AC + T, doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (4 cycles) followed by 12 cycles of weekly paclitaxel 80 mg/m2; AC + TCbP, doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (4 cycles) followed by 12 cycles of weekly paclitaxel 80 mg/m2 and carboplatin AUC 2; AC, doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (4 cycles). AUC: area under the curve; BC: breast cancer; RECIST: Response Evaluation Criteria In Solid Tumors; UICC: Union for International Cancer Control; WT: wild-type
We are cordially thankful to Dr. Priscilla Amankwah for her invaluable help in improving this manuscript.
Author contributions
AS: Conceptualization, Investigation, Formal analysis, Writing—review & editing. TG: Conceptualization, Investigation, Resources. DE: Data curation, Resources. AS, AI, and AN: Investigation. IB, PK, and AB: Resources, Supervision. EI: Conceptualization, Writing—original draft, Funding acquisition. All authors read and approved the submitted version.
Conflicts of interest
Evgeny Imyanitov who is the Editorial Board Member of Exploration of Targeted Anti-tumor Therapy had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest.
Ethical approval
The study was approved by the Institutional Review Board of the N.N. Petrov Institute of Oncology (protocol No.1, 23.01.2020).
Consent to participate
Informed consent to participate in the study was obtained from all participants.
Consent to publication
Not applicable.
Availability of data and materials
All datasets for this study are included in the manuscript and the supplementary files.
Funding
This study is supported by the Russian Science Foundation, grant number [21-75-30015]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection.Nat Rev Cancer. 2011;12:68–78. [DOI] [PubMed] [PMC]
Sung M, Giannakakou P. BRCA1 regulates microtubule dynamics and taxane-induced apoptotic cell signaling.Oncogene. 2014;33:1418–28. [DOI] [PubMed] [PMC]
Kriege M, Jager A, Hooning MJ, Huijskens E, Blom J, van Deurzen CH, et al. The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers.Cancer. 2012;118:899–907. [DOI] [PubMed]
Mersch J, Jackson MA, Park M, Nebgen D, Peterson SK, Singletary C, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian.Cancer. 2015;121:269–75.Erratum in: Cancer. 2015;121:2474–5. [DOI] [PubMed] [PMC]
Pritchard CC, Mateo J, Walsh MF, Sarkar ND, Abida W, Beltran H, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.N Engl J Med. 2016;375:443–53. [DOI] [PubMed] [PMC]
Kryklyva V, Pflüger MJ, Ouchene H, Volleberg-Gorissen H, Mensenkamp AR, Jonker MA, et al. Germline Pathogenic Variants in Patients with Pancreatic Ductal Adenocarcinoma and Extra-Pancreatic Malignancies: A Nationwide Database Analysis.Mod Pathol. 2025;38:100709. [DOI] [PubMed]
Spurdle AB, Couch FJ, Parsons MT, McGuffog L, Barrowdale D, Bolla MK, et al.; kConFab Investigators. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.Breast Cancer Res. 2014;16:3419. [DOI] [PubMed] [PMC]
Hyman DM, Zhou Q, Iasonos A, Grisham RN, Arnold AG, Phillips MF, et al. Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer.Cancer. 2012;118:3703–9. [DOI] [PubMed] [PMC]
Candido-dos-Reis FJ, Song H, Goode EL, Cunningham JM, Fridley BL, Larson MC, et al.; Australian Ovarian Cancer Study Group. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer.Clin Cancer Res. 2015;21:652–7. [DOI] [PubMed] [PMC]
Swisher EM, Kwan TT, Oza AM, Tinker AV, Ray-Coquard I, Oaknin A, et al. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).Nat Commun. 2021;12:2487. [DOI] [PubMed] [PMC]
Myers SP, Sevilimedu V, Barrio AV, Tadros AB, Mamtani A, Robson ME, et al. Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers.NPJ Breast Cancer. 2024;10:63. [DOI] [PubMed] [PMC]
Bardia A, Baselga J. Neoadjuvant therapy as a platform for drug development and approval in breast cancer.Clin Cancer Res. 2013;19:6360–70. [DOI] [PubMed]
Imyanitov EN, Yanus GA. Neoadjuvant therapy: theoretical, biological and medical consideration.Chin Clin Oncol. 2018;7:55. [DOI] [PubMed]
Böhm S, Faruqi A, Said I, Lockley M, Brockbank E, Jeyarajah A, et al. Chemotherapy Response Score: Development and Validation of a System to Quantify Histopathologic Response to Neoadjuvant Chemotherapy in Tubo-Ovarian High-Grade Serous Carcinoma.J Clin Oncol. 2015;33:2457–63. [DOI] [PubMed]
Sokolenko AP, Sokolova TN, Ni VI, Preobrazhenskaya EV, Iyevleva AG, Aleksakhina SN, et al. Frequency and spectrum of founder and non-founder BRCA1 and BRCA2 mutations in a large series of Russian breast cancer and ovarian cancer patients.Breast Cancer Res Treat. 2020;184:229–35. [DOI] [PubMed]
Sokolenko AP, Sultanova LV, Stepanov IA, Romanko AA, Venina AR, Sokolova TN, et al. Strong founder effect for BRCA1 c.3629_3630delAG pathogenic variant in Chechen patients with breast or ovarian cancer.Cancer Med. 2023;12:3167–71. [DOI] [PubMed] [PMC]
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy.J Clin Oncol. 2007;25:4414–22. [DOI] [PubMed]
Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips K, Mooij TM, Roos-Blom M, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.JAMA. 2017;317:2402–16. [DOI] [PubMed]
Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.JAMA. 2015;313:1347–61. [DOI] [PubMed] [PMC]
Gorodnova TV, Kotiv KB, Ivantsov AO, Mikheyeva ON, Mikhailiuk GI, Lisyanskaya AS, et al. Efficacy of Neoadjuvant Therapy With Cisplatin Plus Mitomycin C in BRCA1-Mutated Ovarian Cancer.Int J Gynecol Cancer. 2018;28:1498–506. [DOI] [PubMed]
Gorodnova TV, Sokolenko AP, Kondratiev SV, Kotiv KB, Belyaev AM, Berlev IV, et al. Mitomycin C plus cisplatin for systemic treatment of recurrent BRCA1-associated ovarian cancer.Invest New Drugs. 2020;38:1872–8. [DOI] [PubMed]
Kechin A, Boyarskikh U, Barinov A, Tanas A, Kazakova S, Zhevlova A, et al. A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia.Breast Cancer Res Treat. 2023;197:387–95. [DOI] [PubMed]
Yanus GA, Savonevich EL, Sokolenko AP, Romanko AA, Ni VI, Bakaeva EK, et al. Founder vs. non-founder BRCA1/2 pathogenic alleles: the analysis of Belarusian breast and ovarian cancer patients and review of other studies on ethnically homogenous populations.Fam Cancer. 2023;22:19–30. [DOI] [PubMed]
Page CL, Amuzu S, Rahimi K, Gotlieb W, Ragoussis J, Tonin PN. Lessons learned from understanding chemotherapy resistance in epithelial tubo-ovarian carcinoma from BRCA1and BRCA2mutation carriers.Semin Cancer Biol. 2021;77:110–26. [DOI] [PubMed]
Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer.J Clin Oncol. 2008;26:1275–81. [DOI] [PubMed]
Hahnen E, Lederer B, Hauke J, Loibl S, Kröber S, Schneeweiss A, et al. Germline Mutation Status, Pathological Complete Response, and Disease-Free Survival in Triple-Negative Breast Cancer: Secondary Analysis of the GeparSixto Randomized Clinical Trial.JAMA Oncol. 2017;3:1378–85. [DOI] [PubMed] [PMC]
Sharma P, López-Tarruella S, García-Saenz JA, Khan QJ, Gómez HL, Prat A, et al. Pathological Response and Survival in Triple-Negative Breast Cancer Following Neoadjuvant Carboplatin plus Docetaxel.Clin Cancer Res. 2018;24:5820–9. [DOI] [PubMed] [PMC]
Sella T, Yam ENG, Levanon K, Rotenberg TS, Gadot M, Kuchuk I, et al. Evaluation of tolerability and efficacy of incorporating carboplatin in neoadjuvant anthracycline and taxane based therapy in a BRCA1 enriched triple-negative breast cancer cohort.Breast. 2018;40:141–6. [DOI] [PubMed]
Zhang J, Yao L, Liu Y, Ouyang T, Li J, Wang T, et al. Impact of the addition of carboplatin to anthracycline-taxane-based neoadjuvant chemotherapy on survival in BRCA1/2-mutated triple-negative breast cancer.Int J Cancer. 2021;148:941–9. [DOI] [PubMed]
Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA, et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer.Gynecol Oncol. 2011;121:353–7. [DOI] [PubMed]
Petrillo M, Marchetti C, De Leo R, Musella A, Capoluongo E, Paris I, et al. BRCA mutational status, initial disease presentation, and clinical outcome in high-grade serous advanced ovarian cancer: a multicenter study.Am J Obstet Gynecol. 2017;217:334.e1–9. [DOI] [PubMed]
Lakhani SR, Manek S, Penault-Llorca F, Flanagan A, Arnout L, Merrett S, et al. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers.Clin Cancer Res. 2004;10:2473–81. [DOI] [PubMed]
Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al.; Consortium of Investigators of Modifiers of BRCA1/2. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).Cancer Epidemiol Biomarkers Prev. 2012;21:134–47. [DOI] [PubMed] [PMC]
Nguyen L, Martens JWM, Van Hoeck A, Cuppen E. Pan-cancer landscape of homologous recombination deficiency.Nat Commun. 2020;11:5584. [DOI] [PubMed] [PMC]
LaFargue CJ, Handley KF, Fleming ND, Nick AM, Chelariu-Raicu A, Fellman B, et al. Clinical analysis of pathologic complete responders in advanced-stage ovarian cancer.Gynecol Oncol. 2022;165:82–9. [DOI] [PubMed] [PMC]
Sokolenko AP, Savonevich EL, Ivantsov AO, Raskin GA, Kuligina ES, Gorodnova TV, et al. Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers.Cancer Lett. 2017;397:127–32. [DOI] [PubMed]
Sokolenko A, Preobrazhenskaya E, Marchetti C, Piermattei A, Zagrebin F, Kuligina E, et al. Origin of Residual Tumor Masses in BRCA1/2-Driven Ovarian Carcinomas Treated by Neoadjuvant Chemotherapy: Selection of Preexisting BRCA1/2-Proficient Tumor Cells but Not the Gain of Second ORF-Restoring Mutation.Pathobiology. 2024;91:108–13. [DOI] [PubMed]
Martins FC, De S, Almendro V, Gönen M, Park SY, Blum JL, et al. Evolutionary pathways in BRCA1-associated breast tumors.Cancer Discov. 2012;2:503–11. [DOI] [PubMed] [PMC]
Prakash R, Zhang Y, Feng W, Jasin M. Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins.Cold Spring Harb Perspect Biol. 2015;7:a016600. [DOI] [PubMed] [PMC]
Chabalier C, Lamare C, Racca C, Privat M, Valette A, Larminat F. BRCA1 downregulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistance.Cell Cycle. 2006;5:1001–7. [DOI] [PubMed]
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;384:164–72.Erratum in: Lancet. 2019;393:986. [DOI] [PubMed]
Huang M, O’Shaughnessy J, Zhao J, Haiderali A, Cortés J, Ramsey SD, et al. Association of Pathologic Complete Response with Long-Term Survival Outcomes in Triple-Negative Breast Cancer: A Meta-Analysis.Cancer Res. 2020;80:5427–34. [DOI] [PubMed]
Byrski T, Huzarski T, Dent R, Marczyk E, Jasiowka M, Gronwald J, et al. Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients.Breast Cancer Res Treat. 2014;147:401–5. [DOI] [PubMed]
Moiseyenko VM, Dolmatov GD, Moiseyenko FV, Ivantsov AO, Volkov NM, Chubenko VA, et al. High efficacy of cisplatin neoadjuvant therapy in a prospective series of patients carrying BRCA1 germ-line mutation.Med Oncol. 2015;32:89. [DOI] [PubMed]
Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.Nat Med. 2018;24:628–37. [DOI] [PubMed] [PMC]
Zhou C, Huang P, Liu J. The carboxyl-terminal of BRCA1 is required for subnuclear assembly of RAD51 after treatment with cisplatin but not ionizing radiation in human breast and ovarian cancer cells.Biochem Biophys Res Commun. 2005;336:952–60. [DOI] [PubMed]
Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AOH, Zander SAL, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs.Proc Natl Acad Sci U S A. 2008;105:17079–84. [DOI] [PubMed] [PMC]
Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, et al. Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer.Clin Cancer Res. 2016;22:3764–73. [DOI] [PubMed] [PMC]
Telli ML, Hellyer J, Audeh W, Jensen KC, Bose S, Timms KM, et al. Homologous recombination deficiency (HRD) status predicts response to standard neoadjuvant chemotherapy in patients with triple-negative or BRCA1/2 mutation-associated breast cancer.Breast Cancer Res Treat. 2018;168:625–30. [DOI] [PubMed]
Tung N, Arun B, Hacker MR, Hofstatter E, Toppmeyer DL, Isakoff SJ, et al. TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial).J Clin Oncol. 2020;38:1539–48. [DOI] [PubMed]
