Cores

Administration, Advocacy, Planning and Communication Core

Core Director: Eric P. Winer, MD, (DFCI)
Core Co-Directors: Joan Brugge, PhD (HMS) & Kornelia Polyak, MD, PhD, (DFCI)
Core Co-Investigator:
 Shom Goel, MBBS, PhD
Core Aims: The AAPC Core has focused efforts on

  1. The administrative and fiscal management needs of the DF/HCC Breast SPORE
  2. Promoting scientific leadership and planning to promote collaboration and scientific advancement
  3. Fostering a strong patient advocate community able to boost the visibility of patient perspective in research
  4. Ensuring communication is shared throughout the institutions that make up the DF/HCC Breast Program in an effective and timely manner.

Biostatistics and Computational Biology Core

Core Co-Directors: William T. Barry, PhD (DFCI), Meredith M. Regan, ScD
Core Aims:

  1. Provide biostatistical and computational biology expertise for the planning and design, conduct, analysis, and reporting of laboratory, genomic, animal, translational, clinical (including associated correlative studies), and epidemiological studies for SPORE Projects, Developmental Research and Career Development projects, and other SPORE Cores.
  2. Provide consultation on all issues of data management and integrity, including data collection, storage, transfer and quality assurance, on statistical and computational biology software and programs, and on coordination of laboratory results with parameters and outcomes from clinical studies or clinical/translational research databases.
  3. Provide short-term biostatistics and computational biology consulting to the entire group of SPORE researchers. 

Tissue and Pathology Core

Core Director: Deborah Dillon, MD
Core Aims:

  1. To provide a tissue and blood repository for use by SPORE investigators
  2. To collect, store, process, and analyze tissue and blood from participants on SPORE clinical trials with attention to informed consent, patient confidentiality, specimen handling, and specimen use
  3. To facilitate a culture of patient derived tissue-based translational research for the SPORE and Harvard investigators through the provision of accessible pathology and technical services, integrated with clinical information

Core Publications

Core B: Biostatistics and Computational Biology

Janiszewska M, Liu L, Almendro V, Kuang Y, Paweletz C, Sakr RA, Weigelt B, Hanker AB, Chandarlapaty S, King TA, Reis-Filho JS, Arteaga CL, Park SY, Michor F, Polyak K. In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer. Nat Genet. 2015;47(10):1212-9. PMCID: PMC4589505.

Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, Janiszewska M, Huh SJ, Liang Y, Ryan J, Doherty E, Mohammed H, Guo H, Stover DG, Ekram MB, Brown J, D'Santos C, Krop IE, Dillon D, McKeown M, Ott C, Qi J, Ni M, Rao PK, Duarte M, Wu SY, Chiang CM, Anders L, Young RA, Winer E, Letai A, Barry WT, Carroll JS, Long H, Brown M, Liu XS, Meyer CA, Bradner JE, Polyak K. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature. 2016;529(7586):413-7. PMCID: PMC4854653.

Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nat Med. 2016;22(7):723-6. PMCID: PMC4938731. 

Matulonis UA, Wulf GM, Barry WT, Birrer M, Westin SN, Farooq S, Bell-McGuinn KM, Obermayer E, Whalen C, Spagnoletti T, Luo W, Liu H, Hok RC, Aghajanian C, Solit DB, Mills GB, Taylor BS, Won H, Berger MF, Palakurthi S, Liu J, Cantley LC, Winer E. Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer. Ann Oncol. 2017;28(3):512-8. PMID: 27993796.

Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Farooq S, Cadoo K, Whalen C, Luo W, Liu H, Aghajanian C, Solit DB, Mills GB, Taylor BS, Won H, Berger MF, Palakurthi S, Liu JF, Cantley LC, Kaufmann SH, Swisher EM, D'Andrea AD, Winer E, Wulf GM, Matulonis UA. Phase 1 study of the alpha-specific PI3 kinase inhibitor BYL719 and the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in recurrent ovarian and breast cancer: analysis of the dose escalation and ovarian cancer expansion cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACRS; Cancer Res. 2017;77(13 Suppl):Abstract nr CT008.

Metzger Filho O, Goel S, Barry WT, Hamilton EP, Tolaney SM, Yardley DA, Rees R, Demeo M, Mills C, Hafner M, Winer EP, Zhao J, Krop IE. A mouse-human phase I co-clinical trial of taselisib in combination with TDM1 in advanced HER2-positive breast cancer (MBC). J Clin Oncol. 2017;35(15 suppl):1030.

Del Alcazar CG, Huh SJ, Ekram M,  Trinh A, Liu LL, Beca F, Zi X, Kwak M, Bergholtz H, Su Y, Ding L, Russnes HG, Richardson AL, Babski K, Min Hui Kim E, McDonnell C, Wagner J, Rowberry R, Freeman GJ, Dillon D, Sorlie T, Coussens LM, Garber JE, Fan R, Bobolis K, Allred DC, Jeong J, Park SY, Michor F, Polyak K. Immune escape in breast cancer during in situ to invasive carcinoma transition. Cancer Discov. 2017 Jun 26 [Epub ahead of print]. doi: 10.1158/2159-8290.CD-17-0222 PMID: 28652380.

Core C: Biospecimen and Pathology Core

Wang Y, Lee YM, Baitsch L, Huang A, Xiang Y, Tong H, Lako A, Von T, Choi C, Lim E, Min J, Li L, Stegmeier F, Schlegel R, Eck MJ, Gray NS, Mitchison TJ, Zhao JJ. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife. 2014;3:e01763. PMCID: PMC4059381.

Lim E, Ni M, Cao S, Hazra A, Tamimi RM, Brown M. Importance of breast cancer subtype in the development of androgen receptor directed therapy. Curr Breast Cancer Rep. 2014;6(2):71-8. PMCID: PMC4026357.

Vora SR, Juric D, Kim N, Mino-Kenudson M, Huynh T, Costa C, Lockerman EL, Pollack SF, Liu M, Li X, Lehar J, Wiesmann M, Wartmann M, Chen Y, Cao ZA, Pinzon-Ortiz M, Kim S, Schlegel R, Huang A, Engelman JA. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors. Cancer Cell. 2014;26(1):136-49. PMCID: PMC4155598.

Costa C, Ebi H, Martini M, Beausoleil SA, Faber AC, Jakubik CT, Huang A, Wang Y, Nishtala M, Hall B, Rikova K, Zhao J, Hirsch E, Benes CH, Engelman JA. Measurement of PIP3 levels reveals an unexpected role for p110β in early adaptive responses to p110α-specific inhibitors in luminal breast cancer. Cancer Cell. 2015;27(1):97-108. PMCID: PMC4745884.

Zhang X, Eliassen AH, Tamimi RM, Hazra A, Beck AH, Brown M, Collins LC, Rosner B, Hankinson SE. Adult body size and physical activity in relation to risk of breast cancer according to tumor androgen receptor status. Cancer Epidemiol Biomarkers Prev. 2015;24(6):962-8. PMCID: PMC4452447.

Wang Y, Zhang T, Kwiatkowski N, Abraham BJ, Lee TI, Xie S, Yuzugullu H, Von T, Li H, Lin Z, Stover DG, Lim E, Wang ZC, Iglehart JD, Young RA, Gray NS, Zhao JJ. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell. 2015;163(1):174-86. PMCID: PMC4583659. 

Wang J, Zhang X, Beck AH, Collins LC, Chen WY, Tamimi RM, Hazra A, Brown M, Rosner B, Hankinson SE. Alcohol consumption and risk of breast cancer by tumor receptor expression. Horm Cancer. 2015;6(5-6):237-46. PMCID: PMC4631632.

Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, Janiszewska M, Huh SJ, Liang Y, Ryan J, Doherty E, Mohammed H, Guo H, Stover DG, Ekram MB, Brown J, D'Santos C, Krop IE, Dillon D, McKeown M, Ott C, Qi J, Ni M, Rao PK, Duarte M, Wu SY, Chiang CM, Anders L, Young RA, Winer E, Letai A, Barry WT, Carroll JS, Long H, Brown M, Liu XS, Meyer CA, Bradner JE, Polyak K. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature. 2016;529(7586):413-17. PMCID: PMC4854653.

Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, Tuck D, Harris LN, Wong KK, Liu XS, Sicinski P, Winer EP, Krop IE, Zhao JJ. Overcoming therapeutic resistance in HER2-positive breast cancers with CDK4/6 inhibitors. Cancer Cell. 2016;29(3):255–69. PMCID: PMC4794996. 

Huh SJ, Oh H, Peterson MA, Almendro V, Hu R, Bowden M, Lis RL, Cotter M, Loda M, Barry WT, Polyak K, Tamimi RM. The proliferative activity of mammary epithelial cells in normal tissue predicts breast cancer risk in premenopausal women. Cancer Res. 2016;76(7):1926-34. PMCID: PMC4873436.

Cheng H, Liu P, Ohlson C, Xu E, Symonds L, Isabella A, Muller WJ, Lin NU, Krop IE, Roberts TM, Winer EP, Arteaga CL, Zhao JJ. PIK3CA H1047R- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling. Oncogene. 2016;35(23):2961-70. PMCID: PMC4896860.

Wang Q, Liu P, Spangle JM, Von T, Roberts TM, Lin NU, Krop IE, Winer EP, Zhao JJ. PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers. Oncogene. 2016;35(27):3607-12. PMCID: PMC4846581.

Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nat Med. 2016;22(7):723-6. PMCID: PMC4938731. 

Wang Y, Begley M, Li Q, Huang HT, Lako A, Eck MJ, Gray NS, Mitchison TJ, Cantley LC, Zhao JJ. Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival. Proc Natl Acad Sci U S A. 2016;113(35):9810-5. PMCID: PMC5024598. 

Johnson SF, Cruz C, Greifenberg AK, Dust S, Stover DG, Chi D, Primack B, Cao S, Bernhardy AJ, Coulson R, Lazaro JB, Kochupurakkal B, Sun H, Unitt C, Moreau LA, Sarosiek KA, Scaltriti M, Juric D, Baselga J, Richardson AL, Rodig SJ, D'Andrea AD, Balmaña J, Johnson N, Geyer M, Serra V, Lim E, Shapiro GI. CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer. Cell Rep. 2016;17(9):2367-81. PMCID: PMC5176643. 

Matulonis UA, Wulf GM, Barry WT, Birrer M, Westin SN, Farooq S, Bell-McGuinn KM, Obermayer E, Whalen C, Spagnoletti T, Luo W, Liu H, Hok RC, Aghajanian C, Solit DB, Mills GB, Taylor BS, Won H, Berger MF, Palakurthi S, Liu J, Cantley LC, Winer E. Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer. Ann Oncol. 2017;28(3):512-8. PMID: 29773796.

Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Farooq S, Cadoo K, Whalen C, Luo W, Liu H, Aghajanian C, Solit DB, Mills GB, Taylor BS, Won H, Berger MF, Palakurthi S, Liu JF, Cantley LC, Kaufmann SH, Swisher EM, D'Andrea AD, Winer E, Wulf GM, Matulonis UA. Phase 1 study of the alpha-specific PI3 kinase inhibitor BYL719 and the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in recurrent ovarian and breast cancer: analysis of the dose escalation and ovarian cancer expansion cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACRS; Cancer Res. 2017;77(13 Suppl):Abstract nr CT008.

Shapiro GI, Do KT, Tolaney SM, Hilton JF, Cleary JM, Wolanski A, Beardslee B, Hassinger F, Bhushan K, Cai D, Downey E, Pruitt-Thompson S, Barry SM, Kochupurakkal B, Geradts J, Unitt C, D'Andrea AD, Muzikansky A, Piekarz R, Doyle LA, Supko J. Phase 1 dose-escalation study of the CDK inhibitor dinaciclib in combination with the PARP inhibitor veliparib in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res. 2017;77(13 Suppl):Abstract nr C0147.

de Oliveira Taveira M, Nabavi S, Wang Y, Tonellato P, Esteva FJ, Cantley LC, Wulf GM. Genomic characteristics of trastuzumab-resistant HER2-positive metastatic breast cancer. J Cancer Res Clin Oncol. 2017;143(7):1255-62. PMCID: PMC5486569.

Del Alcazar CG, Huh SJ, Ekram M,  Trinh A, Liu LL, Beca F, Zi X, Kwak M, Bergholtz H, Su Y, Ding L, Russnes HG, Richardson AL, Babski K, Min Hui Kim E, McDonnell C, Wagner J, Rowberry R, Freeman GJ, Dillon D, Sorlie T, Coussens LM, Garber JE, Fan R, Bobolis K, Allred DC, Jeong J, Park SY, Michor F, Polyak K. Immune escape in breast cancer during in situ to invasive carcinoma transition. Cancer Discov. 2017 Jun 26 [Epub ahead of print]. doi: 10.1158/2159-8290.CD-17-0222 PMID: 28652380.

Polak P, Kim J, Braunstein LZ, Karlic R, Haradhavala NJ, Tiao G, Rosebrock D, Livitz D, Kübler K, Mouw KW, Kamburov A, Maruvka YE, Leshchiner I, Lander ES, Golub TR, Zick A, Orthwein A, Lawrence MS, Batra RN, Caldas C, Haber DA, Laird PW, Shen H, Ellisen LW, D'Andrea AD, Chanock SJ, Foulkes WD, Getz G. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Nat Genet. 2017 Aug 21 [Epub ahead of print]. doi: 10.1038/ng.3934. PMID: 28825726