Therapies for triple negative breast cancer

Expert Opinion on Pharmacotherapy

Volumn 16, Issue 7, 2015, Pages 983-998

  Andreopoulou, Eleni ^a   Schweber, Sarah J ^a   Sparano, Joseph A ^a   Mcdaid, Hayley M ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Basal like breast cancer; BRCA mutations; Phosphatidylinositide 3 kinase pathway; Platinums; Poly(ADP ribose)polymerase inhibitor; Triple negative breast cancer

Indexed keywords

ANDROGEN RECEPTOR ANTAGONIST; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; BEVACIZUMAB; BICALUTAMIDE; CARBOPLATIN; CETUXIMAB; CHECKPOINT KINASE 1 INHIBITOR; CISPLATIN; CYTOTOXIC AGENT; ENTINOSTAT; ENZALUTAMIDE; ERLOTINIB; GANETESPIB; HISTONE DEACETYLASE INHIBITOR; IMMUNOMODULATING AGENT; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; OLAPARIB; PACLITAXEL; PANITUMUMAB; PAZOPANIB; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B INHIBITOR; SUNITINIB; TRAMETINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VELIPARIB; VORINOSTAT; TUBULIN MODULATOR;

ANGIOGENESIS; APOPTOSIS; CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER CLASSIFICATION; CANCER RECURRENCE; CANCER STAGING; CANCER SURVIVAL; CELL CYCLE PROGRESSION; CELL PROLIFERATION; DNA REPAIR; DRUG MECHANISM; DRUG TARGETING; EXPERIMENTAL THERAPY; GENE EXPRESSION; GERMLINE MUTATION; HIGH RISK PATIENT; HUMAN; IMMUNOMODULATION; METASTASIS; MOLECULARLY TARGETED THERAPY; NEXT GENERATION SEQUENCING; ONCOGENE; PATIENT SELECTION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENCE RISK; REVIEW; RISK ASSESSMENT; STUDY DESIGN; TREATMENT RESPONSE; TRIPLE NEGATIVE BREAST CANCER; TUMOR INVASION; TUMOR VOLUME; DRUG RESISTANCE; GENETICS; PATHOLOGY; TRIPLE NEGATIVE BREAST NEOPLASMS;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DRUG RESISTANCE, NEOPLASM; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM METASTASIS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TRIPLE NEGATIVE BREAST NEOPLASMS; TUBULIN MODULATORS;

EID: 84928521991     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2015.1032246     Document Type: Review

References (112)

1. Bauer KR, Brown M, Cress RD, et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triplenegative phenotype: a population-based study from the California cancer Registry. Cancer 2007;109(9):1721-8
2. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 2010;134(7):e48-72
3. Brown M, Tsodikov A, Bauer KR, et al. The role of human epidermal growth factor receptor 2 in the survival of women with estrogen and progesterone receptor-negative, invasive breast cancer: the California Cancer Registry, 1999-2004. Cancer 2008;112(4):737-47
4. Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004;10(16):5367-74
5. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000;406(6797):747-52
6. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13(15 Pt 1):4429-34
7. Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-Term survival in patients with triplenegative breast cancer. J Clin Oncol 2008;26(8):1275-81
8. Smid M, Wang Y, Zhang Y, et al. Subtypes of breast cancer show preferential site of relapse. Cancer Res 2008;68(9):3108-14
9. Lakhani SR, Van De Vijver MJ, Jacquemier J, et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 2002;20(9):2310-18
10. Turner NC, Reis-Filho JS, Russell AM, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene 2007;26(14):2126-32
11. Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer 2004;4(10):814-19
12. Chen X, Iliopoulos D, Zhang Q, et al. XBP1 promotes triple-negative breast cancer by controlling the HIF1alpha pathway. Nature 2014;508(7494):103-7
13. 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;121(7):2750-67
14. Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol 2011;5(1):5-23
15. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001;98(19):10869-74
16. Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009;27(8):1160-7
17. Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009;361(2):123-34
18. Kriege M, Seynaeve C, Meijers-Heijboer H, et al. Sensitivity to first-line chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2009;27(23):3764-71
19. Kriege M, Jager A, Hooning MJ, et al. The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers. Cancer 2012;118(4):899-907
20. Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010;12(5):R68
21. Creighton CJ, Li X, Landis M, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 2009;106(33):13820-5
22. Cancer Genome Atlas N. Comprehensive molecular portraits of human breast tumours. Nature 2012;490(7418):61-70
23. Shah SP, Roth A, Goya R, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 2012;486(7403):395-9
24. Banerji S, Cibulskis K, Rangel-Escareno C, et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 2012;486(7403):405-9
25. Andre F, Bachelot T, Commo F, et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/ UNICANCER). Lancet Oncol 2014;15(3):267-74
26. Dawood S, Broglio K, Gonzalez-Angulo AM, et al. Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol 2008;26(30):4891-8
27. Availablr from http://www.nccn.org
28. Gianni L, Norton L, Wolmark N, et al. Role of anthracyclines in the treatment of early breast cancer. J Clin Oncol 2009;27(28):4798-808
29. Hayes DF, Thor AD, Dressler LG, et al. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 2007;357(15):1496-506
30. R P The worldwide overview: provisional results of updated (2005-2006) meta-Analyses of trials. Proceeding from the San Antonio meeting, Eleni. Breast Cancer Res Treat 2007;106:S1
31. Hugh J, Hanson J, Cheang MC, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol 2009;27(8):1168-76
32. Jones S, Holmes FA, O'Shaughnessy J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US oncology research trial 9735. J Clin Oncol 2009;27(8):1177-83
33. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008;358(16):1663-71
34. 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;25(33):5210-17
35. Twelves C, Cortes J, Vahdat LT, et al. Phase III trials of eribulin mesylate (E7389) in extensively pretreated patients with locally recurrent or metastatic breast cancer. Clin Breast Cancer 2010;10(2):160-3
36. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and longterm clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384(9938):164-72
37. Gonzalez-Angulo AM, Timms KM, Liu S, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res 2011;17(5):1082-9
38. Hurley J, Reis IM, Rodgers SE, et al. The use of neoadjuvant platinum-based chemotherapy in locally advanced breast cancer that is triple negative: retrospective analysis of 144 patients. Breast Cancer Res Treat 2013;138(3):783-94
39. Prowell TM, Pazdur R. Pathological complete response and accelerated drug approval in early breast cancer. N Engl J Med 2012;366(26):2438-41
40. Rugo HS, Olopade O, DeMichele A, et al. Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: First efficacy results from the I-SPY 2 TRIAL[abstract S5-02]. Presented at: the 36th Annual San Antonio Breast Cancer Symposium; 10-14 December; San Antonio, TX 41. Gronwald J, Byrski T, Huzarski T, et al. Neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. J Clin Oncol (Meeting Abstracts) 2009;27(15 Suppl):abstract502
41. Silver DP, Richardson AL, Eklund AC, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol 2010;28(7):1145-53
42. Telli M. Optimizing chemotherapy in triple-negative breast cancer: the role of platinum. Am Soc Clin Oncol Educ Book 2014;e37-42
43. von Minckwitz G, Schneeweiss A, Loibl S, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 2014;15(7):747-56
44. Sikov WM, Berry DA, Perou CM, et al. Impact of the addition of carboplatin (Cb) and/or bevacizumab (B) to neoadjuvant weekly paclitaxel (P) followed by dose-dense AC on pathologic complete response (pCR) rates in triplenegative breast cancer (TNBC): CALGB 40603 (Alliance) [abstract S5-01]. San Antonio Breast Cancer Symposium; 10-14 December 2013
45. Balko JM, Cook RS, Vaught DB, et al. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nat Med 2012;18(7):1052-9
46. Yoshida T, Ozawa Y, Kimura T, et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelialmesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer 2014;110(6):1497-505
47. Hu J, Horwitz SB, McDaid HM. Abstract B165: the antitumor efficacy of eribulin is mediated via suppression of invasion and profound induction of cell death in triple negative breast cancer. Mol Cancer Ther 2013;12(11 Suppl):B165
48. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100(1):57-70
49. von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012;30(15):1796-804
50. Buchholz TA, Hill BS, Tucker SL, et al. Factors predictive of outcome in patients with breast cancer refractory to neoadjuvant chemotherapy. Cancer J 2001;7(5):413-20
51. Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25(28):4414-22
52. Dwadasi S TY, Walsh T, Danso MA, et al. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple-negative breast cancer (TNBC): Hoosier Oncology Group BRE09-146. J Clin Oncol 2014;32(5 Suppl):abstract1019
53. Chen X, Li J, Gray WH, et al. TNBCtype: a subtyping tool for triplenegative breast cancer. Cancer Inform 2012;11:147-56
54. Livasy CA, Karaca G, Nanda R, et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006;19(2):264-71
55. Carey LA, Rugo HS, Marcom PK, et al. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol 2012;30(21):2615-23
56. O'Shaughnessy J WD, Vukelja SJ, McIntyre K, et al. Preliminary results of a randomized phase II study of weekly irinotecan/carboplatin with or without cetuximab in patients with metastatic breast cancer [abstract 308]. Breast Cancer Res Treat 2007;106(Suppl 1):S32
57. Baselga J, Gomez P, Greil R, et al. Randomized phase II study of the antiepidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer. J Clin Oncol 2013;31(20):2586-92
58. Dickler MN, Cobleigh MA, Miller KD, et al. Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat 2009;115(1):115-21
59. Gutteridge E, Agrawal A, Nicholson R, et al. The effects of gefitinib in tamoxifen-resistant and hormoneinsensitive breast cancer: a phase II study. Int J Cancer 2010;126(8):1806-16
60. Miller K, Wang M, Gralow J, et al. Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer. N Engl J Med 2007;357(26):2666-76
61. 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;28(20):3239-47
62. Robert NJ, Dieras 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;29(10):1252-60
63. Miles DW, Dieras V, Cortes J, et al. First-line bevacizumab in combination with chemotherapy for HER2-negative metastatic breast cancer: pooled and subgroup analyses of data from 2447 patients. Ann Oncol 2013;24(11):2773-80
64. Burstein HJ, Elias AD, Rugo HS, et al. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2008;26(11):1810-16
65. Crown JP, Dieras V, Staroslawska E, et al. Phase III trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer. J Clin Oncol 2013;31(23):2870-8
66. von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 2012;366(4):299-309
67. Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med 2012;366(4):310-20
68. Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol 2013;14(10):933-42
69. Ame JC, Spenlehauer C, de Murcia G. The PARP superfamily. BioEssays 2004;26(8):882-93
70. Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADPribose) polymerase. Nature 2005;434(7035):913-17
71. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005;434(7035):917-21
72. Ratnam K, Low JA. Current development of clinical inhibitors of poly (ADP-ribose) polymerase in oncology. Clin Cancer Res 2007;13(5):1383-8
73. O'Shaughnessy J, Osborne C, Pippen JE, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 2011;364(3):205-14
74. O'Shaughnessy J SL, Danso MA. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J Clin Oncol 2011;29(Suppl):abstract 1007
75. Liu X, Shi Y, Maag DX, et al. Iniparib nonselectively modifies cysteinecontaining proteins in tumor cells and is not a bona fide PARP inhibitor. Clin Cancer Res 2012;18(2):510-23
76. Patel AG, De Lorenzo SB, Flatten KS, et al. Failure of iniparib to inhibit poly (ADP-Ribose) polymerase in vitro. Clin Cancer Res 2012;18(6):1655-62
77. Tutt A, Robson M, Garber JE, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 2010;376(9737):235-44
78. Gelmon KA, Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol 2011;12(9):852-61
79. Kinders R, Parchment RE, Ji J, et al. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. Mol Interv 2007;7(6):325-34
80. Isakoff SJ OB, Tung NM, Gelman RM, et al. A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer. J Clin Oncol 2010;28(15 Suppl):abstract 1019
81. Doane AS, Danso M, Lal P, et al. An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 2006;25(28):3994-4008
82. Gucalp A, Tolaney S, Isakoff SJ, et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res 2013;19(19):5505-12
83. Keen JC, Yan L, Mack KM, et al. A novel histone deacetylase inhibitor, scriptaid, enhances expression of functional estrogen receptor alpha (ER) in ER negative human breast cancer cells in combination with 5-Aza 2'-deoxycytidine. Breast Cancer Res Treat 2003;81(3):177-86
84. Tate CR, Rhodes LV, Segar HC, et al. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res 2012;14(3):R79
85. Connolly RM, Jeter S, Zorzi J, et al. A multi-institutional double-blind phase II study evaluating response and surrogate biomarkers to carboplatin and nab-paclitaxel (CP) with or without vorinostat as preoperative systemic therapy (PST) in HER2-negative primary operable breast cancer (TBCRC008). J Clin Oncol 2010;28(15 Suppl):abstractTPS111
86. Marty B, Maire V, Gravier E, et al. Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells. Breast Cancer Res 2008;10(6):R101
87. Yunokawa M, Koizumi F, Kitamura Y, et al. Efficacy of everolimus, a novel mTOR inhibitor, against basal-like triple-negative breast cancer cells. Cancer Sci 2012;103(9):1665-71
88. Juvekar A, Burga LN, Hu H, et al. Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer. Cancer Discov 2012;2(11):1048-63
89. Ibrahim YH, Garcia-Garcia C, Serra V, et al. PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition. Cancer Discov 2012;2(11):1036-47
90. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012;366(6):520-9
91. Gonzalez-Angulo AM, Akcakanat A, Liu S, et al. Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancerdagger. Ann Oncol 2014;25(6):1122-7
92. Singh JC, Stein S, Volm M, et al. RAD001-carboplatin combination in triple-negative metastatic breast cancer (TNMBC): A phase II trial. J Clin Oncol 2013;31(Suppl):abstract1042
93. NCT01629615 SAToBaPKIiPWTNMBCCgi
94. NCT01300962 LSoBoBaCiPWMBCCgi
95. Hoeflich KP, O'Brien C, Boyd Z, et al. In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin Cancer Res 2009;15(14):4649-64
96. Johnson LG AK, Duncan JS, Whittle M, et al. Kinome reprogramming response to MEK inhibition: a window-of-opportunity trial in triple-negative breast cancer (TNBC). J Clin Oncol 2013;31(Suppl):abstract 512
97. Duncan JS, Whittle MC, Nakamura K, et al. Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer. Cell 2012;149(2):307-21
98. Mirzoeva OK, Das D, Heiser LM, et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res 2009;69(2):565-72
99. Roberts PJ, Usary JE, Darr DB, et al. Combined PI3K/mTOR and MEK inhibition provides broad antitumor activity in faithful murine cancer models. Clin Cancer Res 2012;18(19):5290-303
100. Engelman JA, Chen L, Tan X, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008;14(12):1351-6
101. Legrier ME, Yang CP, Yan HG, et al. Targeting protein translation in human non small cell lung cancer via combined MEK and mammalian target of rapamycin suppression. Cancer Res 2007;67(23):11300-8
102. Schweber SJ, Rodriguez-LaRocca AG, Calvert V, et al. Protein pathway activation mapping guided biomarker development to identify optimal combinations ofMEK inhibitor with PI3K/mTOR pathway inhibitors for the treatment of triplenegative breast cancer. J Clin Oncol 2013;31(Suppl):abstract 2612
103. Chen MS, Ryan CE, Piwnica-Worms H. Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol Cell Biol 2003;23(21):7488-97
104. Ma CX, Cai S, Li S, et al. Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models. J Clin Invest 2012;122(4):1541-52
105. Loi S, Sirtaine N, Piette F, et al. Prognostic and predictive value of tumorinfiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol 2013;31(7):860-7
106. Adams S, Gray RJ, Demaria S, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol 2014;32(27):2959-66
107. Denkert C LS, Salat C, et al. Increased tumor-Associated lymphocytes predicts benefit from addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer in the GeparSixto trial (GBG 66/AGO-B) [abstract S1-06]. 2013 San Antonio Breast Cancer Symposium; Presented 11 December 2013
108. Vinayak S GR, Adams S, Jensen KC, et al. Association of increased tumor-infiltrating lymphocytes (TILs) with immunomodulatory (IM) triple-negative breast cancer (TNBC) subtype and response to neoadjuvant platinum-based therapy in PrECOG0105. J Clin Oncol 2014;32(5 Suppl):abstract 1000^
109. Stagg J, Allard B. Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects. Ther Adv Med Oncol 2013;5(3):169-81
110. 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;366(26):2443-54
111. Soliman H, Khalil F, Antonia S. PD-L1 expression is increased in a subset of basal type breast cancer cells. PLoS One 2014;9(2):e88557
112. Basu GD, Ghazalpour A, Gatalica Z, et al. Expression of novel immunotherapeutic targets in triplenegative breast cancer. J Clin Oncol 2014;32(5 Suppl):abstract 1001