Table Info

Table 1.

Surrogate definitions of intrinsic subtypes of BC [10, 12]

Intrinsic subtype	Immunohistochemical phenotype	Frequency (%)
Luminal A-like	High ER and PgR; HER2-negative; low proliferation rates; typically low grade; low Ki-67 index	60–70%
Luminal B-like HER2-negative	ER-positive, but ER and PgR expression lower than in luminal A-like; HER2-negative; higher grade; high Ki-67 index	10–20%
Luminal B-like HER2-positive	ER-positive, but ER and PgR expression lower than in luminal A-like; HER2-positive; higher grade; high Ki-67 index	Both 13–15%
HER2-positive (non-luminal)	HER2-positive; ER and PgR absent; high grade; high Ki-67 index	Both 13–15%
TNBC	ER and PgR absent, HER2-negative; higher grade; high Ki-67 index	10–15%

ER: estrogen receptor; HER2: human epidermal growth factor receptor 2; PgR: progesterone receptor; BC: breast cancer; TNBC: triple-negative breast cancer

Declarations

Author contributions

VP and SC: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. CA: Visualization, Conceptualization, Writing—review & editing. TB: Data curation, Writing—review & editing. RTdS: Conceptualization, Writing—review & editing. ST, LAR, GNC, HLP, CP, and Leila C: Writing—review & editing. Luís C: Visualization, Conceptualization, Writing—review & editing.

Conflicts of interest

The authors declare no conflicts of interest.

Ethical approval

This study was approved by the ethics committee of COMISSÃO DE ÉTICA DO CAML.

Consent to participate

The consent to participate has been waived by the IRB of COMISSÃO DE ÉTICA DO CAML given the retrospective nature of this study.

Consent to publication

Not applicable.

Availability of data and materials

The raw data supporting the conclusions of this manuscript will be made available by the authors (Vanessa Patel, vanessacpatel@gmail.com) , without undue reservation, to any qualified researcher.

Funding

Not applicable.

Copyright

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. [DOI] [PubMed]

Programa Nacional para as doenças oncológicas 2017 [Internet]. Lisboa: Direção-Geral da Saúde; c2024 [cited 2023 Nov 10]. Available from: https://www.iccp-portal.org/system/files/plans/DGS_PNDO2017_V10.pdf

Wang R, Zhu Y, Liu X, Liao X, He J, Niu L. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer. 2019;19:1091. [DOI] [PubMed] [PMC]

Cardoso F, Harbeck N, Fallowfield L, Kyriakides S, Senkus E. Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23:vii11–9. [DOI] [PubMed]

Lindman H, Wiklund F, Andersen KK. Long-term treatment patterns and survival in metastatic breast cancer by intrinsic subtypes–an observational cohort study in Sweden. BMC Cancer. 2022;22:1006. [DOI] [PubMed] [PMC]

Guarneri V, Conte PF. The curability of breast cancer and the treatment of advanced disease. Eur J Nucl Med Mol Imaging. 2004;31:S149–61. [DOI]

Merloni F, Palleschi M, Casadei C, Romeo A, Curcio A, Casadei R, et al. Oligometastatic breast cancer and metastasis-directed treatment: an aggressive multimodal approach to reach the cure. Ther Adv Med Oncol. 2023;15:175883592311614. [DOI] [PubMed] [PMC]

Barberi V, Pietragalla A, Franceschini G, Marazzi F, Paris I, Cognetti F, et al. Oligometastatic breast cancer: how to manage it? J Pers Med. 2021;11:532. [DOI] [PubMed] [PMC]

Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–85. [DOI] [PubMed]

10.

Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer. Nat Rev Dis Primers. 2019;5:66. [DOI] [PubMed]

11.

Xiao W, Zheng S, Yang A, Zhang X, Zou Y, Tang H, et al. Breast cancer subtypes and the risk of distant metastasis at initial diagnosis: a population-based study. Cancer Manag Res. 2018;10:5329–38. [DOI] [PubMed] [PMC]

12.

Loibl S, André F, Bachelot T, Barrios CH, Bergh J, Burstein HJ, et al.; ESMO Guidelines Committee. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35:159–82. [DOI] [PubMed]

13.

Dawood SS, Kristine B, Hortobagyi GN, Giordano SH. Prognosis of women with stage IV breast cancer by HER2 status and trastuzumab treatment: an institutional based review. J Clin Oncol. 2008;26:1018. [DOI]

14.

Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, et al.; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy in advanced triple-negative breast bancer. N Engl J Med. 2022;387:217–26. [DOI] [PubMed]

15.

Incorvaia L, Fanale D, Bono M, Calò V, Fiorino A, Brando C, et al. BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients. Ther Adv Med Oncol. 2020;12:1758835920975326. [DOI] [PubMed] [PMC]

16.

Kurian AW, Gong GD, John EM, Miron A, Felberg A, Phipps AI, et al. Performance of prediction models for BRCA mutation carriage in three racial/ethnic groups: findings from the Northern California Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2009;18:1084–91. [DOI] [PubMed] [PMC]

17.

Sun W, Wu Y, Ma F, Fan J, Qiao Y. Efficacy of PARP inhibitor, platinum, and immunotherapy in BRCA-mutated HER2-negative breast cancer patients: a systematic review and network meta-analysis. J Clin Med. 2023;12:1588. [DOI] [PubMed] [PMC]

18.

Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, 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;30:558–66. [DOI] [PubMed] [PMC]

19.

Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379:753–63. [DOI] [PubMed] [PMC]

20.

Blackford AN, Jackson SP. ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response. Mol Cell. 2017;66:801–17. [DOI] [PubMed]

21.

Li X, Heyer WD. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 2008;18:99–113. [DOI] [PubMed] [PMC]

22.

Elbakry A, Löbrich M. Homologous recombination subpathways: a tangle to resolve. Front Genet. 2021;12:723847. [DOI] [PubMed] [PMC]

23.

Robinson DR, Wu YM, Lonigro RJ, Vats P, Cobain E, Everett J, et al. Integrative clinical genomics of metastatic cancer. Nature. 2017;548:297–303. [DOI] [PubMed] [PMC]

24.

Shao C, Wan J, Lam FC, Tang H, Marley AR, Song Y, et al. A comprehensive literature review and meta‐analysis of the prevalence of pan‐cancer BRCA mutations, homologous recombination repair gene mutations, and homologous recombination deficiencies. Environ Mol Mutagen. 2022;63:308–16. [DOI] [PubMed]

25.

Voutsadakis IA, Stravodimou A. Homologous recombination defects and mutations in DNA damage response (DDR) genes besides BRCA₁ and BRCA₂ as breast cancer biomarkers for PARP inhibitors and other DDR targeting therapies. Anticancer Res. 2023;43:967–81. [DOI] [PubMed]

26.

Li Q, Jiang B, Guo J, Shao H, Del Priore IS, Chang Q, et al. INK4 tumor suppressor proteins mediate resistance to CDK4/6 kinase inhibitors. Cancer Discov. 2022;12:356–71. [DOI] [PubMed] [PMC]

27.

Hopkins JL, Lan L, Zou L. DNA repair defects in cancer and therapeutic opportunities. Genes Dev. 2022;36:278–93. [DOI] [PubMed] [PMC]

28.

Anurag M, Punturi N, Hoog J, Bainbridge MN, Ellis MJ, Haricharan S. Comprehensive profiling of DNA repair defects in breast cancer identifies a novel class of endocrine therapy resistance drivers. Clin Cancer Res. 2018;24:4887–99. [DOI] [PubMed] [PMC]

29.

Davies H, Glodzik D, Morganella S, Yates LR, Staaf J, Zou X, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017;23:517–25. [DOI] [PubMed] [PMC]

30.

Moore GM, Powell SN, Higginson DS, Khan AJ. Examining the prevalence of homologous recombination repair defects in ER+ breast cancers. Breast Cancer Res Treat. 2022;192:649–53. [DOI] [PubMed]

31.

Gou R, Dong H, Lin B. Application and reflection of genomic scar assays in evaluating the efficacy of platinum salts and PARP inhibitors in cancer therapy. Life Sci. 2020;261:118434. [DOI] [PubMed]

32.

Timms KM, Abkevich V, Hughes E, Neff C, Reid J, Morris B, et al. Association of BRCA1/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes. Breast Cancer Res. 2014;16:475. [DOI] [PubMed] [PMC]

33.

Ford L, Wolford JE, Brown SM, Randall LM. A profile on the FoundationFocus CDxBRCA tests. Expert Rev Mol Diagn. 2020;20:285–92. [DOI] [PubMed]

34.

Westphalen CB, Fine AD, André F, Ganesan S, Heinemann V, Rouleau E, et al. Pan-cancer analysis of homologous recombination repair–associated gene alterations and genome-wide loss-of-heterozygosity score. Clin Cancer Res. 2022;28:1412–21. [DOI] [PubMed] [PMC]

35.

Helleday T. The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol Oncol. 2011;5:387–93. [DOI] [PubMed] [PMC]

36.

Castroviejo‐Bermejo M, Cruz C, Llop‐Guevara A, Gutiérrez‐Enríquez S, Ducy M, Ibrahim YH, et al. A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation. EMBO Mol Med. 2018;10:e9172. [DOI] [PubMed] [PMC]

37.

Cruz C, Castroviejo-Bermejo M, Gutiérrez-Enríquez S, Llop-Guevara A, Ibrahim YH, Gris-Oliver A, et al. RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer. Ann Oncol. 2018;29:1203–10. [DOI] [PubMed] [PMC]

38.

Serra V, Wang AT, Castroviejo-Bermejo M, Polanska UM, Palafox M, Herencia-Ropero A, et al. Identification of a molecularly-defined subset of breast and ovarian cancer models that respond to WEE1 or ATR inhibition, overcoming PARP inhibitor resistance. Clin Cancer Res. 2022;28:4536–50. [DOI] [PubMed] [PMC]

39.

Vicente R, Alpuim Costa D, Vitorino M, Mendes AD, Santos C, Fontes-Sousa M. Mutation patterns in Portuguese families with hereditary breast and ovarian cancer syndrome. Cancers (Basel). 2022;14:4717. [DOI] [PubMed] [PMC]

40.

Ferla R, Calò V, Cascio S, Rinaldi G, Badalamenti G, Carreca I, et al. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007;18:vi93–8. [DOI] [PubMed]

41.

Peixoto A, Santos C, Pinto P, Pinheiro M, Rocha P, Pinto C, et al. The role of targeted BRCA1/BRCA2 mutation analysis in hereditary breast/ovarian cancer families of Portuguese ancestry. Clin Genet. 2015;88:41–8. [DOI] [PubMed]

42.

Palmero EI, Carraro DM, Alemar B, Moreira MAM, Ribeiro-dos-Santos Â, Abe-Sandes K, et al. The germline mutational landscape of BRCA1 and BRCA2 in Brazil. Sci Rep. 2018;8:9188. [DOI] [PubMed] [PMC]

43.

Torrisi R, Zuradelli M, Agostinetto E, Masci G, Losurdo A, De Sanctis R, et al. Platinum salts in the treatment of BRCA-associated breast cancer: a true targeted chemotherapy? Crit Rev Oncol Hematol. 2019;135:66–75. [DOI] [PubMed]

44.

Tassone P, Tagliaferri P, Perricelli A, Blotta S, Quaresima B, Martelli ML, et al. BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. Br J Cancer. 2003;88:1285–91. [DOI] [PubMed] [PMC]

45.

Quinn JE, Kennedy RD, Mullan PB, Gilmore PM, Carty M, Johnston PG, et al. BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res. 2003;63:6221–8. [PubMed]

46.

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]

47.

Isakoff SJ, Mayer EL, 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;33:1902–9. [DOI] [PubMed] [PMC]

48.

Keung M, Wu Y, Vadgama J. PARP inhibitors as a therapeutic agent for homologous recombination deficiency in breast cancers. J Clin Med. 2019;8:435. [DOI] [PubMed] [PMC]

49.

Huang D, Kraus WL. The expanding universe of PARP1-mediated molecular and therapeutic mechanisms. Mol Cell. 2022;82:2315–34. [DOI] [PubMed] [PMC]

50.

Faraoni I, Graziani G. Role of BRCA mutations in cancer treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. Cancers (Basel). 2018;10:487. [DOI] [PubMed] [PMC]

51.

Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017;355:1152–8. [DOI] [PubMed] [PMC]

52.

Lord CJ, Ashworth A. Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat Med. 2013;19:1381–8. [DOI] [PubMed]

53.

Spriggs DR, Longo DL. PARP inhibitors in ovarian cancer treatment. N Engl J Med. 2016;375:2197–8. [DOI] [PubMed]

54.

Farmer H, McCabe N, Lord CJ, Tutt ANJ, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21. [DOI] [PubMed]

55.

Surjana D, Halliday GM, Damian DL. Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. J Nucleic Acids. 2010;2010:157591. [DOI] [PubMed] [PMC]

56.

Tung N, Garber JE. PARP inhibition in breast cancer: progress made and future hopes. NPJ Breast Cancer. 2022;8:47. [DOI] [PubMed] [PMC]

57.

Murai J, Huang SN, Das BB, Renaud A, Zhang Y, Doroshow JH, et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 2012;72:5588–99. [DOI] [PubMed] [PMC]

58.

Mateo J, Lord CJ, Serra V, Tutt A, Balmaña J, Castroviejo-Bermejo M, et al. A decade of clinical development of PARP inhibitors in perspective. Ann Oncol. 2019;30:1437–47. [DOI] [PubMed] [PMC]

59.

Rose M, Burgess JT, O’Byrne K, Richard DJ, Bolderson E. PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance. Front Cell Dev Biol. 2020;8:564601. [DOI] [PubMed] [PMC]

60.

Murthy P, Muggia F. PARP inhibitors: clinical development, emerging differences, and the current therapeutic issues. Cancer Drug Resist. 2019;2:665–79. [DOI] [PubMed] [PMC]

61.

Godon C, Cordelieres FP, Biard D, Giocanti N, Megnin-Chanet F, Hall J, et al. PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility. Nucleic Acids Res. 2008;36:4454–64. [DOI] [PubMed] [PMC]

62.

Konecny GE, Kristeleit RS. PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions. Br J Cancer. 2016;115:1157–73. [DOI] [PubMed] [PMC]

63.

Dziadkowiec KN, Gąsiorowska E, Nowak-Markwitz E, Jankowska A. PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting. Prz Menopauzalny. 2016;4:215–9. [DOI] [PubMed] [PMC]

64.

Ray Chaudhuri A, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol. 2017;18:610–21. [DOI] [PubMed] [PMC]

65.

Min A, Im SA, Yoon YK, Song SH, Nam HJ, Hur HS, et al. RAD51C-deficient cancer cells are highly sensitive to the PARP inhibitor olaparib. Mol Cancer Ther. 2013;12:865–77. [DOI] [PubMed]

66.

Leithe E, Rivedal E. Epidermal growth factor regulates ubiquitination, internalization and proteasome-dependent degradation of connexin43. J Cell Sci. 2004;117:1211–20. Erratum in: J Cell Sci. 2004;117:1613. [DOI] [PubMed]

67.

Robson ME, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, et al. OlympiAD extended follow-up for overall survival and safety: olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Eur J Cancer. 2023;184:39–47. [DOI] [PubMed] [PMC]

68.

Domchek SM, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol. 2020;21:1155–64. [DOI] [PubMed]

69.

Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat. 2018;167:671–86. [DOI] [PubMed] [PMC]

70.

Diéras V, Han HS, Kaufman B, Wildiers H, Friedlander M, Ayoub JP, et al. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21:1269–82. [DOI] [PubMed]

71.

Vinayak S, Tolaney SM, Schwartzberg LS, Mita MM, McCann GAL, Tan AR, et al. TOPACIO/Keynote-162: niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial. J Clin Oncol. 2018;36:1011. [DOI]

72.

Heilig CE, Hübschmann D, Kopp HG, Metzeler KH, Richter S, Hermes B, et al. Randomized phase II study of trabectedin/olaparib compared to physician’s choice in subjects with previously treated advanced or recurrent solid tumors harboring dna repair deficiencies. Ann Oncol. 2019;30:v795–6. [DOI]

73.

Poveda A, Lopez-Reig R, Oaknin A, Redondo A, Rubio MJ, Guerra E, et al. Phase 2 trial (POLA Study) of lurbinectedin plus olaparib in patients with advanced solid tumors: results of efficacy, tolerability, and the translational study. Cancers (Basel). 2022;14:915. [DOI] [PubMed] [PMC]

74.

Lynce F, Graham N, Kochupurakkal BS, Nguyen H, Poorvu PD, Attaya V, et al. Abstract CT188: a phase Ib study of sapacitabine (sapa) and olaparib (ola) in patients (pts) with BRCA1/2-mutated (BRCA1/2m) metastatic breast cancer (MBC). Cancer Res. 2023;83:CT188. [DOI]

75.

Chabanon RM, Pedrero M, Lefebvre C, Marabelle A, Soria JC, Postel-Vinay S. Mutational landscape and sensitivity to immune checkpoint blockers. Clin Cancer Res. 2016;22:4309–21. [DOI] [PubMed]

76.

Jiao S, Xia W, Yamaguchi H, Wei Y, Chen MK, Hsu JM, et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res. 2017;23:3711–20. [DOI] [PubMed] [PMC]

77.

Wagner L. Profile of veliparib and its potential in the treatment of solid tumors. Onco Targets Ther. 2015;8:1931–9. [DOI] [PubMed] [PMC]

78.

Chen J, Shen X, Pardue S, Meram AT, Rajendran S, Ghali GE, et al. The Ataxia telangiectasia-mutated and Rad3-related protein kinase regulates cellular hydrogen sulfide concentrations. DNA Repair (Amst). 2019;73:55–63. [DOI] [PubMed] [PMC]

79.

Roulston A, Zimmermann M, Papp R, Skeldon A, Pellerin C, Dumas-Bérube É, et al. RP-3500: a novel, potent, and selective ATR inhibitor that is effective in preclinical models as a monotherapy and in combination with PARP inhibitors. Mol Cancer Ther. 2022;21:245–56. [DOI] [PubMed] [PMC]

80.

Wilson Z, Odedra R, Wallez Y, Wijnhoven PWG, Hughes AM, Gerrard J, et al. ATR inhibitor AZD6738 (ceralasertib) exerts antitumor activity as a monotherapy and in combination with chemotherapy and the PARP inhibitor olaparib. Cancer Res. 2022;82:1140–52. [DOI] [PubMed] [PMC]

81.

Middleton MR, Dean E, Evans TRJ, Shapiro GI, Pollard J, Hendriks BS, et al. Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours. Br J Cancer. 2021;125:510–9. [DOI] [PubMed] [PMC]

82.

Telli ML, Tolaney SM, Shapiro GI, Middleton M, Lord SR, Arkenau HT, et al. Phase 1b study of berzosertib and cisplatin in patients with advanced triple-negative breast cancer. NPJ Breast Cancer. 2022;8:45. [DOI] [PubMed] [PMC]

83.

Gatei M, Sloper K, Sörensen C, Syljuäsen R, Falck J, Hobson K, et al. Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation. J Biol Chem. 2003;278:14806–11. [DOI] [PubMed]

84.

Gatti-Mays ME, Karzai FH, Soltani SN, Zimmer A, Green JE, Lee MJ, et al. A phase II single arm pilot study of the CHK1 inhibitor prexasertib (LY2606368) in BRCA wild-type, advanced triple-negative breast cancer. Oncologist. 2020;25:1013-e1824. [DOI] [PubMed] [PMC]

85.

Qu Y, Qin S, Yang Z, Li Z, Liang Q, Long T, et al. Targeting the DNA repair pathway for breast cancer therapy: beyond the molecular subtypes. Biomed Pharmacother. 2023;169:115877. [DOI] [PubMed]

86.

Do KT, Kochupurakkal B, Kelland S, de Jonge A, Hedglin J, Powers A, et al. Phase 1 combination study of the CHK1 inhibitor prexasertib and the PARP inhibitor olaparib in high-grade serous ovarian cancer and other solid tumors. Clin Cancer Res. 2021;27:4710–6. [DOI] [PubMed]

87.

Ghelli Luserna di Rorà A, Cerchione C, Martinelli G, Simonetti G. A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target. J Hematol Oncol. 2020;13:126. [DOI] [PubMed] [PMC]

88.

Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, et al. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021;397:281–92. [DOI] [PubMed] [PMC]

89.

Moore KN, Chambers SK, Hamilton EP, Chen LM, Oza AM, Ghamande SA, et al. Adavosertib with chemotherapy in patients with primary platinum-resistant ovarian, fallopian tube, or peritoneal cancer: an open-label, four-arm, phase II study. Clin Cancer Res. 2022;28:36–44. [DOI] [PubMed]

90.

Fang Y, McGrail DJ, Sun C, Labrie M, Chen X, Zhang D, et al. Sequential therapy with PARP and WEE1 inhibitors minimizes toxicity while maintaining efficacy. Cancer Cell. 2019;35:851–67.e7. [DOI] [PubMed] [PMC]

91.

Miller RE, Leary A, Scott CL, Serra V, Lord CJ, Bowtell D, et al. ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer. Ann Oncol. 2020;31:1606–22. [DOI] [PubMed]

92.

Hodgson DR, Dougherty BA, Lai Z, Fielding A, Grinsted L, Spencer S, et al. Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Br J Cancer. 2018;119:1401–9. [DOI] [PubMed] [PMC]

93.

Menezes M, Raheem F, Mina L, Ernst B, Batalini F. PARP inhibitors for breast cancer: germline BRCA1/2 and beyond. Cancers (Basel). 2022;14:4332. [DOI] [PubMed] [PMC]

94.

Yoon JK, Ahn J, Kim S, Kim HP, Kang JK, Bang D, et al. Efficacy of olaparib in treatment-refractory, metastatic breast cancer with uncommon somatic BRCA mutations detected in circulating tumor DNA. Cancer Res Treat. 2023;55:1048–52. [DOI] [PubMed] [PMC]

95.

Mohyuddin GR, Aziz M, Britt A, Wade L, Sun W, Baranda J, et al. Similar response rates and survival with PARP inhibitors for patients with solid tumors harboring somatic versus germline BRCA mutations: a Meta-analysis and systematic review. BMC Cancer. 2020;20:507. [DOI] [PubMed] [PMC]