Photo of Steven J. Isakoff,   M.D. Ph.D.

Steven J. Isakoff, M.D. Ph.D.

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-4920
Fax: (617) 643-0589

Steven J. Isakoff, M.D. Ph.D.

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Instructor, Medicine, Harvard Medical School
  • Assistant in Medicine, MGH Cancer Center, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Co-Chair, Breast Cancer Program, Clinical Research Committee

Research Abstract

My research interest focuses on the basic biology, pathology, and treatment of Breast cancer. My laboratory work focuses on the role of PI3K in breast cancer and the role of activating mutation in PI3K in breast cancer pathogenesis. I am also interested in translational research projects in breast cancer evaluating the clinical effect of alterations in the PI3K pathway. This interest also involves understanding the role of alterations in PI3K signaling on resistance to anti-tumour therapies. My clinical interest in the development of novel therapies for treating breast cancer through clinical trials.

Publications

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  • 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. PubMed
  • Mayer IA, Abramson VG, Isakoff SJ, Forero A, Balko JM, Kuba MG, Sanders ME, Yap JT, Van den Abbeele AD, Li Y, Cantley LC, Winer E, Arteaga CL. Stand up to cancer phase ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 2014; 32:1202-9. PubMed
  • Gradishar WJ, Anderson BO, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Hayes DF, Hudis CA, Isakoff SJ, Ljung BM, Marcom PK, Mayer IA, McCormick B, Miller RS, Pegram M, Pierce LJ, Reed EC, Salerno KE, Schwartzberg LS, Smith ML, Soliman H, Somlo G, Ward JH, Wolff AC, Zellars R, Shead DA, Kumar R. Breast cancer version 3.2014. J Natl Compr Canc Netw 2014; 12:542-90. PubMed
  • Fan L, Liedke PE, Isakoff SJ, St Louis J, Ryan PD, Goss PE. Intermittent letrozole therapy for metastatic breast cancer: case reports and literature review. Clin Breast Cancer 2014; 14:e41-5. PubMed
  • Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, Stearns V, Doane AS, Danso M, Moynahan ME, Momen LF, Gonzalez JM, Akhtar A, Giri DD, Patil S, Feigin KN, Hudis CA, Traina TA, . Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res 2013; 19:5505-12. PubMed
  • Kansal KJ, Dominici LS, Tolaney SM, Isakoff SJ, Smith BL, Jiang W, Brock JE, Winer EP, Krop IE, Golshan M. Neoadjuvant bevacizumab: surgical complications of mastectomy with and without reconstruction. Breast Cancer Res Treat 2013; 141:255-9. PubMed
  • Specht MC, Miller CL, Skolny MN, Jammallo LS, O'Toole J, Horick N, Isakoff SJ, Smith BL, Taghian AG. Residual lymph node disease after neoadjuvant chemotherapy predicts an increased risk of lymphedema in node-positive breast cancer patients. Ann Surg Oncol 2013; 20:2835-41. PubMed
  • Theriault RL, Carlson RW, Allred C, Anderson BO, Burstein HJ, Edge SB, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Isakoff SJ, Ljung BM, Mankoff DA, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Schwartzberg LS, Smith ML, Soliman H, Somlo G, Ward JH, Wolff AC, Zellars R, Shead DA, Kumar R, . Breast cancer, version 3.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2013; 11:753-60; quiz 761. PubMed
  • Macdonald SM, Patel SA, Hickey S, Specht M, Isakoff SJ, Gadd M, Smith BL, Yeap BY, Adams J, Delaney TF, Kooy H, Lu HM, Taghian AG. Proton Therapy for Breast Cancer After Mastectomy: Early Outcomes of a Prospective Clinical Trial. Int J Radiat Oncol Biol Phys 2013. PubMed
  • Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 2013; 339:580-4. PubMed
  • Carp SA, Sajjadi AY, Wanyo CM, Fang Q, Specht MC, Schapira L, Moy B, Bardia A, Boas DA, Isakoff SJ. Hemodynamic signature of breast cancer under fractional mammographic compression using a dynamic diffuse optical tomography system. Biomed Opt Express 2014; 4:2911-24. PubMed
  • Mayer EL, Isakoff SJ, Klement G, Downing SR, Chen WY, Hannagan K, Gelman R, Winer EP, Burstein HJ. Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative platelet proteomics. Breast Cancer Res Treat 2012; 136:169-78. PubMed
  • 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. PubMed
  • Isakoff SJ. PARP Inhibition Outside of BRCA Mutation Carriers. Clin Adv Hematol Oncol 2011; 8:757-8. PubMed
  • Dias-Santagata D, Akhavanfard S, David SS, Vernovsky K, Kuhlmann G, Boisvert SL, Stubbs H, McDermott U, Settleman J, Kwak EL, Clark JW, Isakoff SJ, Sequist LV, Engelman JA, Lynch TJ, Haber DA, Louis DN, Ellisen LW, Borger DR, Iafrate AJ. Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine. EMBO Mol Med 2010; 2:146-58. PubMed
  • Mina L,Krop I,Zon RT,Isakoff SJ,Schneider CJ,Yu M,Johnson C,Vaughn LG,Wang Y,Hristova-Kazmierski M,Shonukan OO,Sledge GW,Miller KD. A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen. Invest New Drugs 2009. PubMed
  • Naffar-Abu-Amara S, Shay T, Galun M, Cohen N, Isakoff SJ, Kam Z, Geiger B. Identification of novel pro-migratory, cancer-associated genes using quantitative, microscopy-based screening. PLoS ONE 2008; 3:e1457. PubMed
  • Haile RW, Thomas DC, McGuire V, Felberg A, John EM, Milne RL, Hopper JL, Jenkins MA, Levine AJ, Daly MM, Buys SS, Senie RT, Andrulis IL, Knight JA, Godwin AK, Southey M, McCredie MR, Giles GG, Andrews L, Tucker K, Miron A, Apicella C, Tesoriero A, Bane A, Pike MC, Whittemore AS. BRCA1 and BRCA2 Mutation Carriers, Oral Contraceptive Use, and Breast Cancer Before Age 50. Cancer Epidemiol Biomarkers Prev 2006; 15:1863-70. PubMed
  • Golshan M, Miron A, Nixon AJ, Garber JE, Cash EP, Iglehart JD, Harris JR, Wong JS. The prevalence of germline BRCA1 and BRCA2 mutations in young women with breast cancer undergoing breast-conservation therapy. Am J Surg 2006; 192:58-62. PubMed
  • Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S. X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 2006; 9:121-32. PubMed
  • Lee JS, John EM, McGuire V, Felberg A, Ostrow KL, DiCioccio RA, Li FP, Miron A, West DW, Whittemore AS. Breast and ovarian cancer in relatives of cancer patients, with and without BRCA mutations. Cancer Epidemiol Biomarkers Prev 2006; 15:359-63. PubMed
  • Spurdle AB, Antoniou AC, Kelemen L, Holland H, Peock S, Cook MR, Smith PL, Greene MH, Simard J, Plourde M, Southey MC, Godwin AK, Beck J, Miron A, Daly MB, Santella RM, Hopper JL, John EM, Andrulis IL, Durocher F, Struewing JP, Easton DF, Chenevix-Trench G. The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 2006; 15:76-9. PubMed
  • Zhang X, Lu X, Shi Q, Xu XQ, Leung HC, Harris LN, Iglehart JD, Miron A, Liu JS, Wong WH. Recursive SVM feature selection and sample classification for mass-spectrometry and microarray data. BMC Bioinformatics 2006; 7:197. PubMed
  • Matros E, Wang ZC, Lodeiro G, Miron A, Iglehart JD, Richardson AL. BRCA1 promoter methylation in sporadic breast tumors: relationship to gene expression profiles. Breast Cancer Res Treat 2005; 91:179-86. PubMed
  • Ganesan S, Richardson AL, Wang ZC, Iglehart JD, Miron A, Feunteun J, Silver D, Livingston DM. Abnormalities of the Inactive X Chromosome Are a Common Feature of BRCA1 Mutant and Sporadic Basal-like Breast Cancer. Cold Spring Harb Symp Quant Biol 2006; 70:93-7. PubMed
  • Miron A, Schildkraut JM, Rimer BK, Winer EP, Sugg Skinner C, Futreal PA, Culler D, Calingaert B, Clark S, Kelly Marcom P, Iglehart JD. Testing for hereditary breast and ovarian cancer in the southeastern United States. Ann Surg 2000; 231:624-34. PubMed
  • Leone G, Nuckolls F, Ishida S, Adams M, Sears R, Jakoi L, Miron A, Nevins JR. Identification of a novel E2F3 product suggests a mechanism for determining specificity of repression by Rb proteins. Mol Cell Biol 2000; 20:3626-32. PubMed
  • Isakoff SJ. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J 2010; 16:53-61. PubMed
  • Glick JL, Meigs TE, Miron A, Casey PJ. RGSZ1, a Gz-selective regulator of G protein signaling whose action is sensitive to the phosphorylation state of Gzalpha. J Biol Chem 1998; 273:26008-13. PubMed
  • Berchuck A, Heron KA, Carney ME, Lancaster JM, Fraser EG, Vinson VL, Deffenbaugh AM, Miron A, Marks JR, Futreal PA, Frank TS. Frequency of germline and somatic BRCA1 mutations in ovarian cancer. Clin Cancer Res 1998; 4:2433-7. PubMed
  • Iglehart JD, Miron A, Rimer BK, Winer EP, Berry D, Shildkraut MJ. Overestimation of hereditary breast cancer risk. Ann Surg 1998; 228:375-84. PubMed
  • DeGregori J, Leone G, Miron A, Jakoi L, Nevins JR. Distinct roles for E2F proteins in cell growth control and apoptosis. Proc Natl Acad Sci U S A 1997; 94:7245-50. PubMed
  • DeGregori J, Leone G, Ohtani K, Miron A, Nevins JR. E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity. Genes Dev 1995; 9:2873-87. PubMed
  • Miron A, Patel I, Bastia D. Multiple pathways of copy control of gamma replicon of R6K: mechanisms both dependent on and independent of cooperativity of interaction of tau protein with DNA affect the copy number. Proc Natl Acad Sci U S A 1994; 91:6438-42. PubMed
  • Natarajan S, Kaul S, Miron A, Bastia D. A 27 kd protein of E. coli promotes antitermination of replication in vitro at a sequence-specific replication terminus. Cell 1993; 72:113-20. PubMed
  • Miron A, Mukherjee S, Bastia D. Activation of distant replication origins in vivo by DNA looping as revealed by a novel mutant form of an initiator protein defective in cooperativity at a distance. EMBO J 1992; 11:1205-16. PubMed
  • MacAllister TW, Kelley WL, Miron A, Stenzel TT, Bastia D. Replication of plasmid R6K origin gamma in vitro. Dependence on dual initiator proteins and inhibition by transcription. J Biol Chem 1991; 266:16056-62. PubMed
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