The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial
Open accessAbstract
Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative ‘BRCAness’ subgroups—tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes—may also be sensitive to platinum. We assessed the efficacy of carboplatin and another mechanistically distinct therapy, docetaxel, in a phase 3 trial in subjects with unselected advanced TNBC. A prespecified protocol enabled biomarker–treatment interaction analyses in gBRCA-BC and BRCAness subgroups. The primary endpoint was objective response rate (ORR). In the unselected population (376 subjects; 188 carboplatin, 188 docetaxel), carboplatin was not more active than docetaxel (ORR, 31.4% versus 34.0%, respectively; P = 0.66). In contrast, in subjects with gBRCA-BC, carboplatin had double the ORR of docetaxel (68% versus 33%, respectively; biomarker, treatment interaction P = 0.01). Such benefit was not observed for subjects with BRCA1 methylation, BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay. Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup. We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations, but not BRCA1 methylation or Myriad HRD analyses, to inform choices on platinum-based chemotherapy. Additionally, gene expression analysis of basal-like cancers may also influence treatment selection. The phase 3 TNT Trial in subjects with triple-negative breast cancer supports the superiority of carboplatin over docetaxel in BRCA1/2-mutated tumors and a greater response to taxanes in the nonbasal subtype.
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Cites
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
METABRIC Group, Curtis, C., Shah, S. P., Chin, S.-F., Turashvili, G., Rueda, O. M., Dunning, M. J., Speed, D., Lynch, A. G., Samarajiwa, S., et al. (2012) · Nature · doi:10.1038/nature10983 · Cited by 6,097
Self-citationPromoter Hypermethylation and BRCA1 Inactivation in Sporadic Breast and Ovarian Tumors
Esteller, M. (2000) · Journal of the National Cancer Institute · doi:10.1093/jnci/92.7.564 · Cited by 1,233
Swisher, E. M., Lin, K. K., Oza, A. M., Scott, C. L., Giordano, H., Sun, J., Konecny, G. E., Coleman, R. L., Tinker, A. V., O'Malley, D. M., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30559-9 · Cited by 1,196
The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia
Levran, O., Attwooll, C., Henry, R. T., Milton, K. L., Neveling, K., Rio, P., Batish, S. D., Kalb, R., Velleuer, E., Barral, S., et al. (2005) · Nature Genetics · doi:10.1038/ng1624 · Cited by 370
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Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation
Litton, J. K., Rugo, H. S., Ettl, J., Hurvitz, S. A., Gonçalves, A., Lee, K.-H., Fehrenbacher, L., Yerushalmi, R., Mina, L. A., Martin, M., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1802905 · Cited by 2,175
Adjuvant Olaparib for Patients with BRCA1 - or BRCA2 -Mutated Breast Cancer
Tutt, A. N. J., Garber, J. E., Kaufman, B., Viale, G., Fumagalli, D., Rastogi, P., Gelber, R. D., de Azambuja, E., Fielding, A., Balmaña, J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105215 · Cited by 1,729
Self-citationGarrido-Castro, A. C., Lin, N. U., & Polyak, K. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1177 · Cited by 1,451
Treatment landscape of triple-negative breast cancer — expanded options, evolving needs
Bianchini, G., De Angelis, C., Licata, L., & Gianni, L. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00565-2 · Cited by 1,382
Schmid, P., Rugo, H. S., Adams, S., Schneeweiss, A., Barrios, C. H., Iwata, H., Diéras, V., Henschel, V., Molinero, L., Chui, S. Y., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30689-8 · Cited by 1,216
Metadata
- Authors
- Tutt, A., Tovey, H., Cheang, M. C. U., Kernaghan, S., Kilburn, L., Gazinska, P., Owen, J., Abraham, J., Barrett, S., Barrett-Lee, P., Brown, R., Chan, S., Dowsett, M., Flanagan, J. M., Fox, L., Grigoriadis, A., Gutin, A., Harper-Wynne, C., Hatton, M. Q., Hoadley, K. A., Parikh, J., Parker, P., Perou, C. M., Roylance, R., Shah, V., Shaw, A., Smith, I. E., Timms, K. M., Wardley, A. M., Wilson, G., Gillett, C., Lanchbury, J. S., Ashworth, A., Rahman, N., Harries, M., Ellis, P., Pinder, S. E., & Bliss, J. M.
- Venue
- Nature Medicine
- Published
- 2018-04-30
- Volume
- 24
- Issue
- 5
- Pages
- 628-637
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2801956643
- Cited by
- 912
- References
- 4
- FWCI
- 59.13
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. https://app.cochat.ai/papers/10.1038/s41591-018-0009-7
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- Tutt, A., Tovey, H., Cheang, M. C. U., Kernaghan, S., Kilburn, L., Gazinska, P., Owen, J., Abraham, J., Barrett, S., Barrett-Lee, P., Brown, R., Chan, S., Dowsett, M., Flanagan, J. M., Fox, L., Grigoriadis, A., Gutin, A., Harper-Wynne, C., Hatton, M. Q., . . . Bliss, J. M. (2018). Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nature Medicine. https://doi.org/10.1038/s41591-018-0009-7
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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