Emerging drugs for the treatment of triple-negative breast cancer: a focus on phase II immunotherapy trials

References

• Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394–424. PubMed PMID: 30207593; eng.
   PubMed Web of Science ®Google Scholar
• Global Caner Observatory. Cancer tomorrow. [cited 2020 Sep 20]. Available from: https://gco.iarc.fr/tomorrow/home.
   Google Scholar
• Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019 Aug 1;30(8):1194–1220. PubMed PMID: 31161190; eng.
   PubMed Web of Science ®Google Scholar
• Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 4)†. Ann Oncol. 2018 Aug 1;29(8):1634–1657. PubMed PMID: 30032243; PubMed Central PMCID: PMCPMC7360146. eng.
   PubMed Web of Science ®Google Scholar
• Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol. 2012 Aug;23(Suppl 6):vi7–12. PubMed PMID: 23012306; eng.
   PubMed Web of Science ®Google Scholar
• Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010 Jul 10;28(20):3271–3277. PubMed PMID: 20498394; eng.
   PubMed Web of Science ®Google Scholar
• Metzger-Filho O, Sun Z, Viale G, et al. Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. J Clin Oncol. 2013 Sep 1;31(25):3083–3090. PubMed PMID: 23897954; PubMed Central PMCID: PMCPMC3753700 found at the end of this article. eng.
   PubMed Web of Science ®Google Scholar
• Li X, Yang J, Peng L, et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. 2017 Jan;161(2):279–287. PubMed PMID: 27888421; eng.
   PubMed Web of Science ®Google Scholar
• Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018 Nov 29;379(22):2108–2121. PubMed PMID: 30345906; eng.
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network (NCCN). NCCN guidelines breast cancer. 2020. [cited 2020 Sep 20]. Available from: https://www.nccn.org/professionals/physician_gls/default.aspx#breast.
   Google Scholar
• Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164–172. PubMed PMID: 24529560; eng.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). Clinical trial endpoints for the approval of cancer drugs and biologics guidance for industry. 2018. [cited 2020 Sep 20]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-trial-endpoints-approval-cancer-drugs-and-biologics.
   Google Scholar
• Lm S, Fell G, Arfe A, et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res. 2020 Jun 15;26(12):2838–2848. PubMed PMID: 32046998; PubMed Central PMCID: PMCPMC7299787. eng.
   PubMed Web of Science ®Google Scholar
• Huang M, O’Shaughnessy J, Zhao J, et al. Association of pathologic complete response with long-term survival outcomes in triple-negative breast cancer: a meta-analysis. Cancer Res. 2020 Dec 15;80(24):5427–5434. PubMed PMID: 32928917; eng.
   PubMed Web of Science ®Google Scholar
• Loibl S, O’Shaughnessy J, Untch M, 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. 2018 Apr;19(4):497–509. PubMed PMID: 29501363; eng.
   PubMed Web of Science ®Google Scholar
• 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 Jun;15(7):747–756. PubMed PMID: 24794243; eng.
   PubMed Web of Science ®Google Scholar
• Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020 Feb 27;382(9):810–821. PubMed PMID: 32101663; eng.
   PubMed Web of Science ®Google Scholar
• Mittendorf EA, Zhang H, Barrios CH, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Oct 10;396(10257):1090–1100. PubMed PMID: 32966830; eng.
   PubMed Web of Science ®Google Scholar
• Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017 Jun 1;376(22):2147–2159. PubMed PMID: 28564564; eng.
   PubMed Web of Science ®Google Scholar
• Dear RF, McGeechan K, Jenkins MC, et al. Combination versus sequential single agent chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev. 2013 Dec;18(12):Cd008792. PubMed PMID: 24347031; eng.
   Google Scholar
• Katsumata N, Watanabe T, Minami H, et al. Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan clinical oncology group trial (JCOG9802). Ann Oncol. 2009 Jul;20(7):1210–1215. PubMed PMID: 19254942; eng.
   PubMed Web of Science ®Google Scholar
• Tutt A, Tovey H, Cheang MCU, et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628–637. PubMed PMID: 29713086; PubMed Central PMCID: PMCPMC6372067. eng.
   PubMed Web of Science ®Google Scholar
• Sparano JA, Vrdoljak E, Rixe O, et al. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256–3263. PubMed PMID: 20530276; PubMed Central PMCID: PMCPMC2903325 found at the end of this article. eng.
   PubMed Web of Science ®Google Scholar
• Thomas ES, Gomez HL, Li RK, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210–5217. PubMed PMID: 17968020; eng.
   PubMed Web of Science ®Google Scholar
• Pallis AG, Boukovinas I, Ardavanis A, et al. A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer. Ann Oncol. 2012 May;23(5):1164–1169. PubMed PMID: 21937705; eng.
   PubMed Web of Science ®Google Scholar
• Martín M, Ruiz A, Muñoz M, et al. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish breast cancer research group (GEICAM) trial. Lancet Oncol. 2007 Mar 8;8(3):219–225. PubMed PMID: 17329192; eng.
   PubMed Web of Science ®Google Scholar
• Pivot X, Marmé F, Koenigsberg R, et al. Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy. Ann Oncol. 2016 Aug;27(8):1525–1531. PubMed PMID: 27177860; PubMed Central PMCID: PMCPMC4959925. eng.
   PubMed Web of Science ®Google Scholar
• Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial offirst-line paclitaxel (PAC) ±atezolizumab (atezo) for unresectable locally advanced/metastatictriple-negative breast cancer (mTNBC). Ann Oncol. 2020;20(Suppl 4):S1142.
   Google Scholar
• Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817–1828. PubMed PMID: 33278935; eng.
   PubMed Web of Science ®Google Scholar
• Engel C, Rhiem K, Hahnen E, et al. Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history. BMC Cancer. 2018 Mar 7;18(1):265. PubMed PMID: 29514593; PubMed Central PMCID: PMCPMC5842578. eng.
   PubMedGoogle Scholar
• Sharma P, Klemp JR, Kimler BF, et al. Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing. Breast Cancer Res Treat. 2014 Jun;145(3):707–714. PubMed PMID: 24807107; PubMed Central PMCID: PMCPMC4171847. eng.
   PubMed Web of Science ®Google Scholar
• Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523–533. PubMed PMID: 28578601; eng.
   PubMed Web of Science ®Google Scholar
• Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753–763. PubMed PMID: 30110579; eng.
   PubMed Web of Science ®Google Scholar
• Robson ME, Tung N, Conte P, 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 Apr 1;30(4):558–566. PubMed PMID: 30689707; PubMed Central PMCID: PMCPMC6503629. eng.
   PubMed Web of Science ®Google Scholar
• Litton JK, Hurvitz SA, Mina LA, et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Aug 20;31(11):1526–1535. PubMed PMID: 32828825; eng.
   PubMed Web of Science ®Google Scholar
• Tung NM, Robson ME, Ventz S, et al. TBCRC 048: phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes. J Clin Oncol. 2020 Oct 29:Jco2002151. PubMed PMID: 33119476; eng. 10.1200/jco.20.02151
   Google Scholar
• Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004 May 3;3(5):391–400. PubMed PMID: 15136787; eng.
   PubMed Web of Science ®Google Scholar
• Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666–2676. PubMed PMID: 18160686; eng.
   PubMed Web of Science ®Google Scholar
• Miles DW, Chan A, Dirix LY, 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. 2010 Jul 10;28(20):3239–3247. PubMed PMID: 20498403; eng.
   PubMed Web of Science ®Google Scholar
• Nj R, Diéras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252–1260. PubMed PMID: 21383283; eng.
   PubMed Web of Science ®Google Scholar
• Brufsky AM, Hurvitz S, Perez E, et al. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286–4293. PubMed PMID: 21990397; eng.
   PubMed Web of Science ®Google Scholar
• Miles D, Cameron D, Bondarenko I, et al. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): a double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146–155. PubMed PMID: 27817944; eng.
   PubMed Web of Science ®Google Scholar
• Starodub AN, Ocean AJ, Shah MA, et al. First-in-human trial of a novel anti-trop-2 antibody-SN-38 conjugate, sacituzumab govitecan, for the treatment of diverse metastatic solid tumors. Clin Cancer Res. 2015 Sep 1;21(17):3870–3878. PubMed PMID: 25944802; PubMed Central PMCID: PMCPMC4558321. eng.
   PubMed Web of Science ®Google Scholar
• Bardia A, Tolaney SM, Loirat D, et al. LBA17 ASCENT: a randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2020;31:S1149–S1150.
   Web of Science ®Google Scholar
• Syed BA. The breast cancer market. Nat Rev Drug Discov. 2015 Apr;14(4):233–234. . PubMed PMID: 25829273; eng.
   PubMed Web of Science ®Google Scholar
• Fortune Business Insights. Breast cancer therapeutics market size, share and industry analysis by therapy (Targeted therapy, hormonal therapy, chemotherapy), by distribution channel (Hospital pharmacies, retail pharmacies, online pharmacies), by cancer type (Hormone receptor, HER2+), and regional forecast, 2019-2026. 2020. [cited 2020 Sep 20]. Available from: https://www.fortunebusinessinsights.com/industry-reports/breast-cancer-therapeutics-market-100163.
   Google Scholar
• FutureWise Research. Triple negative breast cancer treatment market by drug type, by distribution channel, and by region: industry analysis, market share, revenue opportunity, competition and forecast 2020-2027. 2020. [cited 2020 Oct 02]. Available from: https://www.futurewiseresearch.com/healthcare-market-research/Triple-Negative-Breast/249.
   Google Scholar
• Verified Market Research. Global immunotherapy drugs market by therapy area (Cancer, autoimmune and inflammatory diseases, infectious diseases), by end user (Hospitals, clinics), by type of drug (monoclonal antibodies, adult vaccines, preventive vaccines, therapeutic vaccines, checkpoint inhibitors, interferons alpha & beta, interleukins), by geographic scope & forecast. 2020. [cited 2020 Sep 20]. Available from: https://www.verifiedmarketresearch.com/product/immunotherapy-drugs-market/.
   Google Scholar
• Partridge N, Scadding J. The James Lind Alliance: patients and clinicians should jointly identify their priorities for clinical trials. Lancet. 2004 Nov;364(9449):1923–1924. PubMed PMID: 15566996; eng.
   PubMed Web of Science ®Google Scholar
• Nixon NA, Simmons C, Lemieux J, et al. Research priorities in metastatic breast cancer: a James Lind Alliance priority setting partnership. Breast J. 2020 Mar;26(3):488–493. PubMed PMID: 31478296; eng.
   PubMed Web of Science ®Google Scholar
• Bianchini G, Balko JM, Mayer IA, et al. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016 Nov;13(11):674–690. PubMed PMID: 27184417; PubMed Central PMCID: PMCPMC5461122. eng.
   PubMed Web of Science ®Google Scholar
• 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. PubMed PMID: 27310713; PubMed Central PMCID: PMCPMC4911051. eng.
   PubMed Web of Science ®Google Scholar
• Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009 Mar 10;27(8):1160–1167. PubMed PMID: 19204204; PubMed Central PMCID: PMCPMC2667820 found at the end of this article. eng.
   PubMed Web of Science ®Google Scholar
• Burstein MD, Tsimelzon A, Poage GM, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2015 Apr 1;21(7):1688–1698. PubMed PMID: 25208879; PubMed Central PMCID: PMCPMC4362882. eng.
   PubMed Web of Science ®Google Scholar
• Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011 Jul;121(7):2750–2767. PubMed PMID: 21633166; PubMed Central PMCID: PMCPMC3127435. eng.
   PubMed Web of Science ®Google Scholar
• Vesely MD, Kershaw MH, Schreiber RD, et al. Natural innate and adaptive immunity to cancer. Annu Rev Immunol . 2011;29(1):235–271. PubMed PMID: 21219185; eng. .
   PubMed Web of Science ®Google Scholar
• Burnet M. Cancer; a biological approach. I. The processes of control. Br Med J. 1957 Apr 6;1(5022):779–786. PubMed PMID: 13404306; PubMed Central PMCID: PMCPMC1973174. eng.
   PubMed Web of Science ®Google Scholar
• Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002 Nov 3;3(11):991–998. PubMed PMID: 12407406; eng.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646–674. PubMed PMID: 21376230; eng.
   PubMed Web of Science ®Google Scholar
• Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976 Aug;116(2):180–183. PubMed PMID: 820877; eng.
   PubMed Web of Science ®Google Scholar
• Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol. 2014 Jun 15;192(12):5451–5458. PubMed PMID: 24907378; PubMed Central PMCID: PMCPMC6293462. eng.
   PubMed Web of Science ®Google Scholar
• Achkar T, Tarhini AA. The use of immunotherapy in the treatment of melanoma. J Hematol Oncol. 2017 Apr 24;10(1):88. PubMed PMID: 28434398; PubMed Central PMCID: PMCPMC5402170. eng.
   PubMedGoogle Scholar
• Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996 Mar 22;271(5256):1734–1736. PubMed PMID: 8596936; eng.
   PubMed Web of Science ®Google Scholar
• Iwai Y, Ishida M, Tanaka Y, et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12293–12297. PubMed PMID: 12218188; PubMed Central PMCID: PMCPMC129438. eng.
   PubMed Web of Science ®Google Scholar
• Ishida Y, Agata Y, Shibahara K et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. Embo J. 1992. Nov;1111:3887–3895. PubMed PMID: 1396582; PubMed Central PMCID: PMCPMC556898. eng.
   PubMed Web of Science ®Google Scholar
• Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med . 2010;363(8):711–723. PubMed PMID: 20525992; eng.
   PubMed Web of Science ®Google Scholar
• Gatti-Mays ME, Balko JM, Gameiro SR, et al. If we build it they will come: targeting the immune response to breast cancer. NPJ Breast Cancer. 2019;5(1):37. PubMed PMID: 31700993; PubMed Central PMCID: PMCPMC6820540. eng.
   PubMed Web of Science ®Google Scholar
• Denkert C, Von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018 Jan;19(1):40–50. PubMed PMID: 29233559; eng.
   PubMed Web of Science ®Google Scholar
• Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837–1846. PubMed PMID: 26970723; eng.
   PubMed Web of Science ®Google Scholar
• Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014 Apr 2;2(4):361–370. PubMed PMID: 24764583; PubMed Central PMCID: PMCPMC4000553. eng.
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443–2454. PubMed PMID: 22658127; PubMed Central PMCID: PMCPMC3544539. eng.
   PubMed Web of Science ®Google Scholar
• Barroso-Sousa R, Jain E, Cohen O, et al. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Ann Oncol. 2020 Mar;31(3):387–394. PubMed PMID: 32067680; eng.
   PubMed Web of Science ®Google Scholar
• Colli LM, Machiela MJ, Myers TA, et al. Burden of nonsynonymous mutations among TCGA cancers and candidate immune checkpoint inhibitor responses. Cancer Res. 2016 Jul 1;76(13):3767–3772. PubMed PMID: 27197178; PubMed Central PMCID: PMCPMC4930685. eng.
   PubMed Web of Science ®Google Scholar
• Adams S, Loi S, Toppmeyer D, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019 Mar 1;30(3):405–411. PubMed PMID: 30475947; eng.
   PubMed Web of Science ®Google Scholar
• Adams S, Schmid P, Rugo HS, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol. 2019 Mar 1;30(3):397–404. PubMed PMID: 30475950; eng.
   PubMed Web of Science ®Google Scholar
• Emens LA, Cruz C, Eder JP, et al. Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: a phase 1 study. JAMA Oncol. 2019 Jan 1;5(1):74–82. PubMed PMID: 30242306; eng.
   PubMed Web of Science ®Google Scholar
• Cortés J, Lipatov O, Im SA, et al. LBA21 - KEYNOTE-119: phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple negative breast cancer (mTNBC). Ann Oncol. 2019;30:v859–v860.
   PubMed Web of Science ®Google Scholar
• Lind H, Gameiro SR, Jochems C, et al. Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances. J Immunother Cancer. 2020 Feb;8(1):e000433. PubMed PMID: 32079617; PubMed Central PMCID: PMCPMC7057416. eng.
   Web of Science ®Google Scholar
• Locke G, Zhang Y, Ojalvo LS, et al. Abstract P3-09-13: identification of a tumor biomarker in advanced triple-negative breast cancer that predicts response to bintrafusp alfa (M7824), a bifunctional fusion protein targeting transforming growth factor-β and programmed death ligand 1. Cancer Res. 2020;80(4Supplement):9–13.
   Google Scholar
• Southall PJ, Boxer GM, Bagshawe KD, et al. Immunohistological distribution of 5T4 antigen in normal and malignant tissues. Br J Cancer. 1990 Jan;61(1):89–95. PubMed PMID: 2404511; PubMed Central PMCID: PMCPMC1971328. eng.
   PubMed Web of Science ®Google Scholar
• Kooshkaki O, Derakhshani A, Hosseinkhani N, et al. Combination of ipilimumab and nivolumab in cancers: from clinical practice to ongoing clinical trials. Int J Mol Sci. 2020 Jun 22;21(12):4427. PubMed PMID: 32580338; PubMed Central PMCID: PMCPMC7352976. eng.
   Web of Science ®Google Scholar
• Overdijk MB, Strumane K, Buijsse AO, et al. Abstract 2391: DR5 agonist activity of HexaBody®-DR5/DR5 (GEN1029) is potentiated by C1q and independent of Fc-gamma receptor binding in preclinical tumor models. Cancer Res. 2019;79(13 Supplement):2391.
   Web of Science ®Google Scholar
• Angata T, Tabuchi Y, Nakamura K, et al. Siglec-15: an immune system Siglec conserved throughout vertebrate evolution. Glycobiology. 2007 Aug;17(8):838–846. PubMed PMID: 17483134; eng.
   PubMed Web of Science ®Google Scholar
• Wang J, Sun J, Liu LN, et al. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat Med. 2019 Apr;25(4):656–666. PubMed PMID: 30833750; PubMed Central PMCID: PMCPMC7175920. eng.
   PubMed Web of Science ®Google Scholar
• Pob A. Siglec-15: an attractive immunotherapy target. Cancer Discov. 2020 Jan;10(1):7–8. PubMed PMID: 31806628; eng.
   Web of Science ®Google Scholar
• Nanda R, Liu MC, Yau C, 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. 2020 Feb 13;6(5):1–9. PubMed PMID: 32053137; PubMed Central PMCID: PMCPMC7058271; eng.
   Web of Science ®Google Scholar
• Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019 Aug 1;30(8):1279–1288. PubMed PMID: 31095287; eng.
   PubMed Web of Science ®Google Scholar
• Roche. Roche provides update on Phase III study of Tecentriq in combination with paclitaxel for people with metastatic triple-negative breast cancer. 2020. [cited 2020 Sept 20th]. Available from: https://www.roche.com/media/releases/med-cor-2020-08-06.htm
   Google Scholar
• Shah AN, Flaum L, Helenowski I, et al. Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2-negative endocrine-refractory metastatic breast cancer. J Immunother Cancer. 2020 Feb 8;8(1):e000173. PubMed PMID: 32060053; PubMed Central PMCID: PMCPMC7057426. eng.
   Web of Science ®Google Scholar
• Zitvogel L, Apetoh L, Ghiringhelli F, et al. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008 Jan 8;8(1):59–73. PubMed PMID: 18097448; eng.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Buqué A, Kepp O, et al. Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell. 2015 Dec 14;28(6):690–714. PubMed PMID: 26678337; eng.
   PubMed Web of Science ®Google Scholar
• Voorwerk L, Slagter M, Horlings HM, et al. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019 Jun;25(6):920–928. PubMed PMID: 31086347; eng.
   PubMed Web of Science ®Google Scholar
• Pascual J, Turner NC. Targeting the PI3-kinase pathway in triple-negative breast cancer. Ann Oncol. 2019 Jul 1;30(7):1051–1060. PubMed PMID: 31050709; eng.
   PubMed Web of Science ®Google Scholar
• Peng W, Chen JQ, Liu C, et al. Loss of PTEN promotes resistance to T Cell–Mediated Immunotherapy. Cancer Discov. 2016 Feb 6;6(2):202–216. PubMed PMID: 26645196; PubMed Central PMCID: PMCPMC4744499. eng.
   PubMed Web of Science ®Google Scholar
• George S, Miao D, Demetri GD, et al. Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity. 2017 Feb 21;46(2):197–204. PubMed PMID: 28228279; PubMed Central PMCID: PMCPMC5408320. eng.
   PubMed Web of Science ®Google Scholar
• Chandrasekaran S, Sasaki M, Scharer CD, et al. Phosphoinositide 3-Kinase signaling can modulate MHC class I and II expression. Mol Cancer Res. 2019 Dec;17(12):2395–2409. PubMed PMID: 31548239; PubMed Central PMCID: PMCPMC7339488. eng.
   PubMed Web of Science ®Google Scholar
• Crompton JG, Sukumar M, Roychoudhuri R, et al. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res. 2015 Jan 15;75(2):296–305. PubMed PMID: 25432172; PubMed Central PMCID: PMCPMC4384335. eng.
   PubMed Web of Science ®Google Scholar
• Schmid P, Loirat D, Savas P, et al. Abstract CT049: phase Ib study evaluating a triplet combination of ipatasertib (IPAT), atezolizumab (atezo), and paclitaxel (PAC) or nab-PAC as first-line (1L) therapy for locally advanced/metastatic triple-negative breast cancer (TNBC). Cancer Res. 2019;79(13Supplement):CT049–CT049.
   Google Scholar
• The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012 Oct 4;490(7418):61–70. PubMed PMID: 23000897; PubMed Central PMCID: PMCPMC3465532. eng.
   PubMed Web of Science ®Google Scholar
• Loi S, Dushyanthen S, Beavis PA, et al. RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors. Clin Cancer Res. 2016 Mar 15;22(6):1499–1509. PubMed PMID: 26515496; PubMed Central PMCID: PMCPMC4794351. eng.
   PubMed Web of Science ®Google Scholar
• Brufsky A, Kim S-B, Zvirbule Z, et al. Phase II COLET study: atezolizumab (A) + cobimetinib (C) + paclitaxel (P)/nab-paclitaxel (nP) as first-line (1L) treatment (tx) for patients (pts) with locally advanced or metastatic triple-negative breast cancer (mTNBC). J clin oncol. 2019;37(15_suppl):1013.
   Web of Science ®Google Scholar
• Pantelidou C, Sonzogni O, De Oliveria Taveira M, et al. parp inhibitor efficacy depends on CD8(+) T-cell recruitment via intratumoral sting pathway activation in BRCA-deficient models of triple-negative breast cancer. Cancer Discov. 2019 Jun 9;9(6):722–737. PubMed PMID: 31015319; PubMed Central PMCID: PMCPMC6548644. eng.
   PubMed Web of Science ®Google Scholar
• Qin G, Wang X, Ye S, et al. NPM1 upregulates the transcription of PD-L1 and suppresses T cell activity in triple-negative breast cancer. Nat Commun. 2020 Apr 3;11(1):1669. PubMed PMID: 32245950; PubMed Central PMCID: PMCPMC7125142. eng.
   PubMed Web of Science ®Google Scholar
• Vinayak S, Tolaney SM, Schwartzberg L, et al. Open-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer. JAMA Oncol. 2019 Jun 13;5(8):1132–1140. PubMed PMID: 31194225; PubMed Central PMCID: PMCPMC6567845. eng.
   PubMed Web of Science ®Google Scholar
• Domchek SM, Postel-Vinay S, Im SA, 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 Sep;21(9):1155–1164. PubMed PMID: 32771088; eng.
   PubMed Web of Science ®Google Scholar
• Schmittnaegel M, Rigamonti N, Kadioglu E, et al. Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Sci Transl Med. 2017 Apr 12;9(385):eaak9670. PubMed PMID: 28404865; eng.
   PubMed Web of Science ®Google Scholar
• Allen E, Jabouille A, Rivera LB, et al. Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation. Sci Transl Med. 2017 Apr 12;9(385):eaak9679. PubMed PMID: 28404866; PubMed Central PMCID: PMCPMC5554432. eng.
   Web of Science ®Google Scholar
• Liu J, Liu Q, Li Y, et al. Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial. J Immunother Cancer. 2020 May;8(1):e000696. PubMed PMID: 32448804; PubMed Central PMCID: PMCPMC7252975. eng.
   Web of Science ®Google Scholar
• Woo SR, Turnis ME, Goldberg MV, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012 Feb 15;72(4):917–927. PubMed PMID: 22186141; PubMed Central PMCID: PMCPMC3288154. eng.
   PubMed Web of Science ®Google Scholar
• Segal NH, He AR, Doi T, et al. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin Cancer Res. 2018 Apr 15;24(8):1816–1823. PubMed PMID: 29549159; eng.
   PubMed Web of Science ®Google Scholar
• Tolcher AW, Sznol M, Hu-Lieskovan S, et al. Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017 Sep 15;23(18):5349–5357. PubMed PMID: 28634283; eng.
   PubMed Web of Science ®Google Scholar
• Liakou CI, Kamat A, Tang DN, et al. CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14987–14992. PubMed PMID: 18818309; PubMed Central PMCID: PMCPMC2567480. eng.
   PubMed Web of Science ®Google Scholar
• Cannarile MA, Weisser M, Jacob W, et al. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. PubMed PMID: 28716061; PubMed Central PMCID: PMCPMC5514481. eng.
   PubMedGoogle Scholar
• Zhang QW, Liu L, Gong CY, et al. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS One. 2012;7(12):e50946. PubMed PMID: 23284651; PubMed Central PMCID: PMCPMC3532403. eng.
   PubMed Web of Science ®Google Scholar
• Ries CH, Cannarile MA, Hoves S, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014 Jun 16;25(6):846–859. PubMed PMID: 24898549; eng.
   PubMed Web of Science ®Google Scholar
• Schmid MC, Khan SQ, Kaneda MM, et al. Integrin CD11b activation drives anti-tumor innate immunity. Nat Commun. 2018 Dec 19;9(1):5379. PubMed PMID: 30568188; PubMed Central PMCID: PMCPMC6300665 developing LA1 for therapeutic indications. eng.
   PubMedGoogle Scholar
• Johnson DE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018 Apr;15(4):234–248. . PubMed PMID: 29405201; PubMed Central PMCID: PMCPMC5858971. eng.
   PubMed Web of Science ®Google Scholar
• Rakoff-Nahoum S, Medzhitov R. Toll-like receptors and cancer. Nat Rev Cancer. 2009 Jan 9;9(1):57–63. . PubMed PMID: 19052556; eng.
   PubMed Web of Science ®Google Scholar
• Charych D, Khalili S, Dixit V, et al. Modeling the receptor pharmacology, pharmacokinetics, and pharmacodynamics of NKTR-214, a kinetically-controlled interleukin-2 (IL2) receptor agonist for cancer immunotherapy. PLoS One. 2017;12(7):e0179431. PubMed PMID: 28678791; PubMed Central PMCID: PMCPMC5497954. eng.
   PubMed Web of Science ®Google Scholar
• Diab A, Marcondes M, Kotzin B, et al. Phase Ib: preliminary clinical activity and immune activation for NKTR-262 [TLR 7/8 agonist] plus NKTR-214 [CD122-biased agonist] in patients (pts) with locally advanced or metastatic solid tumors (REVEAL Phase Ib/II Trial). J clin oncol. 2019;37(8_suppl):26.
   Web of Science ®Google Scholar
• Leone RD, Emens LA. Targeting adenosine for cancer immunotherapy. J Immunother Cancer. 2018 Jun 18;6(1):57. . PubMed PMID: 29914571; PubMed Central PMCID: PMCPMC6006764. eng.
   PubMed Web of Science ®Google Scholar
• Huang CS, Yu AL, Tseng LM, et al. Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study. J Immunother Cancer. 2020 Jul 8;8(2):e000342. PubMed PMID: 32718986; PubMed Central PMCID: PMCPMC7380846. eng.
   Web of Science ®Google Scholar
• Toh U, Sakurai S, Saku S, et al. Early phase II study of mixed 19-peptide vaccine monotherapy for refractory triple-negative breast cancer. Cancer Sci. 2020 Jun 3;111(8):2760–2769. PubMed PMID: 32495455; eng.
   PubMed Web of Science ®Google Scholar
• Brown TA 2nd, Mittendorf EA, Hale DF, et al. Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence. Breast Cancer Res Treat. 2020 Jun;181(2):391–401. PubMed PMID: 32323103; PubMed Central PMCID: PMCPMC7188712. eng.
   PubMed Web of Science ®Google Scholar
• Qi XW, Zhang F, Yang XH, et al. High Wilms’ tumor 1 mRNA expression correlates with basal-like and ERBB2 molecular subtypes and poor prognosis of breast cancer. Oncol Rep. 2012 Oct;28(4):1231–1236. PubMed PMID: 22797561; eng.
   PubMed Web of Science ®Google Scholar
• Wylie B, Macri C, Mintern JD, et al. Dendritic Cells and Cancer: from Biology to Therapeutic Intervention. Cancers (Basel). 2019 Apr 11;11(4):521. PubMed PMID: 30979057; PubMed Central PMCID: PMCPMC6521027. eng.
   Web of Science ®Google Scholar
• Tang M, Liu Y, Zhang QC, et al. Antitumor efficacy of the Runx2-dendritic cell vaccine in triple-negative breast cancer in vitro. Oncol Lett. 2018 Sep;16(3):2813–2822. PubMed PMID: 30127867; PubMed Central PMCID: PMCPMC6096217. eng.
   PubMed Web of Science ®Google Scholar
• Avigan D, Vasir B, Gong J, et al. Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res. 2004 Jul 15;10(14):4699–4708. PubMed PMID: 15269142; eng.
   PubMed Web of Science ®Google Scholar
• Qi CJ, Ning YL, Han YS, et al. Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer. Cancer Immunol Immunother. 2012 Sep;61(9):1415–1424. PubMed PMID: 22290073; eng.
   PubMed Web of Science ®Google Scholar
• O’Shaughnessy J, Roberts LK, Smith JL, et al. Safety and initial clinical efficacy of a dendritic cell (DC) vaccine in locally advanced, triple-negative breast cancer (TNBC) patients (pts). J clin oncol. 2016;34(15_suppl):1086.
   Web of Science ®Google Scholar
• Sussman D, Smith LM, Anderson ME, et al. SGN-LIV1A: a novel antibody-drug conjugate targeting LIV-1 for the treatment of metastatic breast cancer. Mol Cancer Ther. 2014 Dec;13(12):2991–3000. PubMed PMID: 25253783; eng.
   PubMed Web of Science ®Google Scholar
• Han H, Diab S, Alemany C, et al. Abstract PD1-06: open label phase 1b/2 study of ladiratuzumab vedotin in combination with pembrolizumab for first-line treatment of patients with unresectable locally-advanced or metastatic triple-negative breast cancer. Cancer Res. 2020;80(4Supplement):1–06.
   Google Scholar
• Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, A novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res. 2016 Oct 15;22(20):5097–5108. PubMed PMID: 27026201; eng.
   PubMed Web of Science ®Google Scholar
• Modi S, Park H, Murthy RK, 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. 2020 Jun 10;38(17):1887–1896. PubMed PMID: 32058843; PubMed Central PMCID: PMCPMC7280051. eng.
   PubMed Web of Science ®Google Scholar
• Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000 Aug 17;406(6797):747–752. PubMed PMID: 10963602; eng.
   PubMed Web of Science ®Google Scholar
• Prat A, Lluch A, Albanell J, et al. Predicting response and survival in chemotherapy-treated triple-negative breast cancer. Br J Cancer. 2014 Oct 14;111(8):1532–1541. PubMed PMID: 25101563; PubMed Central PMCID: PMCPMC4200088. eng.
   PubMed Web of Science ®Google Scholar
• Balko JM, Giltnane JM, Wang K, et al. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov. 2014 Feb 4;4(2):232–245. PubMed PMID: 24356096; PubMed Central PMCID: PMCPMC3946308. eng.
   PubMed Web of Science ®Google Scholar
• Kim C, Gao R, Sei E, et al. Chemoresistance evolution in triple-negative breast cancer delineated by single-cell sequencing. Cell. 2018 May 3;173(4):879–893.e13. PubMed PMID: 29681456; PubMed Central PMCID: PMCPMC6132060. eng.
   PubMed Web of Science ®Google Scholar
• Rugo HS, Loi S, Adams S, et al. Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): post-hoc analysis of IMpassion130. Ann Oncol. 2019;30:v858–v859.
   PubMed Web of Science ®Google Scholar
• Cocco S, Piezzo M, Calabrese A, et al. Biomarkers in triple-negative breast cancer: state-of-the-art and future perspectives. Int J Mol Sci. 2020 Jun 27;21(13):4579. PubMed PMID: 32605126; PubMed Central PMCID: PMCPMC7369987. eng.
   Web of Science ®Google Scholar
• Lin NU, Claus E, Sohl J, et al. Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer. 2008 Nov 15;113(10):2638–2645. PubMed PMID: 18833576; PubMed Central PMCID: PMCPMC2835546. eng.
   PubMed Web of Science ®Google Scholar