Progress in systemic therapy for triple-negative breast cancer

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394–424

Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breastcancer. N Engl J Med 2010; 363(20): 1938–1948

Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007; 13(15): 4429–1434

Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol 2016; 13(11): 674–690

André F, Zielinski CC. Optimal strategies for the treatment of metastatic triple-negative breast cancer with currently approved agents. Ann Oncol 2012; 23(Suppl 6): vi46–vi51

Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 2019; 69(5): 363–385

Garrido-Castro AC, Lin NU, Polyak K. Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment. Cancer Discov 2019; 9(2): 176–198

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011; 121(7): 2750–2767

Denkert C, Liedtke C, Tutt A, von Minckwitz G. Molecular alterations in triple-negative breast cancer—the road to new treatment strategies. Lancet 2017; 389(10087): 2430–2442

Hu XC, Zhang J, Xu BH, Cai L, Ragaz J, Wang ZH, Wang BY, Teng YE, Tong ZS, Pan YY, Yin YM, Wu CP, Jiang ZF, Wang XJ, Lou GY, Liu DG, Feng JF, Luo JF, Sun K, Gu YJ, Wu J, Shao ZM. 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 2015; 16(4): 436–446

Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med 2018; 24(5): 628–637

Loibl S, Weber KE, Timms KM, Elkin EP, Hahnen E, Fasching PA, Lederer B, Denkert C, Schneeweiss A, Braun S, Salat CT, Rezai M, Blohmer JU, Zahm DM, Jackisch C, Gerber B, Klare P, Kümmel S, Schem C, Paepke S, Schmutzler R, Rhiem K, Penn S, Reid J, Nekljudova V, Hartman AR, von Minckwitz G, Untch M. Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto. Ann Oncol 2018; 29(12): 2341–2347

von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, Zahm DM, Kümmel S, Eidtmann H, Klare P, Huober J, Costa S, Tesch H, Hanusch C, Hilfrich J, Khandan F, Fasching PA, Sinn BV, Engels K, Mehta K, Nekljudova V, Untch M. 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

Sikov W, Berry D, Perou C, Singh B, Cirrincione C, Tolaney S, Somlo G, Port E, Qamar R, Sturtz K, Mamounas E, Golshan M, Bellon J, Collyar D, Hahn O, Carey L, Hudis C, Winer E. Abstract S2-05: Event-free and overall survival following neoadjuvant weekly paclitaxel and dose-dense AC +/− carboplatin and/or bevacizumab in triple-negative breast cancer: outcomes from CALGB 40603 (Alliance). Cancer Res 2016; 76(4 Supplement): S2–05

Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. 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 2015; 33(1): 13–21

Poggio F, Bruzzone M, Ceppi M, Pondé NF, La Valle G, Del Mastro L, de Azambuja E, Lambertini M. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis. Ann Oncol 2018; 29(7): 1497–1508

Sharma P, López-Tarruella S, García-Saenz JA, Khan QJ, Gómez HL, Prat A, Moreno F, Jerez-Gilarranz Y, Barnadas A, Picornell AC, Monte-Millán MD, González-Rivera M, Massarrah T, Pelaez-Lorenzo B, Palomero MI, González Del Val R, Cortés J, Fuentes-Rivera H, Morales DB, Márquez-Rodas I, Perou CM, Lehn C, Wang YY, Klemp JR, Mammen JV, Wagner JL, Amin AL, O’Dea AP, Heldstab J, Jensen RA, Kimler BF, Godwin AK, Martín M. Pathological response and survival in triple-negative breast cancer following neoadjuvant carboplatin plus docetaxel. Clin Cancer Res 2018; 24(23): 5820–5829

Sharma P, López-Tarruella S, García-Saenz JA, Ward C, Connor CS, Gómez HL, Prat A, Moreno F, Jerez-Gilarranz Y, Barnadas A, Picornell AC, Del Monte-Millán M, Gonzalez-Rivera M, Massarrah T, Pelaez-Lorenzo B, Palomero MI, González Del Val R, Cortes J, Fuentes Rivera H, Bretel Morales D, Márquez-Rodas I, Perou CM, Wagner JL, Mammen JM, McGinness MK, Klemp JR, Amin AL, Fabian CJ, Heldstab J, Godwin AK, Jensen RA, Kimler BF, Khan QJ, Martin M. Efficacy of neoadjuvant carboplatin plus docetaxel in triple-negative breast cancer: combined analysis oftwo cohorts. Clin Cancer Res 2017; 23(3): 649–657

Zhang P, Yin Y, Mo H, Zhang B, Wang X, Li Q, Yuan P, Wang J, Zheng S, Cai R, Ma F, Fan Y, Xu B. Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: a randomized phase 2 trial. Oncotarget 2016; 7(37): 60647–60656

Belli C, Duso BA, Ferraro E, Curigliano G. Homologous recombination deficiency in triple negative breast cancer. Breast 2019; 45: 15–21

Popova T, Manié E, Rieunier G, Caux-Moncoutier V, Tirapo C, Dubois T, Delattre O, Sigal-Zafrani B, Bollet M, Longy M, Houdayer C, Sastre-Garau X, Vincent-Salomon A, Stoppa-Lyonnet D, Stern MH. Ploidy and large-scale genomic instability consistently identify basal-like breast carcinomas with BRCA1/2 inactivation. Cancer Res 2012; 72(21): 5454–5462

Birkbak NJ, Wang ZC, Kim JY, Eklund AC, Li Q, Tian R, Bowman-Colin C, Li Y, Greene-Colozzi A, Iglehart JD, Tung N, Ryan PD, Garber JE, Silver DP, Szallasi Z, Richardson AL. Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents. Cancer Discov 2012; 2(4): 366–375

Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, Szallasi Z, Barry WT, Winer EP, Tung NM, Isakoff SJ, Ryan PD, Greene-Colozzi A, Gutin A, Sangale Z, Iliev D, Neff C, Abkevich V, Jones JT, Lanchbury JS, Hartman AR, Garber JE, Ford JM, Silver DP, Richardson AL. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin Cancer Res 2016; 22(15): 3764–3773

Minckwitz GV, Timms K, Untch M, Elkin EP, Fasching PA, Schneeweiss A, Salat C, Rezai M, Blohmer JU, Zahm DM, Jackisch C, Gerber B, Klare P, Kümmel S, Eidtmann H, Paepke S, Reid JE, Nekljudova V, Hartman A-R, Loibl S. 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 2015; 33 (15_suppl): 1004

Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, Rugo HS, Liu MC, Stearns V, Come SE, Timms KM, Hartman AR, Borger DR, Finkelstein DM, Garber JE, Ryan PD, Winer EP, Goss PE, Ellisen LW. TBCRC009: a multicenter phase II clinical trial of platinum monotherapy with biomarker assessment in metastatic triple-negative breast cancer. J Clin Oncol 2015; 33(17): 1902–1909

Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009; 27(8): 1160–1167

Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist 2011; 16(Suppl 1): 61–70

Perou CM, S0rlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Børresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature 2000; 406(6797): 747–752

Prat A, Lluch A, Albanell J, Barry WT, Fan C, Chacón JI, Parker JS, Calvo L, Plazaola A, Arcusa A, Seguí-Palmer MA, Burgues O, Ribelles N, Rodriguez-Lescure A, Guerrero A, Ruiz-Borrego M, Munarriz B, López JA, Adamo B, Cheang MC, Li Y, Hu Z, Gulley ML, Vidal MJ, Pitcher BN, Liu MC, Citron ML, Ellis MJ, Mardis E, Vickery T, Hudis CA, Winer EP, Carey LA, Caballero R, Carrasco E, Martín M, Perou CM, Alba E. Predicting response and survival in chemotherapy-treated triple-negative breast cancer. Br J Cancer 2014; 111(8): 1532–1541

Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010; 12(5): R68

Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, Rasmussen KE, Jones LP, Assefnia S, Chandrasekharan S, Backlund MG, Yin Y, Khramtsov AI, Bastein R, Quackenbush J, Glazer RI, Brown PH, Green JE, Kopelovich L, Furth PA, Palazzo JP, Olopade OI, Bernard PS, Churchill GA, Van Dyke T, Perou CM. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol 2007; 8(5): R76

Bruna A, Greenwood W, Le Quesne J, Teschendorff A, Miranda-Saavedra D, Rueda OM, Sandoval JL, Vidakovic AT, Saadi A, Pharoah P, Stingl J, Caldas C. TGFβ induces the formation of tumour-initiating cells in claudinlow breast cancer. Nat Commun 2012; 3(1): 1055

Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, Sanders M, Stanford J, Cook RS, Arteaga CL. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Invest 2013; 123(3): 1348–1358

Starodub AN, Ocean AJ, Shah MA, Guarino MJ, Picozzi VJ Jr, Vahdat LT, Thomas SS, Govindan SV, Maliakal PP, Wegener WA, Hamburger SA, Sharkey RM, Goldenberg DM. 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; 21(17): 3870–3878

Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O’Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med 2019; 380(8): 741–751

Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget 2015; 6(26): 22496–22512

Keir CH, Vahdat LT. The use of an antibody drug conjugate, glembatumumab vedotin (CDX-011), for the treatment of breast cancer. Expert Opin Biol Ther 2012; 12(2): 259–263

Yardley DA, Weaver R, Melisko ME, Saleh MN, Arena FP, Forero A, Cigler T, Stopeck A, Citrin D, Oliff I, Bechhold R, Loutfi R, Garcia AA, Cruickshank S, Crowley E, Green J, Hawthorne T, Yellin MJ, Davis TA, Vahdat LT. EMERGE: a randomized phase ii study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB-expressing breast cancer. J Clin Oncol 2015; 33(14): 1609–1619

Vahdat L, Forero-Torres A, Schmid P, Blackwell K, Telli M, Melisko M, Holgado E, Moebus V, Cortes J, Fehrenbacher L, Montero A, Ma C, Nanda R, Wright G, He Y, Bagley R, Halim A, Turner C, Yardley D. Abstract P6-20-01: METRIC: A randomized international phase 2b study of the antibody-drug conjugate (ADC) glembatumumab vedotin (GV) in gpNMB-overexpressing, meta-static, triple-negative breast cancer (mTNBC). Cancer Res 2019; 79 (4 Supplement): P6–20–01

Modi S, Pusztai L, Forero A, Mita M, Miller K, Weise A, Krop I, Burris H, Kalinsky K, Tsai M, Liu M, Hurvitz S, Wilks S, Ademuyiwa F, Diab S, Han H, Kato G, Nanda R, O’Shaughnessy J, Kostic A, Li M, Specht J. 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 2018; 78(4 Supplement): PD3–14

Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and nabpaclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018; 379(22): 2108–2121

Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, Boccia R, Lippman ME, Somer R, Smakal M, Emens LA, Hrinczenko B, Edenfield W, Gurtler J, von Heydebreck A, Grote HJ, Chin K, Hamilton EP. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat 2018; 167(3): 671–686

Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, Hui R, Curigliano G, Toppmeyer D, O’Shaughnessy J, Loi S, Paluch-Shimon S, Tan AR, Card D, Zhao J, Karantza V, Cortés J. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol 2019; 30(3): 397–404

MERCK’s KEYNOTE-119 Study Press release. Merck provides update on phase 3 KEYNOTE-119 study of KEYTRUDA® (pembrolizumab) monotherapy in previously-treated patients with metastatic triple-negative breast cancer. 2019. https://investors.merck.com/news/press-release-details/2019/Merck-Provides-Update-on-Phase-3-KEYNOTE-119-Study-of-KEYTRUDA-pembrolizumab-Monotherapy-in-Previously-Treated-Patients-with-Metastatic-Triple-Negative-Breast-Cancer/default.aspx

Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 Study. J Clin Oncol 2016; 34(21): 2460–2467

Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan AR, Jia L, Ding Y, Karantza V, Schmid P. 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; 30 (3): 405–411

Tolaney S, Kalinsky K, Kaklamani V, Savulsky C, Olivo M, Aktan G, Kaufman P, Xing D, Almonte A, Misir S, Karantza V, Diab S. Abstract PD6-13: Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. Cancer Res 2018; 78(4 Supplement): PD6–13

Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, Nederlof I, Kluin RJC, Warren S, Ong S, Wiersma TG, Russell NS, Lalezari F, Schouten PC, Bakker NAM, Ketelaars SLC, Peters D, Lange CAH, van Werkhoven E, van Tinteren H, Mandjes IAM, Kemper I, Onderwater S, Chalabi M, Wilgenhof S, Haanen JBAG, Salgado R, de Visser KE, Sonke GS, Wessels LFA, Linn SC, Schumacher TN, Blank CU, Kok M. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med 2019; 25(6): 920–928

Emens LA, Cruz C, Eder JP, Braiteh F, Chung C, Tolaney SM, Kuter I, Nanda R, Cassier PA, Delord JP, Gordon MS, ElGabry E, Chang CW, Sarkar I, Grossman W, O’Hear C, Fasso M, Molinero L, Schmid P. 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; 5(1): 74–82

Jin J, Wu X, Yin J, Li M, Shen J, Li J, Zhao Y, Zhao Q, Wu J, Wen Q, Cho CH, Yi T, Xiao Z, Qu L. Identification of genetic mutations in cancer: challenge and opportunity in the new era of targeted therapy. Front Oncol 2019; 9: 263

Emens L, Loi S, Rugo H, Schneeweiss A, Dieras V, Iwata H, Barrios C, Nechaeva M, Molinero L, Nguyen Duc A, Funke R, Chui S, Husain A, Winer E, Adams S, Schmid P. Abstract GS1-04: IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer. Cancer Research 2019;79(4 Supplement):GS1–04

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375(19): 1823–1833

Loi S, Schmid P, Cortés J, Park Y, Muñoz-Couselo E, Kim S-B, Sohn J, Im S-A, Holgado E, Foukakis T, Kuemmel S, Dent R, Wang A, Aktan G, Karantza V, Salgado R. Abstract P3-10-09: Relationship between tumor infiltrating lymphocytes (TILs) and response to pembrolizumab (Pembro)+ chemotherapy (Chemo) as neoadjuvant treatment (NAT) for triple-negative breast cancer (TNBC): phase Ib KEYNOTE-173 trial. Cancer Res 2019; 79(4 Supplement): P3–10–09

Hendrickx W, Simeone I, Anjum S, Mokrab Y, Bertucci F, Finetti P, Curigliano G, Seliger B, Cerulo L, Tomei S, Delogu LG, Maccalli C, Wang E, Miller LD, Marincola FM, Ceccarelli M, Bedognetti D. Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis. OncoImmunology 2017; 6(2): e1253654

Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan CW, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D’Angelo SP, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51 (2): 202–206

Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372 (26): 2509–2520

Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490(7418): 61–70

Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. 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; 30(4): 558–566

Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017; 377 (6): 523–533

Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 2018; 379(8): 753–763

Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA 3rd, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med 2019; 381(25): 2403–2415

González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O’Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2019; 381(25): 2391–2402

Vinayak S, Tolaney SM, Schwartzberg L, Mita M, McCann G, Tan AR, Wahner-Hendrickson AE, Forero A, Anders C, Wulf GM, Dillon P, Lynce F, Zarwan C, Erban JK, Zhou Y, Buerstatte N, Graham JR, Arora S, Dezube BJ, Telli ML. Open-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer. JAMA Oncol 2019; 5(8): 1132

Domchek S, Postel-Vinay S, Im S-A, Hee Park Y, Delord J-P, Italiano A, Alexandre J, You B, Bastian S, Krebs M, Waqar S, Lanasa M, Angell H, Tang M, Gresty C, Opincar L, Herbolsheimer P, Kaufman B. Abstract PD5-04: An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): updated results in patients with germline BRCA-mutated metastatic breast cancer. Cancer Res 2019; 79(4 Supplement): PD5–04

Pascual J, Turner NC. Targeting the PI3-kinase pathway in triple-negative breast cancer. Ann Oncol 2019; 30(7): 1051–1060

Maira SM, Pecchi S, Huang A, Burger M, Knapp M, Sterker D, Schnell C, Guthy D, Nagel T, Wiesmann M, Brachmann S, Fritsch C, Dorsch M, Chène P, Shoemaker K, De Pover A, Menezes D, Martiny-Baron G, Fabbro D, Wilson CJ, Schlegel R, Hofmann F, García-Echeverría C, Sellers WR, Voliva CF. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther 2012; 11(2): 317–328

Martín M, Chan A, Dirix L, O’Shaughnessy J, Hegg R, Manikhas A, Shtivelband M, Krivorotko P, Batista López N, Campone M, Ruiz Borrego M, Khan QJ, Beck JT, Ramos Vázquez M, Urban P, Goteti S, Di Tomaso E, Massacesi C, Delaloge S. A randomized adaptive phase II/III study of buparlisib, a pan-class IPI3K inhibitor, combined with paclitaxel for the treatment of HER2-advanced breast cancer (BELLE-4). Ann Oncol 2017; 28(2): 313–320

Kim SB, Dent R, Im SA, Espié M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, Kapp AV, Chan WY, Singel SM, Maslyar DJ, Baselga J; LOTUS investigators. 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 2017; 18(10): 1360–1372

Oliveira M, Saura C, Nuciforo P, Calvo I, Andersen J, Passos-Coelho JL, Gil Gil M, Bermejo B, Patt DA, Ciruelos E, de la Peña L, Xu N, Wongchenko M, Shi Z, Singel SM, Isakoff SJ. FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer. Ann Oncol 2019; 30(8): 1289–1297

Schmid P, Abraham J, Chan S, Wheatley D, Brunt M, Nemsadze G, Baird R, Park YH, Hall P, Perren T, Stein RC, László M, Ferrero J-M, Phillips M, Conibear J, Sarker S-J, Prendergast A, Cartwright H, Mousa K, Turner NC. AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): a randomised, double-blind, placebo-controlled, phase II trial. J Clin Oncol 2018; 36(15_suppl): 1007