Targeting triple-negative breast cancer: optimizing therapeutic outcomes – UPDATE
Main Article Content
Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous clinical breast cancer subtype that currently lacks approved targeted therapies. Research aimed at understanding the mutational and transcriptional landscape of TNBC is being achieved through gene expression analysis and large-scale genomic projects, resulting in identification of potential drug targets.
Design: A review of PubMed and conference databases was carried out to identify randomized clinical trials in TNBC as well as early phase trials of emerging targeted therapies.
Results and Discussion: The role of platinums and poly(ADP-ribose) polymerase inhibitors continues to be a focus of clinical trials with attention now on developing a predictive biomarker that identifies “BRCA-like” tumours. The previously identified six TNBC subtypes has been revised to four and has provided further insight into the role of the androgen receptor and immune system, both of which are emerging as promising targets in select patients either as monotherapy or in combination with other immune therapies, chemotherapy or targeted therapy. Other novel targets include MET inhibition and signaling pathways such as the MAPK, PI3K and JAK/STAT pathways. Antibody-drug conjugates are also of interest. Targeting the angiogenesis and epidermal growth factor receptor pathways have had limited efficacy in the treatment of TNBC.
Conclusions: As researchers begin to understand the underlying biology of TNBC and identify predictive biomarkers, more select patient populations are being treated with targeted therapies, which is a promising step forward in filling the current void of approved targeted treatment options for patients with TNBC.
Key Words: androgen receptor, breast cancer, breast cancer molecular subtypes, cancer treatment, immune checkpoint blockade, targeted therapy, triple-negative breast cancer.
Article Details
How to Cite
DEN BROK, Wendie D; GELMON, Karen A.
Targeting triple-negative breast cancer: optimizing therapeutic outcomes – UPDATE.
Medical Research Archives, [S.l.], v. 4, n. 6, oct. 2016.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/707>. Date accessed: 24 apr. 2024.
Keywords
androgen receptor, breast cancer, breast cancer molecular subtypes, cancer treatment, immune checkpoint blockade, targeted therapy, triple-negative breast cancer.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Krejci L, Altmannova V, Spirek M, Zhao X. Homologous recombination and its regulation. Nucleic Acids Res. 2012;40(13):5795-5818. doi:10.1093/nar/gks270.
3. Akashi-Tanaka S, Watanabe C, Takamaru T et al. BRCAness predicts resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy. Clin Breast Cancer. 2015;15(1):80-85.
4. Lehmann BDB, Bauer J a J, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750-2767. doi:10.1172/JCI45014DS1.
5. Lehmann BD, Jovanović B, Chen X, et al. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLoS One. 2016;11(6):e0157368. doi:10.1371/journal.pone.0157368.
6. Von Minckwitz G, Schneeweiss A, Loibl S, 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. 2014;15(7):747-756. doi:10.1016/S1470-2045(14)70160-3.
7. Kaklamani VG, Jeruss JS, Hughes E, et al. Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579). Breast Cancer Res Treat. 2015;151(3):629-638. doi:10.1007/s10549-015-3435-y.
8. von Minckwitz G, Oibl S, Schneesweiss A, et al. Early survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S2-04.
9. Sikov WM, Berry DA, Perou CM, 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 (A. J Clin Oncol. 2015;33(1):13-21. doi:10.1200/JCO.2014.57.0572.
10. Telli ML, McMillan A, Ford JM et al. [P3-07-12] Homologous recombination deficiency (HRD) as a predictive biomarker of response to neoadjuvant platinum-based therapy in patients with triple negative breast cancer (TNBC): A pooled analysis. Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-12.
11. Connolly R, Elkin E, Timms K et al. Homologous recombination deficiency (HRD) as a predictive biomarker of response to preoperative systemic therapy (PST) in TBCRC008 comprising a platinum in HER2-negative primary operable breast cancer. Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-13.
12. Tutt A, Ellis P, Kilburn L et al. Abstract S3-01: The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012). Cancer Res. 2015;75:S3-01. doi:10.1158/1538-7445.SABCS14-S3-01.
13. O'Shhaughnessy J, Schwartzberg L, Danso M, 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):3840-3847.
14. Tutt A, Robson M, Garber JE, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376(9737):235-244. doi:10.1016/S0140-6736(10)60892-6.
15. Gelmon K a., Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: A phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011;12(9):852-861. doi:10.1016/S1470-2045(11)70214-5.
16. Robson M, Tutt A, Balmana J et al. OlympiA, Neo-Olympia and OlympiAD: Randomized phase III trials of olaparib in patients (pts) with breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm). Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-1-04.
17. Rugo HS, Olopade OI, DeMichele A, et al. Adaptive Randomization of Veliparib–Carboplatin Treatment in Breast Cancer. N Engl J Med. 2016;375(1):23-34. doi:10.1056/NEJMoa1513749.
18. van t' Veer L, Esserman L, Sanil A, et al. DNA repair deficiency biomarkers identify HR + / HER2- breast cancer patients who may benefit from veliparib / carboplatin : results from the I-SPY 2 TRIAL. J Clin Oncol. 2015;33:(suppl; abstr 521).
19. Miller K, Tong Y, Jones DR et al. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple negative breast cancer: Final efficacy results if Hoosier Oncology Group BRE09-146. J Clin Oncol. 2015;33(suppl; abstr 1082).
20. Rizvi NA, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-128. doi:10.1126/science.aaa1348.
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