Top

Published in:

01-07-2017 | Review Article

Advances in systemic therapy for metastatic breast cancer: future perspectives

Authors: S. P. Corona, N. Sobhani, A. Ianza, G. Roviello, G. Mustacchi, M. Bortul, F. Zanconati, D. Generali

Published in: Medical Oncology | Issue 7/2017

Abstract

Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease. The advent of laboratory technologies in the clinical setting such as the routine use of next generation sequencing has allowed identification of new genetic alterations as well as providing a precise picture of the molecular landscapes of each tumour. Consequently, new specific therapeutic approaches are becoming available to minimise or delay the occurrence of resistance. In this review, we analyse the latest research and news from the clinical development side for each BC subtype.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA. Cancer J Clin. 2016. http://www.ncbi.nlm.nih.gov/pubmed/28055103.

Klijn JG, Blamey RW, Boccardo F, Tominaga T, Duchateau L, Sylvester R, et al. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol. 2001;19:343–53. http://www.ncbi.nlm.nih.gov/pubmed/11208825.

Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. Comprehensive molecular portraits of human breast tumours. Nature. Nature Research; 2012;490:61–70. http://www.nature.com/doifinder/10.1038/nature11412.

Dunnwald LK, Rossing M, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res. 2007;9:R6. http://www.ncbi.nlm.nih.gov/pubmed/17239243.

Buzdar AU. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the international letrozole breast cancer group. J Clin Oncol. 2004;22:3199-200-1. http://www.jco.org/cgi/doi/10.1200/JCO.2004.99.058.

Dalmau E, Armengol-Alonso A, Muñoz M, Seguí-Palmer MÁ. Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer. The Breast. 2014;23:710–20. http://www.ncbi.nlm.nih.gov/pubmed/25311296.

Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med. 2011; 62:233–47. http://www.ncbi.nlm.nih.gov/pubmed/20887199.

Miller TW, Hennessy BT, González-Angulo AM, Fox EM, Mills GB, Chen H, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor–positive human breast cancer. J Clin Invest. 2010;120:2406–13. http://www.ncbi.nlm.nih.gov/pubmed/20530877.

Paplomata E, O’Regan R. The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers. Ther Adv Med Oncol. 2014;6:154–66. http://www.ncbi.nlm.nih.gov/pubmed/25057302.

10.

deGraffenried LA, Friedrichs WE, Russell DH, Donzis EJ, Middleton AK, Silva JM, et al. Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt activity. Clin Cancer Res. 2004;10:8059–67. http://www.ncbi.nlm.nih.gov/pubmed/15585641.

11.

Bhattacharvva GS, Biswas J, Singh JK, Singh M, Govindbabu K, Ranade AA, et al. Reversal of tamoxifen resistance (hormone resistance) by addition of sirolimus (mTOR inhibitor) in metastatic breast cancer. Eur J Cancer. 2011;47:9. http://linkinghub.elsevier.com/retrieve/pii/S0959804911701150.

12.

Generali D, Fox SB, Brizzi MP, Allevi G, Bonardi S, Aguggini S, et al. Down-regulation of phosphatidylinositol 3′-Kinase/AKT/molecular target of rapamycin metabolic pathway by primary letrozole-based therapy in human breast cancer. Clin Cancer Res. 2008;May 1;14(9):2673-80CrossRefPubMed

13.

Liao JK, Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature. 2000;407:538–41. http://www.ncbi.nlm.nih.gov/pubmed/11029009.

14.

Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo W-L, Davies M, et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT Mutations in breast cancer. Cancer Res. 2008;68:6084–91. http://www.ncbi.nlm.nih.gov/pubmed/18676830.

15.

Creighton CJ, Fu X, Hennessy BT, Casa AJ, Zhang Y, Gonzalez-Angulo AM, et al. Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res. 2010;12:R40. http://www.ncbi.nlm.nih.gov/pubmed/20569503.

16.

Fu X, Osborne CK, Schiff R. Biology and therapeutic potential of PI3K signaling in ER+/HER2-negative breast cancer. The Breast. 2013; 22:S12–8. http://www.ncbi.nlm.nih.gov/pubmed/24011769.

17.

Baselga J, Campone M, Piccart M, Burris HA, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Engl J Med. 2012;366:520–9. http://www.nejm.org/doi/10.1056/NEJMoa1109653.

18.

Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2. Ann Oncol. 2014;25:2357–62. http://www.ncbi.nlm.nih.gov/pubmed/25231953.

19.

Hortobagyi GN, Piccart-Gebhart MJ, Burris HA, Campone M, Noguchi S, Perez AT, et al. Correlation of molecular alterations with efficacy of everolimus in hormone-receptor-positive, HER2-negative advanced breast cancer: Results from BOLERO-2. J Clin Oncol. 2013;31:142. http://www.ncbi.nlm.nih.gov/pubmed/28136528.

20.

Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S, et al. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016;17:811–21. http://linkinghub.elsevier.com/retrieve/pii/S1470204516001066.

21.

Krop I, Johnston S, Mayer IA, Dickler M, Ganju V, Forero-Torres A, et al. Abstract S2-02: The FERGI phase II study of the PI3K inhibitor pictilisib (GDC-0941) plus fulvestrant vs fulvestrant plus placebo in patients with ER+ , aromatase inhibitor (AI)-resistant advanced or metastatic breast cancer—Part I results. Cancer Res. 2015;75:S2-2-S2-2. http://cancerres.aacrjournals.org/lookup/doi/10.1158/1538-7445.SABCS14-S2-02.

22.

Baselga J, Im S-A, Iwata H, Clemons M, Ito Y, Awada A, et al. PIK3CA status in circulating tumor DNA predicts efficacy of buparlisib plus fulvestrant in postmenopausal women with endocrine-resistant HR+/HER2—advanced breast cancer: first results from the randomized, Phase III BELLE-2 Trial. Emmanuelle Di Tomaso. Patrick Urban; 2015;18.

23.

Juric D, Rodon J, Gonzalez-Angulo AM, Burris HA, Bendell J, Berlin JD, et al. Abstract CT-01: BYL719, a next generation PI3K alpha specific inhibitor: preliminary safety, PK, and efficacy results from the first-in-human study. Cancer Res. 2014;72.

24.

Shah OJ, Wang Z, Hunter T. Inappropriate activation of the TSC/Rheb/mTOR/S6 K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr Biol. 2004;14:1650–6. http://www.ncbi.nlm.nih.gov/pubmed/15380067.

25.

Dowling RJ, Niraula S, Chang MC, Done SJ, Ennis M, McCready DR, et al. Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res. 2015;17:32. http://www.ncbi.nlm.nih.gov/pubmed/25849721.

26.

Bonanni B, Puntoni M, Cazzaniga M, Pruneri G, Serrano D, Guerrieri-Gonzaga A, et al. Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial. J Clin Oncol. 2012;30:2593–600. http://www.ncbi.nlm.nih.gov/pubmed/22564993.

27.

Cazzaniga M, DeCensi A, Pruneri G, Puntoni M, Bottiglieri L, Varricchio C, et al. The effect of metformin on apoptosis in a breast cancer presurgical trial. Br J Cancer. 2013;109:2792–7. http://www.ncbi.nlm.nih.gov/pubmed/24157825.

28.

DeCensi A, Puntoni M, Gandini S, Guerrieri-Gonzaga A, Johansson HA, Cazzaniga M, et al. Differential effects of metformin on breast cancer proliferation according to markers of insulin resistance and tumor subtype in a randomized presurgical trial. Breast Cancer Res Treat. 2014;148:81–90. http://www.ncbi.nlm.nih.gov/pubmed/25253174.

29.

Ehab M, Elbaz M. Profile of palbociclib in the treatment of metastatic breast cancer. Breast Cancer. 2016;8:83–91. http://www.ncbi.nlm.nih.gov/pubmed/27274308.

30.

Vora SR, Juric D, Kim N, Mino-Kenudson M, Huynh T, Costa C, et al. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors. Cancer Cell. 2014;26:136–49. http://www.ncbi.nlm.nih.gov/pubmed/25002028.

31.

Stendahl M, Kronblad Å, Rydén L, Emdin S, Bengtsson NO, Landberg G. Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients. Br J Cancer. 2004;90:1942–8. http://www.ncbi.nlm.nih.gov/pubmed/15138475.

32.

Lehn S, Fernö M, Jirström K, Rydén L, Landberg G. A non-functional retinoblastoma tumor suppressor (RB) pathway in premenopausal breast cancer is associated with resistance to tamoxifen. Cell Cycle. 2011;10:956–62. http://www.ncbi.nlm.nih.gov/pubmed/21358261.

33.

Bosco EE, Wang Y, Xu H, Zilfou JT, Knudsen KE, Aronow BJ, et al. The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J Clin Invest. 2007;117:218–28. http://www.ncbi.nlm.nih.gov/pubmed/17160137.

34.

DeMichele A, Clark AS, Heitjan D, Randolph S, Gallagher M, Lal P, et al. Phase I study of PD 0332991, cyclin-D kinase (CDK) 4/6 inhibitor in combination with letrozole for first-line treatment of patients with ER-positive, HER2-negative breast cancer. 2010 ASCO Annual Meeting, Abstracts, Meeting Library. J Clin Oncol. 31 (suppl; abstr 519). 2013. http://meetinglibrary.asco.org/content/50680-74.

35.

Slamon DJ, Hurvitz SA, Applebaum S, Glaspy JA, Allison MK, DiCarlo BA, et al. A phase II trial of an oral CDK 4/6 inhibitor, PD0332991, in advanced breast cancer. 2013 ASCO Annual Meeting, Abstracts, Meeting Library. J Clin Oncol 2815 s, 2010 (suppl; abstr 3060). 2010. http://meetinglibrary.asco.org/content/113257-132.

36.

Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16:25–35. http://linkinghub.elsevier.com/retrieve/pii/S1470204514711593.

37.

Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, et al. Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med. 2015;373:209–19. http://www.ncbi.nlm.nih.gov/pubmed/26030518.

38.

Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375:1738–48. http://www.nejm.org/doi/10.1056/NEJMoa1609709.

39.

Munster PN, Hamilton EP, Franklin C, Bhansali S, Wan K, Hewes B, et al. Phase lb study of LEE011 and BYL719 in combination with letrozole in estrogen receptor-positive, HER2-negative breast cancer (ER+ , HER2− BC). 2014 ASCO Annual Meeting, Abstracts, Meeting Library. J Clin Oncol. 325 s, 2014 (suppl; abstr 533). 2014. http://meetinglibrary.asco.org/content/127461-144.

40.

Dickler MN, Tolaney SM, Rugo HS, Cortes J, Diéras V, Patt DA, et al. MONARCH1: Results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease.2016 ASCO Annual Meeting, Abstracts, Meeting Library. 2016 ASCO Annu. Meet. 2016. http://meetinglibrary.asco.org/content/164546-176.

41.

Tolaney SM, Rosen LS, Beeram M, Goldman JW, Gandhi AW, Papadopoulos KP, et al. Clinical activity of abemaciclib, an oral cell cycle inhibitor, in metastatic breast cancer. Cancer Res. 2015;75:P5-19-13. doi: 10.1158/1538-7445.SABCS14-P5-19-13CrossRef

42.

Robinson DR, Wu Y-M, Vats P, Su F, Lonigro RJ, Cao X, et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013;45:1446–51. http://www.ncbi.nlm.nih.gov/pubmed/24185510.

43.

Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45:1439–45. http://www.ncbi.nlm.nih.gov/pubmed/24185512.

44.

Weis KE, Ekena K, Thomas JA, Lazennec G, Katzenellenbogen BS. Constitutively active human estrogen receptors containing amino acid substitutions for tyrosine 537 in the receptor protein. Mol Endocrinol. 1996;10:1388–98. http://www.ncbi.nlm.nih.gov/pubmed/8923465.

45.

Zhang QX, Borg A, Wolf DM, Oesterreich S, Fuqua SA. An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res. 1997;57:1244–9. http://www.ncbi.nlm.nih.gov/pubmed/9102207.

46.

Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, et al. Emergence of constitutively active estrogen receptor- mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014;20:1757–67. http://www.ncbi.nlm.nih.gov/pubmed/24398047.

47.

Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A, Dvir A, Soussan-Gutman L, Jeselsohn R, et al. D538G mutation in estrogen receptor-: A novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res. 2013;73:6856–64. http://www.ncbi.nlm.nih.gov/pubmed/24217577.

48.

Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, Inao T, Sueta A, Fujiwara S, et al. Droplet digital polymerase chain reaction assay for screening of ESR1 mutations in 325 breast cancer specimens. Transl Res. 2015;166:540–553.e2. http://www.ncbi.nlm.nih.gov/pubmed/26434753.

49.

Wang P, Bahreini A, Gyanchandani R, Lucas PC, Hartmaier RJ, Watters RJ, et al. Sensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions, and cell-free DNA of breast cancer patients. Clin Cancer Res. 2016;22:1130–7. http://clincancerres.aacrjournals.org/cgi/doi/10.1158/1078-0432.CCR-15-1534.

50.

Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014;4:650–61. http://www.ncbi.nlm.nih.gov/pubmed/24801577.

51.

Chandarlapaty S, Chen D, He W, Sung P, Samoila A, You D, et al. Prevalence of ESR1 Mutations in cell-free DNA and outcomes in metastatic breast cancer. JAMA Oncol. 2016;2:1310. http://www.ncbi.nlm.nih.gov/pubmed/27532364.

52.

Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im S-A, Masuda N, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phas. Lancet Oncol. 2016;17:425–39. http://www.ncbi.nlm.nih.gov/pubmed/28153873.

53.

Fribbens C, OLeary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, et al. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2016;34:2961–8. http://www.ncbi.nlm.nih.gov/pubmed/27269946.

54.

Mayer I, Bardia A, Dickler M, Manning H, Mahmood U, Ulaner G, et al. Abstract OT3-2-07: Phase I study of ARN-810, a novel selective estrogen receptor degrader, in post-menopausal women with locally advanced or metastatic estrogen receptor positive breast cancer. Cancer Res. 2014;73:OT3-2-07-OT3-2-07. http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.SABCS13-OT3-2-07.

55.

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82. http://www.ncbi.nlm.nih.gov/pubmed/3798106.

56.

Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12. http://www.ncbi.nlm.nih.gov/pubmed/2470152.

57.

Yan M, Parker BA, Schwab R, Kurzrock R. HER2 aberrations in cancer: Implications for therapy. Cancer Treat Rev. 2014;40:770–80. http://www.ncbi.nlm.nih.gov/pubmed/24656976.

58.

Zell JA, Tsang WY, Taylor TH, Mehta RS, Anton-Culver H. Prognostic impact of human epidermal growth factor-like receptor 2 and hormone receptor status in inflammatory breast cancer (IBC): analysis of 2,014 IBC patient cases from the California Cancer Registry. Breast Cancer Res. 2009;11:R9. http://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr2225.

59.

Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92. http://www.ncbi.nlm.nih.gov/pubmed/11248153.

60.

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72. http://www.ncbi.nlm.nih.gov/pubmed/16236737.

61.

Witzel I, Müller V, Abenhardt W, Kaufmann M, Schoenegg W, Schneeweis A, et al. Long-term tumor remission under trastuzumab treatment for HER2 positive metastatic breast cancer—results from the HER-OS patient registry. BMC Cancer. 2014;14:806. http://www.ncbi.nlm.nih.gov/pubmed/25371387.

62.

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007;369:29–36. http://www.ncbi.nlm.nih.gov/pubmed/17208639.

63.

Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84. http://www.ncbi.nlm.nih.gov/pubmed/16236738.

64.

Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res. 2009;15:7479–91. http://www.ncbi.nlm.nih.gov/pubmed/20008848.

65.

Serra V, Scaltriti M, Prudkin L, Eichhorn PJA, Ibrahim YH, Chandarlapaty S, et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene. 2011;30:2547–57. http://www.ncbi.nlm.nih.gov/pubmed/21278786.

66.

Miller TW, Forbes JT, Shah C, Wyatt SK, Manning HC, Olivares MG, et al. Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells. Clin Cancer Res. 2009;15:7266–76. http://www.ncbi.nlm.nih.gov/pubmed/19934303.

67.

Wang Q, Liu P, Spangle JM, Von T, Roberts TM, Lin NU, et al. PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+ , PTEN-deficient breast cancers. Oncogene. 2016;35:3607–12. http://www.nature.com/doifinder/10.1038/onc.2015.406.

68.

Nagata Y, Lan K-H, Zhou X, Tan M, Esteva FJ, Sahin AA, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6:117–27. http://www.ncbi.nlm.nih.gov/pubmed/15324695.

69.

Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, et al. A functional genetic approach identifies the PI3K Pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12:395–402. http://www.ncbi.nlm.nih.gov/pubmed/17936563.

70.

Keck S, Glencer AC, Rugo HS. Everolimus and its role in hormone-resistant and trastuzumab-resistant metastatic breast cancer. Future Oncol. 2012;8:1383–96. http://www.ncbi.nlm.nih.gov/pubmed/23148612.

71.

Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. JNCI J Natl Cancer Inst. 2007;99:628–38. http://www.ncbi.nlm.nih.gov/pubmed/17440164.

72.

Yu Q, Sicinska E, Geng Y, Ahnström M, Zagozdzon A, Kong Y, et al. Requirement for CDK4 kinase function in breast cancer. Cancer Cell. 2006;9:23–32. http://www.ncbi.nlm.nih.gov/pubmed/16413469.

73.

Landis MW, Pawlyk BS, Li T, Sicinski P, Hinds PW. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell. 2006;9:13–22. http://linkinghub.elsevier.com/retrieve/pii/S153561080500396X.

74.

Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, et al. Overcoming therapeutic resistance in HER2-positive breast cancers with CDK4/6 Inhibitors. Cancer Cell. 2016;29:255–69. http://linkinghub.elsevier.com/retrieve/pii/S153561081630040X.

75.

Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, et al. Phase II Trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010;28:1138–44. http://www.ncbi.nlm.nih.gov/pubmed/20124182.

76.

Portera CC, Walshe JM, Rosing DR, Denduluri N, Berman AW, Vatas U, et al. Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with trastuzumab-insensitive human epidermal growth factor receptor 2-positive metastatic breast cancer. Clin Cancer Res. 2008;14:2710–6. http://www.ncbi.nlm.nih.gov/pubmed/18451236.

77.

Nahta R, Hung M-C, Esteva FJ. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res. 2004;64:2343–6. http://www.ncbi.nlm.nih.gov/pubmed/15059883.

78.

Zhang X, Munster PN. New protein kinase inhibitors in breast cancer: afatinib and neratinib. Expert Opin Pharmacother. 2014;15:1277–88. http://www.tandfonline.com/doi/full/10.1517/14656566.2014.913570.

79.

Chung A, Cui X, Audeh W, Giuliano A. Current status of anti-human epidermal growth factor receptor 2 therapies: predicting and overcoming herceptin resistance. Clin Breast Cancer. 2013;13:223–32. http://linkinghub.elsevier.com/retrieve/pii/S1526820913001006.

80.

Saini KS, Azim HA, Metzger-Filho O, Loi S, Sotiriou C, de Azambuja E, et al. Beyond trastuzumab: new treatment options for HER2-positive breast cancer. The Breast. 2011;20:S20–7. http://www.ncbi.nlm.nih.gov/pubmed/22015288.

81.

Scaltriti M, Chandarlapaty S, Prudkin L, Aura C, Jimenez J, Angelini PD, et al. Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptor. Clin Cancer Res. 2010;16:2688–95. http://clincancerres.aacrjournals.org/cgi/doi/10.1158/1078-0432.CCR-09-3407.

82.

Dave B, Migliaccio I, Gutierrez MC, Wu M-F, Chamness GC, Wong H, et al. Loss of phosphatase and tensin homolog or phosphoinositol-3 kinase activation and response to trastuzumab or lapatinib in human epidermal growth factor receptor 2-overexpressing locally advanced breast cancers. J Clin Oncol. 2011;29:166–73. http://www.ncbi.nlm.nih.gov/pubmed/21135276.

83.

Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, Aura C, De Azambuja E. First results of the NeoALTTO trial (BIG 01-06/EGF 106903): a phase III, randomized, open label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. Presented at the 33rd annual San Antonio breast cancer symposium; 2010 (abstract S3-3)

84.

Gianni L, Pienkowski T, Im Y-H, Roman L, Tseng L-M, Liu M-C, et al. Neoadjuvant pertuzumab (P) and trastuzumab (H): antitumor and safety analysis of a randomized phase II study (’NeoSphere’). Cancer Res 2010;70(24 Suppl):Abstract nr S3-2

85.

Baselga J, Cortés J, Kim S-B, Im S-A, Hegg R, Im Y-H, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl. J Med. 2012;366:109–19. http://www.ncbi.nlm.nih.gov/pubmed/22149875.

86.

Amiri-Kordestani L, Wedam S, Zhang L, Tang S, Tilley A, Ibrahim A, et al. First FDA approval of neoadjuvant therapy for breast cancer: pertuzumab for the treatment of patients with HER2-positive breast cancer. Clin Cancer Res. 2014;20:5359–64. http://www.ncbi.nlm.nih.gov/pubmed/25204553.

87.

Saini KS, Azim HA, Metzger-Filho O, Loi S, Sotiriou C, de Azambuja E, et al. Beyond trastuzumab: new treatment options for HER2-positive breast cancer. Breast. 2011;20 Suppl 3:S20-7. http://linkinghub.elsevier.com/retrieve/pii/S0960977611702892.

88.

Saura C, Garcia-Saenz JA, Xu B, Harb W, Moroose R, Pluard T, et al. Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2014;32:3626–33. http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2014.56.3809.

89.

Chow LW-C, Xu B, Gupta S, Freyman A, Zhao Y, Abbas R, et al. Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. Br J Cancer. 2013;108:1985–93. http://www.ncbi.nlm.nih.gov/pubmed/23632474.

90.

Martin M, Bonneterre J, Geyer CE, Ito Y, Ro J, Lang I, et al. A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. Eur J Cancer. 2013;49:3763–72. http://linkinghub.elsevier.com/retrieve/pii/S0959804913007181.

91.

Cortés J, Dieras V, Ro J, Barriere J, Bachelot T, Hurvitz S, et al. Afatinib alone or afatinib plus vinorelbine versus investigator’s choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 tr. Lancet Oncol. 2015;16:1700–10. http://dx.doi.org/10.1016/j.ccr.2012.02.022.

92.

Weil RJ, Palmieri DC, Bronder JL, Stark AM, Steeg PS. Breast cancer metastasis to the central nervous system. Am J Pathol. 2005;167:913–20. http://www.ncbi.nlm.nih.gov/pubmed/16192626.

93.

Montagna E, Cancello G, D’Agostino D, Lauria R, Forestieri V, Esposito A, et al. Central nervous system metastases in a cohort of metastatic breast cancer patients treated with trastuzumab. Cancer Chemother Pharmacol. 2009;63:275–80. http://www.ncbi.nlm.nih.gov/pubmed/18379783.

94.

Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J Clin Oncol. 2010;28:2698–704. http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2009.26.2071.

95.

Isakoff SJ, Baselga J. Trastuzumab-DM1: building a chemotherapy-free road in the treatment of human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2011;29:351–4. http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2010.31.6679.

96.

Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783–91. http://www.ncbi.nlm.nih.gov/pubmed/23020162.

97.

Miller K, Cortes J, Hurvitz SA, Krop IE, Tripathy D, Verma S, et al. HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer. BMC Cancer. 2016;16:352. http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2385-z.

98.

André F, O’Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15:580–91. http://linkinghub.elsevier.com/retrieve/pii/S147020451470138X.

99.

Coley WB. The Treatment of Inoperable Sarcoma by Bacterial Toxins (the Mixed Toxins of the Streptococcus erysipelas and the Bacillus prodigiosus). Proc R Soc Med. 1910;3:1–48. http://www.ncbi.nlm.nih.gov/pubmed/19974799.

100.

Raedler LA. Keytruda (Pembrolizumab): First PD-1 inhibitor approved for previously treated unresectable or metastatic melanoma. Am Health Drug Benefits. 2015;8:96–100. http://www.ncbi.nlm.nih.gov/pubmed/26629272.

101.

Sul J, Blumenthal GM, Jiang X, He K, Keegan P, Pazdur R. FDA Approval summary: pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1. Oncologist. 2016;21:643–50. http://www.ncbi.nlm.nih.gov/pubmed/27026676.

102.

Ruffell B, Au A, Rugo HS, Esserman LJ, Hwang ES, Coussens LM. Leukocyte composition of human breast cancer. Proc Natl Acad Sci. 2012;109:2796–801. http://www.ncbi.nlm.nih.gov/pubmed/21825174.

103.

Coventry BJ, Weightman MJ, Bradley J, Skinner JM. Immune profiling in human breast cancer using high-sensitivity detection and analysis techniques. JRSM Open. 2015;6:205427041560390. http://www.ncbi.nlm.nih.gov/pubmed/26464809.

104.

Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, et al. Prognostic and predictive value of tumor-infiltrating 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;31:860–7. http://www.ncbi.nlm.nih.gov/pubmed/23341518.

105.

Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027–34. http://www.ncbi.nlm.nih.gov/pubmed/11015443.

106.

Ali HR, Glont S-E, Blows FM, Provenzano E, Dawson S-J, Liu B, et al. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol. 2015;26:1488–93. http://www.ncbi.nlm.nih.gov/pubmed/25897014.

107.

Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, et al. PD-L1 Expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res. 2015;3:326–32. http://www.ncbi.nlm.nih.gov/pubmed/25527356.

108.

Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali HR, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget.2015;6:5449–64. http://www.ncbi.nlm.nih.gov/pubmed/25669979.

109.

Mittendorf EA, Philips A V., Meric-Bernstam F, Qiao N, Wu Y, Harrington S, et al. PD-L1 Expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2:361–70. http://www.ncbi.nlm.nih.gov/pubmed/24764583.

110.

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. [Internet]. 2016 [cited 2017 Feb 13];13:674–90. http://www.ncbi.nlm.nih.gov/pubmed/27184417.

111.

Issa-Nummer Y, Darb-Esfahani S, Loibl S, Kunz G, Nekljudova V, Schrader I, et al. Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer—a substudy of the neoadjuvant GeparQuinto trial. PLoS One. 2013;8:e79775. http://www.ncbi.nlm.nih.gov/pubmed/24312450.

112.

García-Teijido P, Cabal ML, Fernández IP, Pérez YF. Tumor-Infiltrating lymphocytes in triple negative breast cancer: the future of immune targeting. Clin Med Insights Oncol. Libertas Academica; 2016;10:31–9. http://www.ncbi.nlm.nih.gov/pubmed/27081325.

113.

West NR, Milne K, Truong PT, Macpherson N, Nelson BH, Watson PH. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res. 2011;13:R126. http://www.ncbi.nlm.nih.gov/pubmed/22151962.

114.

Desmedt C, Di Leo A, de Azambuja E, Larsimont D, Haibe-Kains B, Selleslags J, et al. Multifactorial approach to predicting resistance to anthracyclines. J Clin Oncol. 2011;29:1578–86. http://www.ncbi.nlm.nih.gov/pubmed/21422418.

115.

Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8:59–73. http://www.ncbi.nlm.nih.gov/pubmed/18097448.

116.

Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discov. 2012;11:215–33. http://www.ncbi.nlm.nih.gov/pubmed/22301798.

117.

Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, et al. Prognostic and predictive value of tumor-infiltrating 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;31:860–7. http://www.ncbi.nlm.nih.gov/pubmed/23341518.

118.

Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, 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;32:2959–66. http://www.ncbi.nlm.nih.gov/pubmed/25071121.

119.

Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014;25:1544–50. http://www.ncbi.nlm.nih.gov/pubmed/24608200.

120.

Nagalla S, Chou JW, Willingham MC, Ruiz J, Vaughn JP, Dubey P, et al. Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis. Genome Biol. 2013;14:R34. http://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-4-r34.

121.

Rody A, Karn T, Liedtke C, Pusztai L, Ruckhaeberle E, Hanker L, et al. A clinically relevant gene signature in triple negative and basal-like breast cancer. Breast Cancer Res. 2011;13:R97. http://www.ncbi.nlm.nih.gov/pubmed/21978456.

122.

Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, et al. A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat. 2011;126:407–20. http://www.ncbi.nlm.nih.gov/pubmed/20490655.

123.

Staaf J, Ringner M, Vallon-Christersson J, Jonsson G, Bendahl PO, Holm K, et al. Identification of Subtypes in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Reveals a Gene Signature Prognostic of Outcome. J Clin Oncol. 2010;28:1813–20. http://www.ncbi.nlm.nih.gov/pubmed/20231686.

124.

Rody A, Holtrich U, Pusztai L, Liedtke C, Gaetje R, Ruckhaeberle E, et al. T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers. Breast Cancer Res. 2009;11:R15. http://www.ncbi.nlm.nih.gov/pubmed/19272155.

125.

Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C. An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol. 2007;8:R157. http://www.ncbi.nlm.nih.gov/pubmed/17683518.

126.

Callari M, Cappelletti V, D’Aiuto F, Musella V, Lembo A, Petel F, et al. Subtype-specific metagene-based prediction of outcome after neoadjuvant and adjuvant treatment in breast cancer. Clin. Cancer Res. 2016;22:337–45. http://www.ncbi.nlm.nih.gov/pubmed/26423797.

127.

Gu-Trantien C, Loi S, Garaud S, Equeter C, Libin M, de Wind A, et al. CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. J Clin Invest. American Society for Clinical Investigation; 2013;123:2873–92. http://www.ncbi.nlm.nih.gov/pubmed/23778140.

128.

Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G, et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res. 2008;14:5158–65. http://www.ncbi.nlm.nih.gov/pubmed/18698033.

129.

Bianchini G, Qi Y, Alvarez RH, Iwamoto T, Coutant C, Ibrahim NK, et al. Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers. J Clin Oncol. 2010;28:4316–23. http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2009.27.2419.

130.

Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, et al. The Humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res. 2008;68:5405–13. http://cancerres.aacrjournals.org/cgi/doi/10.1158/0008-5472.CAN-07-5206.

131.

Pusztai L, Karn T, Safonov A, Abu-Khalaf MM, Bianchini G. New strategies in breast cancer: immunotherapy. Clin Cancer Res. 2016;22:2105–10. http://www.ncbi.nlm.nih.gov/pubmed/26867935.

132.

Nanda R, Chow LQM, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016;34:2460–7. http://www.ncbi.nlm.nih.gov/pubmed/27138582.

133.

Emens LA, Braiteh FS, Cassier P, et al. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer; Presented at San Antonio Breast Cancer Symposium; December 9–13, 2014; San Antonio, TXCrossRef

134.

Wang X, Teng F, Kong L, Yu J. PD-L1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther. Dove Press; 2016;9:5023–39. http://www.ncbi.nlm.nih.gov/pubmed/27574444.

135.

Grigg C, Rizvi NA. PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction? J Immunother Cancer. BioMed Central; 2016;4:48. http://www.ncbi.nlm.nih.gov/pubmed/27532023.

136.

Turner NC, Lord CJ, Iorns E, Brough R, Swift S, Elliott R, et al. A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor. EMBO J. European Molecular Biology Organization; 2008;27:1368–77. http://www.ncbi.nlm.nih.gov/pubmed/18388863.

137.

Ibrahim YH, García-García C, Serra V, He L, Torres-Lockhart K, Prat A, et al. PI3K Inhibition Impairs BRCA1/2 Expression and Sensitizes BRCA-Proficient Triple-Negative Breast Cancer to PARP Inhibition. Cancer Discov. 2012;2:1036–47. http://www.ncbi.nlm.nih.gov/pubmed/22915752.

138.

Tate CR, Rhodes L V, Segar HC, Driver JL, Pounder FN, Burow ME, et al. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res. 2012;14:R79. http://www.ncbi.nlm.nih.gov/pubmed/22613095.

139.

Schech A, Kazi A, Yu S, Shah P, Sabnis G. Histone Deacetylase Inhibitor Entinostat inhibits tumor-initiating cells in triple-negative breast cancer cells. Mol Cancer Ther. 2015;14:1848–57. http://www.ncbi.nlm.nih.gov/pubmed/26037781.

140.

Hoeflich KP, O’Brien C, Boyd Z, Cavet G, Guerrero S, Jung K, et al. In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin Cancer Res. 2009;15:4649–64. http://www.ncbi.nlm.nih.gov/pubmed/19567590.

141.

Caldas-Lopes E, Cerchietti L, Ahn JH, Clement CC, Robles AI, Rodina A, et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc Natl Acad Sci. 2009;106:8368–73. http://www.ncbi.nlm.nih.gov/pubmed/19416831.

142.

Zagouri F, Sergentanis TN, Chrysikos D, Papadimitriou CA, Dimopoulos M-A, Psaltopoulou T. Hsp90 inhibitors in breast cancer: a systematic review. The Breast. 2013;22:569–78. http://www.ncbi.nlm.nih.gov/pubmed/23870456.

143.

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J. Clin. Invest. American Society for Clinical Investigation; 2011;121:2750–67. http://www.ncbi.nlm.nih.gov/pubmed/21633166.

144.

Wesche J, Haglund K, Haugsten EM. Fibroblast growth factors and their receptors in cancer. Biochem J. 2011;437:199–213. http://www.ncbi.nlm.nih.gov/pubmed/21711248.

145.

Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10:116–29. http://www.ncbi.nlm.nih.gov/pubmed/20094046.

Title: Advances in systemic therapy for metastatic breast cancer: future perspectives
Authors: S. P. Corona
N. Sobhani
A. Ianza
G. Roviello
G. Mustacchi
M. Bortul
F. Zanconati
D. Generali
Publication date: 01-07-2017
Publisher: Springer US
Published in: Medical Oncology / Issue 7/2017
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-017-0975-5

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Advances in systemic therapy for metastatic breast cancer: future perspectives

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2017

Aberrant gene promoter methylation of E-cadherin, p16 INK4a , p14 ARF , and MGMT in Epstein–Barr virus-associated oral squamous cell carcinomas

Peribiliary liver metastases MR findings

Expanding the search for significant EGFR mutations in NSCLC outside of the tyrosine kinase domain with next-generation sequencing

Extended adjuvant endocrine therapy in early breast cancer: a meta-analysis of published randomized trials

Minimally invasive pancreatic cancer surgery: What is the current evidence?

Epithelial-to-mesenchymal transition in tumor progression

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page