Maintenance therapy with talazoparib in a patient with metastatic triple-negative breast cancer after complete clinical response to 1 line of drug therapy

Triple negative breast cancer (TNBC) accounts for about 15 % of all diagnosed breast cancer cases and is an extremely aggressive disease with a high incidence of recurrence and metastases. Due to the molecular and biological features of this type of tumor, the currently available therapeutic options for the treatment of patients with advanced disease are extremely limited and include mainly the use of chemotherapy – classical cytostatic drugs. In recent years, great efforts of the scientific oncology community have been focused on the identification of specific targets for TNBC, which has additionally brought immuno-oncology drugs, PARP inhibitors and antibody-drug conjugates to the clinicians’ arsenal. Thanks to significant advances in the field of molecular genetics, it has been established that in triple negative subtype of breast cancer in almost 20 % of cases the presence of germinal mutations in BRCA1/2 genes is noted, therefore, testing patients for the presence of these aberrations is now an obligatory stage of diagnosis, starting from the earliest stages of the cancer process. Despite the fact that metastatic TNBC is generally considered an incurable disease, there are single reports in the literature describing cases of achieving a complete clinical response during drug treatment. Unfortunately, due to the rarity of such cases, the further management of patients remains largely uncertain. In this case report, we demonstrate our own positive experience with the PARP inhibitor talazoparib as maintenance therapy in a patient with advanced triple-negative breast cancer and a mutation in the BRCA gene after achieving a complete clinical response to 1 line of platinumcontaining therapy. This observation adds to the existing data and emphasizes the need for PARP inhibitors in the treatment of TNBC, and confirms the importance of further research in molecular genetics to develop more effective treatment approaches.

1. Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discovery. 2022; 12 (1): 31–46.

2. Petropoulos M. et al. Transcription–replication conflicts underlie sensitivity to PARP inhibitors. Nature. Nature Publishing Group. 2024; 628 (8007): 433–441.

3. Bhamidipati D. et al. PARP inhibitors: enhancing efficacy through rational combinations. Br. J. Cancer. Nature Publishing Group. 2023; 129 (6): 904–916.

4. Jubin T. et al. The PARP family: insights into functional aspects of poly (ADP-ribose) polymerase-1 in cell growth and survival. Cell Prolif. 2016; 49 (4): 421–437.

5. Yamamoto H., Hirasawa A. Homologous Recombination Deficiencies and Hereditary Tumors. Int J. Mol Sci. 2021; 23 (1): 348.

6. Skelin M. et al. The effect of PARP inhibitors in homologous recombination proficient ovarian cancer: meta-analysis. J. Chemother. 2023; 35 (2): 150–157.

7. McNevin C.S. et al. PARP Inhibitors in Advanced Prostate Cancer in Tumors with DNA Damage Signatures. Cancers (Basel). 2022; 14 (19): 4751.

8. Murai J. et al. Differential trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 2012; 72 (21): 5588–5599.

9. Mateo J. et al. A decade of clinical development of PARP inhibitors in perspective. Ann Oncol. 2019; 30 (9): 1437–1447.

10. Dass S. A. et al. Triple Negative Breast Cancer: A Review of Present and Future Diagnostic Modalities. Medicina (Kaunas). 2021; 57 (1): 62.

11. Martínez-Gregorio H. et al. The Evolution of Clinically Aggressive Triple-Negative Breast Cancer Shows a Large Mutational Diversity and Early Metastasis to Lymph Nodes. Cancers (Basel). 2021; 13 (20): 5091.

12. Bolotina L. V. Drug Therapy Strategy for Metastatic Breast Cancer in the Context of Expanding Anti-Tumor Drug Pallet: 2. Voprosy Onkologii. 2024; 70 (2): 248–258. (In Russ.).

13. Obidiro O., Battogtokh G., Akala E. O. Triple Negative Breast Cancer Treatment Options and Limitations: Future Outlook. Pharmaceutics. 2023; 15 (7): 1796.

14. Huppert L. A., Gumusay O., Rugo H. S. Emerging treatment strategies for metastatic triple-negative breast cancer. Ther Adv Med Oncol. 2022; 14: 17588359221086916.

15. Shi M. et al. Efficacy and safety of first-line treatment for metastatic triple-negative breast cancer: A network meta-analysis. Cancer Pathogenesis and Therapy. 2024; 2 (2): 81–90.

16. Alkaabi D. et al. PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression. Int J. Mol. Sci. 2023; 24 (7): 6420.

17. Krasniqi E. et al. Second-line Eribulin in Triple Negative Metastatic Breast Cancer patients. Multicentre Retrospective Study: The TETRIS Trial. Int J. Med. Sci. 2021; 18 (10): 2245–2250.

18. Park W. K. et al. Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations. NPJ Precis Oncol. 2024; 8 (1): 96.

19. Daly G. R. et al. PARP Inhibitors in Breast Cancer: a Short Communication. Curr Oncol Rep. 2024; 26 (2): 103–113.

20. Robson M. et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl. J. Med. 2017; 377 (6): 523–533.

21. Litton J. K. et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl. J. Med. 2018; 379 (8): 753–763.

22. Robson M. E. et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019; 30 (4): 558–566.

23. Litton J. K. et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Annals of Oncology. Elsevier. 2020; 31 (11): 1526–1535.

24. Zhang C. et al. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics. 2022; 12 (5): 2115–2132.

25. Helleday T. The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing up the misunderstandings. Mol Oncol. 2011; 5 (4): 387–393.

26. Rottenberg S. et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD 2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A. 2008; 105 (44): 17079–17084.

27. Caparica R., Lambertini M., Azambuja E. de. How I treat metastatic triple-negative breast cancer. ESMO Open. Elsevier. 2019; 4.

28. Tutt A. et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018; 24 (5): 628–637.

29. Kassam F. et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer. 2009; 9 (1): 29–33.

30. Horimoto Y. et al. Characteristics of metastatic breast cancer patients obtaining a clinical complete response with systemic therapies. European Journal of Cancer. Elsevier. 2020; 138: S 62–S 63.

31. DiSilvestro P. et al. Overall Survival with Maintenance Olaparib at a 7-Year Follow-Up in Patients with Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J. Clin. Oncol. 2023; 41 (3): 609–617.

32. Moore Kathleen et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine. Massachusetts Medical Society. 2018; 379 (26): 2495–2505.