Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: The TNT Trial

Nature Medicine

Volumn 24, Issue 5, 2018, Pages 628-637

  Tutt, Andrew ^a,b   Tovey, Holly ^a   Cheang, Maggie Chon U ^a   Kernaghan, Sarah ^a   Kilburn, Lucy ^a   Gazinska, Patrycja ^b   Owen, Julie ^c   Abraham, Jacinta ^d   Barrett, Sophie ^e   Barrett Lee, Peter ^d   Brown, Robert ^a,f   Chan, Stephen ^g   Dowsett, Mitchell ^a,h   Flanagan, James M ^f   Fox, Lisa ^a   Grigoriadis, Anita ^b   Gutin, Alexander ⁱ   Harper Wynne, Catherine ^j   Hatton, Matthew Q ^k   Hoadley, Katherine A ^l   Parikh, Jyoti ^m   Parker, Peter ^n,o   Perou, Charles M ^l   Roylance, Rebecca ^p   Shah, Vandna ^b   Shaw, Adam ^m   Smith, Ian E ^q   Timms, Kirsten M ⁱ   Wardley, Andrew M ^r   Wilson, Gregory ^s   Gillett, Cheryl ^b,c   Lanchbury, Jerry S ⁱ   Ashworth, Alan ^t   Rahman, Nazneen ^a,q   Harries, Mark ^m   Ellis, Paul ^m   Pinder, Sarah E ^b,c   Bliss, Judith M ^a   more..

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b GUY S HOSPITAL   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d VELINDRE CANCER CENTRE   (United Kingdom)

^e BEATSON WEST OF SCOTLAND CANCER CENTRE   (United Kingdom)

^f IMPERIAL COLLEGE LONDON   (United Kingdom)

^g NOTTINGHAM UNIVERSITY HOSPITALS NHS TRUST   (United Kingdom)

^h ROYAL MARSDEN HOSPITAL   (United Kingdom)

ⁱ Utah   (United States)

^j MAIDSTONE AND TUNBRIDGE WELLS NHS TRUST   (United Kingdom)

^k WESTON PARK HOSPITAL   (United Kingdom)

^l UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^m GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

ⁿ KING'S COLLEGE LONDON   (United Kingdom)

^o THE FRANCIS CRICK INSTITUTE   (United Kingdom)

^p UNIVERSITY COLLEGE LONDON HOSPITALS   (United Kingdom)

^q INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^r UNIVERSITY OF MANCHESTER   (United Kingdom)

^s CHRISTIE HOSPITAL   (United Kingdom)

^t UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BRCA1 PROTEIN; BRCA2 PROTEIN; CARBOPLATIN; DOCETAXEL; GENOMIC DNA; BRCA1 PROTEIN, HUMAN;

ADULT; AGED; ARTICLE; BASAL LIKE BREAST CANCER; CANCER CHEMOTHERAPY; CANCER PATIENT; CARCINOGENESIS; CONTROLLED STUDY; DEATH; DNA METHYLATION; DRUG EFFICACY; DRUG SAFETY; FEMALE; GENE EXPRESSION; GERMLINE MUTATION; HEADACHE; HOMOLOGOUS RECOMBINATION; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOMAGNESEMIA; MAJOR CLINICAL STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; OVERALL SURVIVAL; PHASE 3 CLINICAL TRIAL; POST TREATMENT SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROMOTER REGION; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TREATMENT RESPONSE; TRIPLE NEGATIVE BREAST CANCER; VOMITING; CLINICAL TRIAL; GENETICS; MUTATION; TREATMENT OUTCOME;

BRCA1 PROTEIN; BRCA2 PROTEIN; CARBOPLATIN; FEMALE; HOMOLOGOUS RECOMBINATION; HUMANS; MUTATION; PROGRESSION-FREE SURVIVAL; TREATMENT OUTCOME; TRIPLE NEGATIVE BREAST NEOPLASMS;

EID: 85046110400     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/s41591-018-0009-7     Document Type: Article

References (50)

1. Kassam, F. et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin. Breast Cancer 9, 29-33 (2009).
2. Sørlie, T. et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. Sci. USA 98, 10869-10874 (2001).
3. Curtis, C. et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346-352 (2012).
4. Lehmann, B. D. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J. Clin. Invest. 121, 2750-2767 (2011).
5. Lehmann, B. D. et al. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PLoS One 11, e0157368 (2016).
6. Burstein, M. D. et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin. Cancer Res. 21, 1688-1698 (2015).
7. Cheang, M. C. et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin. Cancer Res. 14, 1368-1376 (2008).
8. Davies, H. et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat. Med. 23, 517-525 (2017).
9. Catteau, A. & Morris, J. R. BRCA1 methylation: a significant role in tumour development? Semin. Cancer Biol. 12, 359-371 (2002).
10. Xu, Y. et al. Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy. Ann. Oncol. 24, 1498-1505 (2013).
11. Esteller, M. et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J. Natl. Cancer Inst. 92, 564-569 (2000).
12. Baldwin, R. L. et al. BRCA1 promoter region hypermethylation in ovarian carcinoma: a population-based study. Cancer Res. 60, 5329-5333 (2000).
13. Lord, C. J. & Ashworth, A. The DNA damage response and cancer therapy. Nature 481, 287-294 (2012).
14. Levran, O. et al. The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nat. Genet. 37, 931-933 (2005).
15. Taniguchi, T. & D'Andrea, A. D. Molecular pathogenesis of Fanconi anemia: recent progress. Blood 107, 4223-4233 (2006).
16. Venkitaraman, A. R. Tracing the network connecting BRCA and Fanconi anaemia proteins. Nat. Rev. Cancer 4, 266-276 (2004).
17. Tutt, A. N. et al. Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer. Cold Spring Harb. Symp. Quant. Biol. 70, 139-148 (2005).
18. Martín, M. Platinum compounds in the treatment of advanced breast cancer. Clin. Breast Cancer 2, 190-208 (2001).
19. Sledge, G. W. Jr., Loehrer, P. J. Sr., Roth, B. J. & Einhorn, L. H. Cisplatin as first-line therapy for metastatic breast cancer. J. Clin. Oncol. 6, 1811-1814 (1988).
20. Lord, C. J. & Ashworth, A. BRCAness revisited. Nat. Rev. Cancer 16, 110-120 (2016).
21. Turner, N., Tutt, A. & Ashworth, A. Hallmarks of 'BRCAness' in sporadic cancers. Nat. Rev. Cancer 4, 814-819 (2004).
22. Birkbak, N. J. et al. Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents. Cancer Discov. 2, 366-375 (2012).
23. Timms, K. M. et al. Association of BRCA1/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes. Breast Cancer Res. 16, 475 (2014).
24. Popova, T. et al. Ploidy and large-scale genomic instability consistently identify basal-like breast carcinomas with BRCA1/2 inactivation. Cancer Res. 72, 5454-5462 (2012).
25. Watkins, J. et al. Genomic complexity profiling reveals that HORMAD1 overexpression contributes to homologous recombination deficiency in triple-negative breast cancers. Cancer Discov. 5, 488-505 (2015).
26. Telli, M. L. et al. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin. Cancer Res. 22, 3764-3773 (2016).
27. Miles, D. W. et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J. Clin. Oncol. 28, 3239-3247 (2010).
28. Isakoff, S. J. et al. TBCRC009: a multicenter phase II clinical trial of platinum monotherapy with biomarker assessment in metastatic triple-negative breast cancer. J. Clin. Oncol. 33, 1902-1909 (2015).
29. Baselga, J. et al. Randomized phase II study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer. J. Clin. Oncol. 31, 2586-2592 (2013).
30. O'Shaughnessy, J. 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. 32, 3840-3847 (2014).
31. Hu, X. C. et al. Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 16, 436-446 (2015).
32. Turner, N. C. & Reis-Filho, J. S. Basal-like breast cancer and the BRCA1 phenotype. Oncogene 25, 5846-5853 (2006).
33. Han, H. S. et al. Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study. Ann. Oncol. 29, 154-161 (2018).
34. Ter Brugge, P. et al. Mechanisms of therapy resistance in patient-derived xenograft models of BRCA1-deficient breast cancer. J. Natl. Cancer Inst. 108, (2016).
35. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609-615 (2011).
36. Chiang, J. W., Karlan, B. Y., Cass, L. & Baldwin, R. L. BRCA1 promoter methylation predicts adverse ovarian cancer prognosis. Gynecol. Oncol. 101, 403-410 (2006).
37. Swisher, E. M. et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 18, 75-87 (2017).
38. Von Minckwitz, G. et al. Prediction of pathological complete response (pCR) by homologous recombination deficiency (HRD) after carboplatin-containing neoadjuvant chemotherapy in patients with TNBC: results from GeparSixto. J. Clin. Oncol. 33, abstr. 1004 (2015).
39. Mulligan, J. M. et al. Identification and validation of an anthracycline/cyclophosphamide-based chemotherapy response assay in breast cancer. J. Natl. Cancer Inst. 106, djt335 (2014).
40. Wolf, D. et al. Evaluation of an in vitro derived signature of olaparib response (PARPi-7) as a predictive biomarker of response to veliparib/carboplatin plus standard neoadjuvant therapy in high-risk breast cancer: results from the I-SPY 2 TRIAL. Cancer Res. 75, abstr. P3-06-05 (2015).
41. von Minckwitz, G. 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. 15, 747-756 (2014).
42. Sikov, W. M. 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. 33, 13-21 (2015).
43. Geyer, C. E. et al. Phase 3 study evaluating efficacy and safety of veliparib (V) plus carboplatin (Cb) or Cb in combination with standard neoadjuvant chemotherapy (NAC) in patients (pts) with early stage triple-negative breast cancer (TNBC). J. Clin. Oncol. 35, abstr. 520 (2017).
44. Schneeweiss, A. et al. A randomised phase III trial comparing two dose-dense, dose-intensified approaches (EPC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto). J. Clin. Oncol. 35, abstr. 518, poster 118 (2017).
45. Robson, M. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 377, 523-533 (2017).
46. Lord, C. J. & Ashworth, A. PARP inhibitors: synthetic lethality in the clinic. Science 355, 1152-1158 (2017).
47. Huo, D. et al. Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer. J. Clin. Oncol. 27, 4515-4521 (2009).
48. Wallden, B. et al. Development and verification of the PAM50-based Prosigna breast cancer gene signature assay. BMC Med. Genomics 8, 54 (2015).
49. Miller, K. et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Engl. J. Med. 357, 2666-2676 (2007).
50. Royston, P. & Parmar, M. K. Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome. BMC Med. Res. Methodol. 13, 152 (2013).