Triple‑negative breast cancer therapy: Current and future perspectives (Review)
- Authors:
- Kwang‑Ai Won
- Charles Spruck
-
Affiliations: ConsultantCA, Moraga, CA 94556, USA, Tumor Initiation and Maintenance Program, NCI‑Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA - Published online on: October 16, 2020 https://doi.org/10.3892/ijo.2020.5135
- Pages: 1245-1261
-
Copyright: © Won et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y and Pietenpol JA: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121:2750–2767. 2011.PubMed/NCBI | |
Lehmann BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr Y, Moses HL, Sanders ME and Pietenpol JA: Refinement of triple-negative breast cancer molecular subtypes: Implications for neoadjuvant chemotherapy selection. PLoS One. 11:e01573682016.PubMed/NCBI | |
Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, Weaver DL, Winchester DJ and Hortobagyi GN: Breast cancer-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 67:290–303. 2017.PubMed/NCBI | |
Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, et al: Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American pathologists clinical practice guideline focused update. J Clin Oncol. 36:2105–2122. 2018.PubMed/NCBI | |
Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, et al: Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol. 38:1346–1366. 2020.PubMed/NCBI | |
Yam C, Mani SA and Moulder SL: Targeting the molecular subtypes of triple negative breast cancer: Understanding the diversity to progress the field. Oncologist. 22:1086–1093. 2017.PubMed/NCBI | |
Bonotto M, Gerratana L, Poletto E, Driol P, Giangreco M, Russo S, Minisini AM, Andreetta C, Mansutti M, Pisa FE, et al: Measures of outcome in metastatic breast cancer: Insights from a real-world scenario. Oncologist. 19:608–615. 2014.PubMed/NCBI | |
Kohler BA, Sherman RL, Howlader N, Jemal A, Ryerson AB, Henry KA, Boscoe FP, Cronin KA, Lake A, Noone AM, et al: Annual report to the nation on the status of cancer, 1975-2011 featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst. 107:djv0482015. | |
O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, 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.PubMed/NCBI | |
Caswell-Jin JL, Plevritis SK, Tian L, Cadham CJ, Xu C, Stout NK, Sledge GW, Mandelblatt JS and Kurian AW: Change in survival in metastatic breast cancer with treatment advances: Meta-analysis and systematic review. JNCI Cancer Spectr. 2:pky0622018. | |
Plevritis SK, Munoz D, Kurian AW, Stout NK, Alagoz O, Near AM, Lee SJ, van den Broek JJ, Huang X, Schechter CB, et al: Association of screening and treatment with breast cancer mortality by molecular subtype in US women, 2000-2012. JAMA. 319:154–164. 2018. View Article : Google Scholar : PubMed/NCBI | |
Stanton SE, Adams S and Disis ML: Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: A systematic review. JAMA Oncol. 2:1354–1360. 2016. View Article : Google Scholar : PubMed/NCBI | |
Safonov A, Jiang T, Bianchini G, Győrffy B, Karn T, Hatzis C and Pusztai L: Immune gene expression is associated with genomic aberrations in breast cancer. Cancer Res. 77:3317–3324. 2017. View Article : Google Scholar : PubMed/NCBI | |
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, et al: Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 379:2108–2121. 2018. View Article : Google Scholar : PubMed/NCBI | |
Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Henschel V, Molinero L, Chui SY, et al: Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): Updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 21:44–59. 2020. View Article : Google Scholar | |
Dudley JC, Lin MT, Le DT and Eshleman JR: Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res. 22:813–820. 2016. View Article : Google Scholar : PubMed/NCBI | |
Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen HZ, Reeser JW, Yu L and Roychowdhury S: Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. 2017:PO.17.00073. 2017.PubMed/NCBI | |
Kurata K, Kubo M, Mori H, Kawaji H, Motoyama Y, Kuroki L, Yamada M, Kaneshiro K, Kai M and Nakamura M: Microsatellite instability in triple negative breast cancers. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium. Cancer Res. 79(Suppl 4): Abstract nr P1-06-11. 2019. | |
Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ and Helleday T: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 434:913–917. 2005. View Article : Google Scholar : PubMed/NCBI | |
Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, et al: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 434:917–921. 2005. View Article : Google Scholar : PubMed/NCBI | |
Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, et al: Olaparib for meta-static breast cancer in patients with a germline BRCA mutation. N Engl J Med. 377:523–533. 2017. View Article : Google Scholar : PubMed/NCBI | |
Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, 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. 30:558–566. 2019. View Article : Google Scholar : PubMed/NCBI | |
Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, et al: Talazoparib in patients with advanced breast cancer and a germ-line BRCA mutation. N Engl J Med. 379:753–763. 2018. View Article : Google Scholar : PubMed/NCBI | |
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, Budczies J, Huober J, Klauschen F, Furlanetto J, et al: Tumour-infiltrating lymphocytes and prog-nosis in different subtypes of breast cancer: A pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 19:40–50. 2018. View Article : Google Scholar | |
Hida AI, Watanabe T, Sagara Y, Kashiwaba M, Sagara Y, Aogi K, Ohi Y and Tanimoto A: Diffuse distribution of tumor-infiltrating lymphocytes is a marker for better prognosis and chemo-therapeutic effect in triple-negative breast cancer. Breast Cancer Res Treat. 178:283–294. 2019. View Article : Google Scholar : PubMed/NCBI | |
Loi S, Drubay D, Adams S, Pruneri G, Francis PA, Lacroix-Triki M, Joensuu H, Dieci MV, Badve S, Demaria S, et al: Tumor-infiltrating lymphocytes and prognosis: A pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol. 37:559–569. 2019. View Article : Google Scholar : PubMed/NCBI | |
Galon J and Bruni D: Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 18:197–218. 2019. View Article : Google Scholar : PubMed/NCBI | |
Adams S, Gatti-Mays ME, Kalinsky K, Korde LA, Sharon E, Amiri-Kordestani L, Bear H, McArthur HL, Frank E, Perlmutter J, et al: Current landscape of immunotherapy in breast cancer: A review. JAMA Oncol. Apr 11–2019.Epub ahead of print. View Article : Google Scholar | |
Schmid P, Salgado R, Park YH, Muñoz-Couselo E, Kim SB, Sohn J, Im S-A, Foukakis T, Kuemmel S, Dent R, et al: Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: Results from the phase 1b open-label, multicohort KEYNOTE-173 study. Ann Oncol. 31:569–581. 2020. View Article : Google Scholar : PubMed/NCBI | |
Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, et al: Effect of pembrolizumab plus neoadjuvant chemotherapy on Pathologic complete response in women with early-stage breast cancer: An analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 6:1–9. 2020. View Article : Google Scholar | |
Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, et al: Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 382:810–821. 2020. View Article : Google Scholar : PubMed/NCBI | |
Gianni L, Huang CS, Egle D, Bermejo B, Zamagni C, Thill M, Anton A, Zambelli S, Bianchini G, Russo S and Ciruelos E: Pathologic complete response (pCR) to neoadjvaunt treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium. Cancer Res. 80(Suppl 4): Abstract nr GS3-04. 2020. | |
Mittendorf E, Barrios CH, Harbeck N, Miles D, Saji S, Zhang H, Duc AN, Rafii S and Lai C: IMpassion031: A phase III study comparing neoadjuvant atezolizumab vs placebo in combination with nab-paclitaxel-based chemotherapy in early triple-negative breast cancer (TNBC). In: Proceedings of the 2017 San Antonio Breast Cancer Symposium. Cancer Res. 78(Suppl 4): Abstract nr OT2-07-03. 2018. | |
Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, et al: KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or meta-static triple-negative breast cancer. J Clin Oncol. 38(Suppl 15): S1000. 2020. View Article : Google Scholar | |
Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, Nederlof I, Kluin RJC, Warren S, Ong S, et al: Immune induction strategies in meta-static triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: The TONIC trial. Nat Med. 25:920–928. 2019. View Article : Google Scholar : PubMed/NCBI | |
Allard B, Longhi MS, Robson SC and Stagg J: The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets. Immunol Rev. 276:121–144. 2017. View Article : Google Scholar : PubMed/NCBI | |
Ghalamfarsa G, Kazemi MH, Raoofi Mohseni S, Masjedi A, Hojjat-Farsangi M, Azizi G, Yousefi M and Jadidi-Niaragh F: CD73 as a potential opportunity for cancer immunotherapy. Expert Opin Ther Targets. 23:127–142. 2019. View Article : Google Scholar | |
Duhant X, Schandené L, Bruyns C, Gonzalez NS, Goldman M, Boeynaems JM and Communi D: Extracellular adenine nucleotides inhibit the activation of human CD4+ T lymphocytes. J Immunol. 169:15–21. 2002. View Article : Google Scholar : PubMed/NCBI | |
Allard B, Beavis PA, Darcy PK and Stagg J: Immunosuppressive activities of adenosine in cancer. Curr Opin Pharmacol. 29:7–16. 2016. View Article : Google Scholar : PubMed/NCBI | |
Ohta A: A metabolic immune checkpoint: Adenosine in tumor microenvironment. Front Immunol. 7:1092016. View Article : Google Scholar : PubMed/NCBI | |
Buisseret L, Pommey S, Allard B, Garaud S, Bergeron M, Cousineau I, Ameye L, Bareche Y, Paesmans M, Crown JPA, et al: Clinical significance of CD73 in triple-negative breast cancer: Multiplex analysis of a phase III clinical trial. Ann Oncol. 29:1056–1062. 2018. | |
Powderly J, Spira A, Gutierrez R, DiRenzo D, Udyavar A, Karakunnel JJ, Rieger A, Colabella J, Lai DW and de Souza P: Phase 1 evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients with advanced malignancies. Ann Oncol. 30(Suppl 5): v475–v532. 2019. | |
Hartman AR, Kaldate RR, Sailer LM, Painter L, Grier CE, Endsley RR, Griffin M, Hamilton SA, Frye CA, Silberman MA, et al: Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer. Cancer. 118:2787–2795. 2012.PubMed/NCBI | |
Okuma HS and Yonemori K: BRCA gene mutations and poly(ADP-Ribose) polymerase inhibitors in triple-negative breast cancer. Adv Exp Med Biol. 1026:271–286. 2017.PubMed/NCBI | |
Lord CJ and Ashworth A: BRCAness revisited. Nat Rev Cancer. 16:110–120. 2016.PubMed/NCBI | |
Litton JK, Scoggins ME, Hess KR, Adrada BE, Murthy RK, Damodaran S, DeSnyder SM, Brewster AM, Barcenas CH, Valero V, et al: Neoadjuvant talazoparib for patients with operable breast cancer with a germline BRCA pathogenic variant. J Clin Oncol. 38:388–394. 2020. | |
Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, et al: Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): A randomised, phase 3 trial. Lancet Oncol. 19:497–509. 2018.PubMed/NCBI | |
Jiao S, Xia W, Yamaguchi H, Wei Y, Chen MK, Hsu JM, Hsu JL, Yu WH, Du Y, Lee HH, et al: PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res. 23:3711–3720. 2017.PubMed/NCBI | |
Vinayak S, Tolaney SM, Schwartzberg L, Mita M, McCann G, Tan AR, Wahner-Hendrickson AE, Forero A, Anders C, Wulf GM, et al: Open-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer. JAMA Oncol. 5:1132–1140. 2019. | |
Domchek S, Postel-Vinay S, Im S, Park YH, Delord J, Italiano A, Alexandre J, You B, Bastian S, Krebs MG, et al: Phase II study of olaparib (o) and durvalumab (d) (MEDIOLA): Updated results in patients (pts) with germline BRCA-mutated (gBRCAm) meta-static breast cancer (mbc). Ann Oncol. 30(Suppl 5): v475–v532. 2019. | |
Pusztai L, Han HS, Yau C, Wolf D, Wallace AM, Shatsky R, Helsten T, Boughey JC, Haddad T, Stringer-Reasor E, et al: Durvalumab in combination with olaparib and paclitaxel in high-risk HER2 negative stage II/III breast cancer: Results from the I-SPY 2 trial. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020. Cancer Res. 80(Suppl 16): Abstract nr CT011. 2020. | |
Mitri ZI, Vuky J, Kemmer KA, Savin MA, Parmar S, Kolodzie AK, Johnson B, Williams-Belizaire R, Gray JW and Mills GB: A phase II trial of olaparib and durvalumab in metastatic BRCA wild type triple-negative breast cancer. J Clin Oncol. 37:TPS11112019. | |
Rugo HS, Llombart-Cussac A, Andre F, Robson ME, Saji S, Harbeck N, Schmid P, Cescon DW, Ahn JS, Nanda R, et al: KEYLYNK-009: A phase II/III, open-label, randomized study of pembrolizumab (pembro) plus olaparib vs pembro plus chemotherapy after induction with first-line pembro plus chemo-therapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC). J Clin Oncol. 38:TPS5962020. | |
Maacke H, Opitz S, Jost K, Hamdorf W, Henning W, Krüger S, Feller AC, Lopens A, Diedrich K, Schwinger E and Stürzbecher HW: Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer. Int J Cancer. 88:907–913. 2000.PubMed/NCBI | |
Martin RW, Orelli BJ, Yamazoe M, Minn AJ, Takeda S and Bishop DK: RAD51 up-regulation bypasses BRCA1 function and is a common feature of BRCA1-deficient breast tumors. Cancer Res. 67:9658–9665. 2007.PubMed/NCBI | |
Wiegmans AP, Yap PY, Ward A, Lim YC and Khanna KK: Differences in expression of key DNA damage repair genes after epigenetic-induced BRCAness dictate synthetic lethality with PARP1 inhibition. Mol Cancer Ther. 14:2321–2331. 2015.PubMed/NCBI | |
Liu Y, Burness ML, Martin-Trevino R, Guy J, Bai S, Harouaka R, Brooks MD, Shang L, Fox A, Luther TK, et al: RAD51 mediates resistance of cancer stem cells to PARP inhibition in triple-negative breast cancer. Clin Cancer Res. 23:514–522. 2017. | |
Marzio A, Puccini J, Kwon Y, Maverakis NK, Arbini A, Sung P, Bar-Sagi D and Pagano M: The F-Box domain-dependent activity of EMI1 regulates PARPi sensitivity in triple-negative breast cancers. Mol Cell. 73:224–237.e6. 2019. | |
Tutt A, Stephens C, Frewer P, Pierce A, Rhee J, So K, Ottesen L, Dean E and Hollingsworth SJ: VIOLETTE: A randomized phase II study to assess DNA damage response inhibitors in combination with olaparib (Ola) vs. Ola monotherapy in patients (pts) with metastatic, triple-negative breast cancer (TNBC) stratified by alterations in homologous recombination repair (HRR)-related genes. J Clin Oncol. 36(Suppl 15): TPS11122018. | |
Hirai H, Arai T, Okada M, Nishibata T, Kobayashi M, Sakai N, Imagaki K, Ohtani J, Sakai T, Yoshizumi T, et al: MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biol Ther. 9:514–522. 2010.PubMed/NCBI | |
Pitts TM, Simmons DM, Bagby SM, Hartman SJ, Yacob BW, Gittleman B, Tentler JJ, Cittelly D, Ormond DR, Messersmith WA, et al: Wee1 inhibition enhances the anti-tumor effects of capecitabine in preclinical models of triple-negative breast cancer. Cancers (Basel). 12:7192020. View Article : Google Scholar | |
Do K, Wilsker D, Ji J, Zlott J, Freshwater T, Kinders RJ, Collins J, Chen AP, Doroshow JH and Kummar S: Phase I study of single-agent AZD1775 (MK-1775), a Wee1 kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol. 33:3409–3415. 2015. View Article : Google Scholar : PubMed/NCBI | |
Do KT, Hill SJ, Kochupurakkal B, Supko JG, Gannon C, Anderson A, Muzikansky A, Wolanski A, Hedglin J, Parmar K, et al: Abstract CT232: Phase I combination study of the CHK1 inhibitor prexasertib (LY2606368) and olaparib in patients with high-grade serous ovarian cancer and other advanced solid tumors. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019. Cancer Res. 79(Suppl 13): Abstract nr CT232. 2019. | |
Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, Xu C, McKenzie JA, Zhang C, Liang X, et al: Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 6:202–216. 2016. View Article : Google Scholar : | |
André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, et al: Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 380:1929–1940. 2019. View Article : Google Scholar | |
Kim SB, Dent R, Im SA, Espié M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, et al: Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): A multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 18:1360–1372. 2017. View Article : Google Scholar : PubMed/NCBI | |
Dent R, Im SA, Espie M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko M, Kapp AV, et al: Overall survival (OS) update of the double-blind placebo (PBO)-controlled random-ized phase 2 LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for locally advanced/metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 36:10082018. View Article : Google Scholar | |
Dent R, Kim SB, Oliveira M, Isakoff SJ, Barrios CH, O'Shaughnessy J, Lu X, Wongchenko M, Bradley D, Mani A, et al: IPATunity130: A pivotal randomized phase III trial evaluating ipatasertib (IPAT) + paclitaxel (PAC) for PIK3CA/AKT1/PTEN-altered advanced triple-negative (TN) or hormone receptor-positive HER2-negative (HR+/HER2-) breast cancer (BC). J Clin Oncol. 36(Suppl 15): TPS11172018. View Article : Google Scholar | |
Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, et al: Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: The PAKT trial. J Clin Oncol. 38:423–433. 2020. View Article : Google Scholar | |
Schmid P, Cortes J, Robson M, Iwata H, Hegg R, Verma S, Nechaeva M, Xu B, Haddad V, Imedio RE, et al: Abstract OT2-08-02: Capivasertib and paclitaxel in first-line treatment of patients with metastatic triple-negative breast cancer: A phase III trial (CAPItello-290). In: Proceedings of the 2019 San Antonio Breast Cancer Symposium. Cancer Res. 80(Suppl 4): Abstract nr OT2-08-02. 2020. | |
Schmid P, Loirat D, Savas P, Espinosa E, Boni V, Italiano A, White S, Singel MS, Withana N, Mani A, et al: Phase Ib study evaluating a triplet combination of ipatasertib (IPAT), atezoli-zumab (atezo), and paclitaxel (PAC) or nab-PAC as first-line (1L) therapy for locally advanced/metastatic triple-negative breast cancer (TNBC). In: Proceedings of the American Association for Cancer Research Annual Meeting 2019. Cancer Res. 79(Suppl 13): Abstract nr CT049. 2019. | |
Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI | |
Dean JL, McClendon AK and Knudsen ES: Modification of the DNA damage response by therapeutic CDK4/6 inhibition. J Biol Chem. 287:29075–29087. 2012. View Article : Google Scholar : PubMed/NCBI | |
Cretella D, Fumarola C, Bonelli M, Alfieri R, La Monica S, Digiacomo G, Cavazzoni A, Galetti M, Generali D and Petronini PG: Pre-treatment with the CDK4/6 inhibitor palbociclib improves the efficacy of paclitaxel in TNBC cells. Sci Rep. 9:130142019. View Article : Google Scholar : PubMed/NCBI | |
Clark AS, McAndrew NP, Troxel A, Feldman M, Lal P, Rosen M, Burrell J, Redlinger C, Gallagher M, Bradbury AR, et al: Combination paclitaxel and palbociclib: Results of a phase I trial in advanced breast cancer. Clin Cancer Res. 25:2072–2079. 2019. View Article : Google Scholar : PubMed/NCBI | |
Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnović Ž, Vasev N, Ma L, et al: Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: A multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 20:1587–1601. 2019. View Article : Google Scholar : PubMed/NCBI | |
Stine ZE, Walton ZE, Altman BJ, Hsieh AL and Dang CV: MYC, metabolism, and cancer. Cancer Discov. 5:1024–1039. 2015. View Article : Google Scholar : PubMed/NCBI | |
Ambrosio S, Amente S, Napolitano G, Di Palo G, Lania L and Majello B: MYC impairs resolution of site-specific DNA double-strand breaks repair. Mutat Res. 774:6–13. 2015. View Article : Google Scholar : PubMed/NCBI | |
Wiegmans AP, Al-Ejeh F, Chee N, Yap PY, Gorski JJ, Da Silva L, Bolderson E, Chenevix-Trench G, Anderson R, Simpson PT, et al: Rad51 supports triple negative breast cancer metastasis. Oncotarget. 5:3261–3272. 2014. View Article : Google Scholar : PubMed/NCBI | |
Carey JPW, Karakas C, Bui T, Chen X, Vijayaraghavan S, Zhao Y, Wang J, Mikule K, Litton JK, Hunt KK and Keyomarsi K: Synthetic lethality of PARP inhibitors in combination with MYC blockade is independent of BRCA status in triple negative breast cancer. Cancer Res. 78:742–757. 2018. View Article : Google Scholar : | |
Horiuchi D, Kusdra L, Huskey NE, Chandriani S, Lenburg ME, Gonzalez-Angulo AM, Creasman KJ, Bazarov AV, Smyth JW, Davis SE, et al: MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition. J Exp Med. 209:679–696. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hossain DMS, Javaid S, Cai M, Zhang C, Sawant A, Hinton M, Sathe M, Grein J, Blumenschein W, Pinheiro EM and Chackerian A: Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor suppression. J Clin Invest. 128:644–654. 2018. View Article : Google Scholar : PubMed/NCBI | |
Chien AJ, Gliwa AS, Rahmaputri S, Dittrich HF, Majure MC, Rugo HS, Melisko ME, Munster PN, Park JW, Moasser MM, et al: A phase Ib trial of the cyclin-dependent kinase inhibitor dinaci-clib (dina) in combination with pembrolizumab (P) in patients with advanced triple-negative breast cancer (TNBC) and response correlation with MYC-overexpression. J Clin Oncol. 38(1076)2020. View Article : Google Scholar | |
Kono M, Fujii T, Lim B, Karuturi MS, Tripathy D and Ueno NT: Androgen receptor function and androgen receptor-targeted therapies in breast cancer: A Review. JAMA Oncol. 3:1266–1273. 2017. View Article : Google Scholar : PubMed/NCBI | |
Gerratana L, Basile D, Buono G, De Placido S, Giuliano M, Minichillo S, Coinu A, Martorana F, De Santo I, Del Mastro L, et al: Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype. Cancer Treat Rev. 68:102–110. 2018. View Article : Google Scholar : PubMed/NCBI | |
Anestis A, Zoi I, Papavassiliou AG and Karamouzis MV: Androgen receptor in breast cancer-clinical and preclinical research insights. Molecules. 25(358)2020. View Article : Google Scholar : PubMed/NCBI | |
Masuda H, Baggerly KA, Wang Y, Zhang Y, Gonzalez-Angulo AM, Meric-Bernstam F, Valero V, Lehmann BD, Pietenpol JA, Hortobagyi GN, et al: Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res. 19:5533–5540. 2013. View Article : Google Scholar : PubMed/NCBI | |
Thike AA, Yong-Zheng Chong L, Cheok PY, Li HH, Wai-Cheong Yip G, Huat Bay B, Tse GM, Iqbal J and Tan PH: Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer. Mod Pathol. 27:352–360. 2014. View Article : Google Scholar | |
Echavarria I, Lopez-Tarruella S, Picornell A, García-Saenz JA, Jerez Y, Hoadley K, Gómez HL, Moreno F, Monte-Millan MD, Márquez-Rodas I, et al: Pathological response in a triple-negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification. Clin Cancer Res. 24:1845–1852. 2018. View Article : Google Scholar : PubMed/NCBI | |
Santonja A, Sánchez-Muñoz A, Lluch A, Chica-Parrado MR, Albanell J, Chacón JI, Antolín S, Jerez JM, de la Haba J, de Luque V, et al: Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy. Oncotarget. 9:26406–26416. 2018. View Article : Google Scholar : PubMed/NCBI | |
Venema CM, Bense RD, Steenbruggen TG, Nienhuis HH, Qiu SQ, van Kruchten M, Brown M, Tamimi RM, Hospers GAP, Schröder CP, et al: Consideration of breast cancer subtype in targeting the androgen receptor. Pharmacol Ther. 200:135–147. 2019. View Article : Google Scholar : PubMed/NCBI | |
Rice MA, Malhotra SV and Stoyanova T: Second-generation antiandrogens: From discovery to standard of care in castration resistant prostate cancer. Front Oncol. 9:8012019. View Article : Google Scholar : PubMed/NCBI | |
Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, et al: Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res. 19:5505–5512. 2013. View Article : Google Scholar : PubMed/NCBI | |
Gucalp A, Edelweiss M, Patil S, Gounder MM, Feigin KN, Corben A, Arumov A and Traina TA: Abstract P3-11-04: Phase I/II trial of palbociclib in combination with bicalutamide for the treatment of androgen receptor (AR)+ metastatic breast cancer (MBC). In: Proceedings of the 2017 San Antonio Breast Cancer Symposium. Cancer Res 2018. 78(Suppl 4): Abstract nr P3-11-04. 2018. | |
Gucalp A, Boyle LA, Alano T, Arumov A, Gounder MM, Patil S, Feigin K, Edelweiss M, D'Andrea G, Bromberg J, et al: Phase II trial of bicalutamide in combination with palbociclib for the treatment of androgen receptor (+) metastatic breast cancer. J Clin Oncol. 38:2020. View Article : Google Scholar | |
Bonnefoi H, Grellety T, Tredan O, Saghatchian M, Dalenc F, Mailliez A, L'Haridon T, Cottu P, Abadie-Lacourtoisie S, You B, et al: A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 27:812–818. 2016. View Article : Google Scholar : PubMed/NCBI | |
Gucalp A, Danso MA, Elias AD, Bardia A, Ali HY, Potter D, Gabrail NY, Haley BB, Khong HT, Riley EC, et al: Phase (Ph) 2 stage 1 clinical activity of seviteronel, a selective CYP17-lyase and androgen receptor (AR) inhibitor, in women with advanced AR+ triple-negative breast cancer (TNBC) or estrogen receptor (ER)+ BC: CLARITY-01. J Clin Oncol. 35:11022017. View Article : Google Scholar | |
Bardia A, Gucalp A, DaCosta N, Gabrail N, Danso M, Ali H, Blackwell KL, Carey LA, Eisner JR, Baskin-Bey ES and Traina TA: Phase 1 study of seviteronel, a selective CYP17 lyase and androgen receptor inhibitor, in women with estrogen receptor-positive or triple-negative breast cancer. Breast Cancer Res Treat. 171:111–120. 2018. View Article : Google Scholar : PubMed/NCBI | |
Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, et al: Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol. 36:884–890. 2018. View Article : Google Scholar : PubMed/NCBI | |
Dent R, Schmid P, Cortes J, Kim SB, Andre F, Abramson V, Cardoso F, Colleoni M, Morris P, Steinberg J, et al: Abstract OT3-02-02: ENDEAR: A randomized international phase 3 study comparing the efficacy and safety of enzalutamide in combination with paclitaxel chemotherapy or as mono-therapy vs placebo with paclitaxel in patients with advanced diagnostic-positive triple-negative breast cancer. Cancer Res. 77:Abstract OT3-02-02. 2017. | |
Lehmann BD, Abramson VG, Sanders ME, Mayer EL, Haddad TC, Nanda R, Van Poznak C, Storniolo AM, Nangia JR, Gonzalez-Ericsson PI, et al: TBCRC 032 IB/II multicenter study: Molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR+ metastatic triple-negative breast cancer. Clin Cancer Res. 26:2111–2123. 2020. View Article : Google Scholar | |
Gilewski T, Ragupathi G, Bhuta S, Williams LJ, Musselli C, Zhang XF, Bornmann WG, Spassova M, Bencsath KP, Panageas KS, et al: Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial. Proc Natl Acad Sci USA. 98:3270–3275. 2001. View Article : Google Scholar : PubMed/NCBI | |
Huang CS, Yu AL, Tseng LM, Chow LWC, Hou MF, Hurvitz SA, Schwab RB, Wong CH, Murray JL, Chang SC, et al: Randomized phase II/III trial of active immunotherapy with OPT-822/OPT-821 in patients with metastatic breast cancer. J Clin Oncol. 34(Suppl 15): S10032016. View Article : Google Scholar | |
Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Abramson VG, et al: Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Eng J Med. 380:741–751. 2019. View Article : Google Scholar | |
Modi S, Pusztai L, Forero A, Mita M, Miller KD, Weise A, Burris H III, Kalinsky K, Tsai M, Liu MC, et al: Abstract PD3-14: Phase 1 study of the antibody-drug conjugate SGN-LIV1A in patients with heavily pretreated triple-negative metastatic breast cancer. Cancer Res. 78:2018. | |
Han HS, Alemany CA, Brown-Glaberman UA, Pluard TJ, Sinha R, Sterrenberg D, Albain KS, Basho RK, Biggs D, Boni V, et al: SGNLVA-002: Single-arm, open label phase Ib/II study of ladiratuzumab vedotin (LV) in combination with pembrolizumab for first-line treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer. J Clin Oncol. 37(Suppl 15): TPS11102019. View Article : Google Scholar | |
Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, et al: Antitumor activity and safety of trastuzumab Deruxtecan in patients with HER2-low-expressing advanced breast cancer: Results from a phase Ib study. J Clin Oncol. 38:1887–1896. 2020. View Article : Google Scholar : PubMed/NCBI | |
Modi S, Ohtani S, Lee CC, Wang K, Saxena K and Cameron DA: A phase III, multicenter, randomized, open label trial of [fam-] trastuzumab deruxtecan (DS-8201a) versus investigator's choice in HER2-low breast cancer. J Clin Oncol. 37(Suppl 15): TPS11022019. View Article : Google Scholar | |
Molyneux G, Geyer FC, Magnay FA, McCarthy A, Kendrick H, Natrajan R, Mackay A, Grigoriadis A, Tutt A, Ashworth A, et al: BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell. 7:403–417. 2010. View Article : Google Scholar : PubMed/NCBI | |
Bernardo GM, Bebek G, Ginther CL, Sizemore ST, Lozada KL, Miedler JD, Anderson LA, Godwin AK, Abdul-Karim FW, Slamon DJ and Keri RA: FOXA1 represses the molecular pheno-type of basal breast cancer cells. Oncogene. 32:554–563. 2013. View Article : Google Scholar | |
Su Y, Subedee A, Bloushtain-Qimron N, Savova V, Krzystanek M, Li L, Marusyk A, Tabassum DP, Zak A, Flacker MJ, et al: Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer. Cell Rep. 11:1549–1563. 2015. View Article : Google Scholar : PubMed/NCBI | |
Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS and Zhang Y: Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. 298:1039–1043. 2002. View Article : Google Scholar : PubMed/NCBI | |
Yamagishi M and Uchimaru K: Targeting EZH2 in Cancer Therapy. Curr Opin Oncol. 29:375–381. 2017. View Article : Google Scholar : PubMed/NCBI | |
Yang CC, LaBaff A, Wei Y, Nie L, Xia W, Huo L, Yamaguchi H, Hsu YH, Hsu JL, Liu D, et al: Phosphorylation of EZH2 at T416 by CDK2 contributes to the malignancy of triple negative breast cancers. Am J Transl Res. 7:1009–1020. 2015.PubMed/NCBI | |
Nie L, Wei Y, Zhang F, Hsu YH, Chan LC, Xia W, Ke B, Zhu C, Deng R, Tang J, et al: CDK2-mediated site-specific phosphorylation of EZH2 drives and maintains triple-negative breast cancer. Nat Commun. 10:51142019. View Article : Google Scholar : PubMed/NCBI | |
Yang X, Phillips DL, Ferguson AT, Nelson WG, Herman JG and Davidson NE: Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells. Cancer Res. 61:7025–7029. 2001.PubMed/NCBI | |
Sharma D, Saxena NK, Davidson NE and Vertino PM: Restoration of tamoxifen sensitivity in estrogen receptor-negative breast cancer cells: Tamoxifen-bound reactivated ER recruits distinctive corepressor complexes. Cancer Res. 66:6370–6378. 2006. View Article : Google Scholar : PubMed/NCBI | |
Connolly RM, Li H, Jankowitz RC, Zhang Z, Rudek MA, Jeter SC, Slater SA, Powers P, Wolff AC, Fetting JH, et al: Combination epigenetic therapy in advanced breast cancer with 5-azacitidine and entinostat: A phase II National Cancer Institute/Stand up to cancer study. Clin Cancer Res. 23:2691–2701. 2017. View Article : Google Scholar : | |
Anderberg C, Li H, Fredriksson L, Andrae J, Betsholtz C, Li X, Eriksson U and Pietras K: Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by recruitment of cancer-associated fibroblasts. Cancer Res. 69:369–378. 2009. View Article : Google Scholar : PubMed/NCBI | |
Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S, Lehn S, Sjölund J, Reid S, Larsson C, et al: Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. Nat Med. 24:463–473. 2018. View Article : Google Scholar : PubMed/NCBI | |
Park JJH, Hsu G, Siden EG, Thorlund K and Mills EJ: An overview of precision oncology basket and umbrella trials for clinicians. CA Cancer J Clin. 70:125–137. 2020. View Article : Google Scholar : PubMed/NCBI |