Skip to main content

Advertisement

SpringerLink
Log in

Role of Platinums in Triple-Negative Breast Cancer

  • Breast Cancer (AS Zimmer, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Platinum compounds are used in the treatment of various types of cancer. Here, we review the current role of cisplatin and carboplatin in the treatment of early stage and advanced triple-negative breast cancer (TNBC), and the use of biomarkers in predicting response to platinum therapy.

Recent Findings

Addition of carboplatin to a neoadjuvant chemotherapy regimen can result in improvement in the pathological complete response rates. The long-term benefit of the addition of carboplatin to standard chemotherapy regimens remains unproven. Single-agent platinum is an option in the treatment of advanced breast cancer. BRCA1/2 mutations predicted benefit from platinums in advanced, but not early stage breast cancer. There are yet no biomarkers to predict response to platinum in sporadic TNBC.

Summary

Platinum compounds are an option in the treatment of TNBC. Identification of biomarkers to select tumors most likely to derive benefit from these agents is still needed. Ongoing trials are exploring the role of platinum in the adjuvant setting and in combination with other agents, including immune checkpoint inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Bardal SK, Waechter JE, Martin, DS. Applied pharmacology. Elsevier/Saunders. 2011

  2. Harrap KR. Preclinical studies identifying carboplatin as a viable cisplatin alternative. Cancer Treat Rev. 1985;12(Suppl A):21–33. https://doi.org/10.1016/0305-7372(85)90015-5.

    Article  CAS  PubMed  Google Scholar 

  3. Rose WC, Schurig JE. Preclinical antitumor and toxicology profile of carboplatin. Cancer Treat Rev. 1985;12(Suppl A):1–19. https://doi.org/10.1016/0305-7372(85)90014-3.

    Article  CAS  PubMed  Google Scholar 

  4. Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer. 1998;34(10):1522–34. https://doi.org/10.1016/s0959-8049(98)00224-x.

    Article  CAS  PubMed  Google Scholar 

  5. Calvert AH, Harland SJ, Newell DR, Siddik ZH, Jones AC, McElwain TJ, et al. Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II. Cancer Chemoth Pharmacol. 1982;9(3):140–7. https://doi.org/10.1007/BF00257742.

    Article  CAS  Google Scholar 

  6. 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 Can Res Treat. 2014;147:401–5.

  7. Turner N, Tutt A, Ashworth A. Hallmarks of “BRCAness” in sporadic cancer. Nat Rev Cancer. 2004;4(10):814–9.

    Article  CAS  Google Scholar 

  8. • 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 This trial level analysis was conducted to assess whether pathological complete response could be used as a surrogate endpoint for EFS or OS.

    Article  Google Scholar 

  9. Yee D, DeMichele AM, Yau C, Isaacs C, Symmans WF, Albain KS, et al. Association of event-free and distant recurrence–free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. Published online July 23, 2020. doi:https://doi.org/10.1001/jamaoncol.2020.2535

  10. Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, et al. Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 2020;6(5):1–9.

    Article  Google Scholar 

  11. Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382:810–21.

    Article  CAS  Google Scholar 

  12. Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30(8):1279. https://doi.org/10.1093/annonc/mdz158.

  13. Rugo HS, Olopade OI, DeMichele A, Yau C, van’t Veer LJ, et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016;375(1):23–34.

  14. •• 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 This phase III trial examined the impact of adding carboplatin and/or bevacizumab in the pCR rate and long-term outcomes for patients with early stage TNBC.

    Article  CAS  Google Scholar 

  15. Golshan M, Cirrincione CT, Sikov WM, Berry DA, Jasinski S, Weisberg TF, et al. Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance). Ann Surg. 2015;262(3):434–9.

  16. Sikov WM, Polley MY, Twohy E, Perou CM, Singh B, Berry DA et al. CALGB (alliance) 40603: long-term outcomes (LTOs) after neoadjuvant chemotherapy (NACT) +/- carboplatin (Cb) and bevacizumab (Bev) in triple-negative breast cancer (TNBC). J Clin Oncol. 2019; 37, no. 15_suppl, 591-591.

  17. Katherine A Hoadley, Bradford C. Powell, Dona Kanavy, David Marron, Lisle E. Mose, Terry Hyslop, Donald A. Berry, Olwen Hahn, Sara M. Tolaney, William M. Sikov, Charles M. Perou, Lisa A. Carey. Mutational analysis of triple-negative breast cancer (TNBC): CALGB 40603 (Alliance) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-03

  18. 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 randomized phase 2 trial. Lancet Oncol. 2014;15(7):747–56.

    Article  Google Scholar 

  19. Hahnen E, Lederer B, Hauke J, Loibl S, Krober S, Scheeweiss 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(10):1378–85.

    Article  Google Scholar 

  20. 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.

  21. Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, 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. 2014;33:983–91.

    Article  Google Scholar 

  22. 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 randomized, phase 3 trial. Lancet Oncol. 2018;19(4):497–509. https://doi.org/10.1016/S1470-2045(18)30111-6.

    Article  CAS  PubMed  Google Scholar 

  23. Telli M, Metzger O, Timms K, Evans B, Vogel D, et al. Evaluation of homologous recombination deficiency (HRD) status with pathological response to carboplatin +/- veliparib in BrighTNess, a randomized phase 3 study in early stage TNBC. J Clin Oncol. 2018;15:519–9.

  24. Gianni L, Huang C, Egle D, et al. Pathologic complete response to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study. 2019 San Antonio Breast Cancer Symposium. Abstract GS3-04. Presented December 12, 2019.

  25. Sharma P, Lopez-Tarruella S, Garcia-Saenz JA, Khan QJ, Gomez HL, Prat A, et al. Pathological response and survival in triple-negative breast cancer following neoadjuvant carboplatin plus docetaxel. Clin Cancer Res. 2018;24(8):1845–52.

    Article  Google Scholar 

  26. Sharma P, Kimler BF, O’Dea A, Nye LE, Wang YY, Yoder R, et al. Results of randomized phase II trial of neoadjuvant carboplatin plus docetaxel or carboplatin plus paclitaxel followed by AC in stage I-III triple negative breast cancer. J Clin Oncol. 2019;37(15_suppl):516.

    Article  Google Scholar 

  27. Tung N, Arun B, Hacker MR, Hofstatter E, Toppmeyer DL, 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 May 10;38(14):1539–48.

    Article  CAS  Google Scholar 

  28. Tung NM, Boughey JC, Pierce LJ, Robson ME, Bedrosian I, Dietz JR, et al. Management of hereditary breast cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline. J Clin Oncol. 2020;38:2080–106.

  29. Burstein HJ, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P, et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International consensus Guidelines for the primary therapy of early breast cancer 2019. Ann Oncol. 2019;30(10):1541–57.

  30. Isakoff SJ, Mayer E, He L, Traina TA, Carey LA, Krag KJ, et al. TBCRC009: a multicenter phase II clinical trial of platinum monotherapy with biomarker assessment in metastatic triple-negative breast cancer. J Clin Oncol. 2015;33(17):1902–9.

    Article  CAS  Google Scholar 

  31. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.

  32. •• 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(5):628–37 This phase III randomized patients with metastatic breast cancer to carboplatin or docetaxel in the first-line setting.

    Article  CAS  Google Scholar 

  33. Sharma P, Rodler E, Barlow WE, Gralow J, Huggins-Puhalla SL, et al. Results of a phase II randmozined trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416). Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 1001-1001

  34. O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, et al. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014;32(34):3840–7.

    Article  Google Scholar 

  35. Yardley DA, Coleman R, Conte P, Cortes J, Brufsky A, Shtivelband M, et al. Nab-paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial. Ann Oncol. 2018;29:1763–70.

  36. Lander EM, Lehmann BD, Shah PD, Dees EC, Ballinger TJ, et al. A phase II trial of atezolizumab (anti-PD-L1) with carboplatin in patients with metastatic triple-negative breast cancer (mTNBC). DOI: 10.1200/JCO.2020.38.15_suppl.TPS1112 Journal of Clinical Oncology 38, no. 15.

  37. Vidula N, Nanda R, Miller K, Abramson V, Pohlmann P, et al. Abstract OT2-04-05: pembrolizumab in combination with carboplatin versus carboplatin alone in breast cancer patients with chest wall disease: Translational Breast Cancer Research Consortium (TBCRC) 44 trial. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-04-05.

  38. Telli M, Timms KM, Reid J, Hennessy B, Mills GB, 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(15):3764–73.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave YC-1275, Boston, MA, 02215, USA

    Filipa Lynce

  2. Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, Building B, First Floor, 5255 Loughboro Rd, NW, Washington, DC, 20016, USA

    Raquel Nunes

Authors
  1. Filipa Lynce
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raquel Nunes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Filipa Lynce.

Ethics declarations

Conflict of Interest

Filipa Lynce has received research funding from Bristol-Myers Squibb, Pfizer, Tesaro, Immunomedics, Calithera Biosciences, Regeneron, and Inivata Ltd.; has received compensation from Bristol-Myers Squibb and Pfizer for service as a consultant; and has received non-financial support from Jounce Therapeutics. Raquel Nunes declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Breast Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lynce, F., Nunes, R. Role of Platinums in Triple-Negative Breast Cancer. Curr Oncol Rep 23, 50 (2021). https://doi.org/10.1007/s11912-021-01041-x

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11912-021-01041-x

Keywords

Search

Navigation