis of the effect and safety of platinum-based neoadjuvant chemotherapy in treatment of resectable triple-negative breast cancer. Anti-Cancer Drugs. 2022;33(1):e52–60. doi:10.1097/CAD.0000000000001196
da Silva JL, Rodrigues FR, de Mesquita GG, Fernandes PV, Thuler LCS, de Melo AC. Triple-negative breast cancer: Assessing the role of immunohistochemical biomarkers on neoadjuvant treatment. Breast Cancer Targets Ther. 2021;13:31–44. doi:10.2147/BCTT.S287320
Authors
Copyright (c) 2026 Samira Merah, Amal Kouchkar, Amel Ladjeroud, Riad Nasri, Amira Boughedra, Salma Hentabli, Abed Berber, Karine Benachour, Mustapha Oumouna
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.