Dr. Sparano is Professor of Medicine & Obstetrics, Gynecology, and Women's Health at the Albert Einstein College of Medicine, Associate Chairman for Clinical Research in the Department of Oncology at Montefiore Medical Center, and Associate Director for Clinical Research at the Albert Einstein Cancer Center. He also serves as Vice Chair of the ECOG-ACRIN Research Group and Vice Chair of the AIDS Malignancy Consortium. He is former director of the Hematology-Oncology Fellowship Program at Einstein/Montefiore, co-directs the ECOG-ACRIN Young Investigator Program, and is a faculty member of the Calabresi K12 Oncology Training Program. He is co-principal investigator of the Montefiore-Einstein Minority/Underserved National Community Oncology Research Program (NCORP) grant (in conjunction with Dr. Bruce Rapkin), which funds multicenter, NCI-sponsored clinical trials in cancer therapeutics, cancer prevention/control, and cancer care delivery research. He is also the recipient of funding from the Breast Cancer Research Foundation that is supporting creation of a biospecimen bank designed to identify determinants of late relapse.
Dr. Sparano is a practicing clinician who specializes in medical oncology and clinical and translational cancer research. His research has focused on developmental therapeutic approaches for breast cancer, lymphoma, and HIV-associated cancers, and therapeutic application of molecular profiling in cancer. His research interests are described in greater detail below.
Reducing Overtreatment of Early Stage Breast Cancer
Dr. Sparano serves as the study chair for the TAILORx clinical trial sponsored by National Cancer Institute, the first clinical trial integrating a mulitparameter gene expression assay in clinical decision making for adjuvant therapy with early stage ER-positive, HER2 negative breast cancer (http://www.cancer.gov/clinicaltrials/noteworthy-trials/tailorx), This study completed accrual of approximately 10,000 patients in approximately 900 sites in 4 continents in 2010. Approximately 7000 patients with a mid-range Oncotype DX Recurrence Score (RS 11-25) were randomized to chemoendocrine therapy vs. endocrine therapy alone, whereas the remainder were assigned to endocrine therapy alone if the RS was low (<11), or chemoendocrine therapy if the RS was high (>25). Results from the low risk arm indicate a recurrence rate of only 1% at 5 years with endocrine therapy alone, indicating that these patients may be effectively spared chemotherapy. Results from the group with a mid-range RS randomized endocrine therapy +/- chemotherapy are expected in 2017 or soon thereafter, and the findings will inform the optimal treatment for patients with early stage ER-positive breast cancer, which accounts for about one-half of all breast cancers and 9% of all cancers in the U.S.
- Sparano JA. TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer. 2006 Oct;7(4):347-50. PubMed PMID: 17092406.
- Sparano JA, Paik S. Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol. 2008 Feb 10;26(5):721-8. Review. PubMed PMID: 18258979.
- Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CEJr, Dees EC, Perez EA, Olson JA Jr, Zujewski J, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW. Prospective Validation of a 21-GeneExpression Assay in Breast Cancer. N Engl J Med. 2015 Nov 19;373(21):2005-14.doi: 10.1056/NEJMoa1510764. PubMed PMID: 26412349; PubMed Central PMCID:PMC4701034.
Improving Treatment Outcomes in Breast Cancer
Dr. Sparano is former vice-chair of the ECOG Breast Cancer Committee, and Chair of the ECOG-ACRIN Breast Cancer Committee. In those roles, he has led several phase III NCI-sponsored clinical trials in breast cancer, including a phase III which demonstrated that adjuvant weekly paclitaxel improves overall survival in stage II-III breast cancer (E1199) that has influenced clinical practice internationally. Other analyses of this data set have shown a strong association between obesity and black race with inferior outcomes in ER-positive breast cancer, which has been validated in other reports, and led to additional prospective trials and/or investigations.
- Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. N Engl J Med. 2008 Jul 3;359(1):106. PubMed PMID: 18420499; PubMed Central PMCID: PMC2743943.
- Sparano JA, Wang M, Zhao F, Stearns V, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Race and Hormone Receptor-Positive Breast Cancer Outcomes in a Randomized Chemotherapy Trial. JNatl Cancer Inst. 2012 Jan 16. [Epub ahead of print] PubMed PMID: 22250182. PubMed Central PMCID: PMC3295746.
- Sparano JA, Wang M, Zhao F, Stearns V, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Fetting J, Davidson NE. Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer. Cancer. 2012 Dec 1;118(23):5937-46. doi: 10.1002/cncr.27527. Epub 2012 Aug 27. PubMed PMID: 22926690; PubMed Central PMCID: PMC3586227.
Developing and Validating Gene Expression Signatures in Breast Cancer
Dr. Sparano has collaborated with other investigators to validate and/or refine prognostic gene expression signatures in early stage breast cancer, including the Oncotype Recurrence Score for invasive cancer and DCIS Score for in situ cancer.
- Goldstein LJ, Gray R, Badve S, Childs BH, Yoshizawa C, Rowley S, Shak S, Baehner FL, Ravdin PM, Davidson NE, Sledge GW Jr, Perez EA, Shulman LN, Martino S, Sparano JA. Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol. 2008 Sep 1;26(25):4063-71. Epub 2008 Aug 4. Erratum in: J Clin Oncol. 2009 Jul 20;27(21):3566. PubMed PMID: 18678838; PubMed Central PMCID: PMC2654377.
- Sparano JA, Goldstein LJ, Davidson NE, Sledge GW Jr, Gray R. TOP2A RNA expression and recurrence in estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2012 Jul;134(2):751-7. doi: 10.1007/s10549-012-2112-7. Epub 2012 Jun 16. PubMed PMID: 22706628.PubMed PMID: 23877339; PubMed Central PMCID: PMC3732762.
- Sparano JA, Goldstein LJ, Davidson NE, Sledge GW Jr, Gray R. TOP2A RNA expression and recurrence in estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2012 Jul;134(2):751-7. doi: 10.1007/s10549-012-2112-7. Epub 2012 Jun 16. PubMed PMID: 22706628.
- Solin LJ, Gray R, Baehner FL, Butler SM, Hughes LL, Yoshizawa C, Cherbavaz DB, Shak S, Page DL, Sledge GW Jr, Davidson NE, Ingle JN, Perez EA, Wood WC, Sparano JA, Badve S. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2013 May 15;105(10):701-10. doi: 10.1093/jnci/djt067. Epub 2013 May 2. PubMed PMID: 23641039; PubMed Central PMCID: PMC3653823.
Evaluating Interaction between Breast Cancer and the Microenvironment
As co-program leader of the Einstein Cancer Center Tumor Micoenvironment Program along with Dr. John Condeelis, Dr. Sparano has collaborated with a multidisciplinary team at Einstein and Montefiore to validate a novel biomarker called ”TMEM” (Tumor Microenvironment of Metastasis), which provides complementary prognostic information to other markers (eg, IHC4) in ER-positive breast cancer. He is currently working with the team to evaluate novel agents which may prevent TMEM assembly and/or function, and hence prevent metatasis. He also collaborates with Dr. Xingxing Zang in evaluating the B7 family of proteins in breast cancer, and with Dr. Thomas Rohan (Chair, Dept. of Epidemiology & Populaton Health) to evaluate other prognostic and predictive biomarkers .
- Rohan TE, Xue X, Lin HM, D'Alfonso TM, Ginter PS, Oktay MH, Robinson BD, Ginsberg M, Gertler FB, Glass AG, Sparano JA, Condeelis JS, Jones JG. Tumor microenvironment of metastasis and risk of distant metastasis of breast cancer. J Natl Cancer Inst. 2014 Jun 3;106(8). pii: dju136. doi: 10.1093/jnci/dju136. Print 2014 Aug. PubMed PMID: 24895374. PMCID Pending.
- Jeon H, Vigdorovich V, Garrett-Thomson SC, Janakiram M, Ramagopal UA, Abadi YM, Lee JS, Scandiuzzi L, Ohaegbulam KC, Chinai JM, Zhao R, Yao Y, Mao Y, Sparano JA, Almo SC, Zang X. Structure and cancer immunotherapy of the B7 family member B7x. Cell Rep. 2014 Nov 6;9(3):1089-98. doi: 10.1016/j.celrep.2014.09.053. Epub 2014 Oct 30. PubMed PMID: 25437562; PubMed Central PMCID: PMC4250833.
- Janakiram M, Chinai J, Fineberg S, Fiser A, Montagna C, Medaverepu R, Castano E, Jeon H, Ohaegbulam KC, Zhao R, Zhao A, Almo S, Sparano JA, Zang X. Expression, clinical significance, and receptor identification of the newest B7 family member HHLA2 protein. Clin Cancer Res. 2014 Dec 30. pii: clincanres.1495.2014. [Epub ahead of print] PubMed PMID: 25549724.
Integrating Novel Therapeutics with Standard Therapies in Localized and Advanced Stage Breast cancer
Dr. Sparano has led several clinical trials testing novel agents in combination with standard neoadjuvant therapy, including farnesyl transferase inhibitors, histone deacetylase inhibitors, and m-TOR inhibitors.
- Sparano JA, Moulder S, Kazi A, Coppola D, Negassa A, Vahdat L, Li T, Pellegrino C, Fineberg S, Munster P, Malafa M, Lee D, Hoschander S, Hopkins U, Hershman D, Wright JJ, Kleer C, Merajver S, Sebti SM. Phase II trial of tipifarnib plus neoadjuvant doxorubicin-cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer. Clin Cancer Res. 2009 Apr 15;15(8):2942-8. Epub 2009 Apr 7. PubMed PMID: 19351752; PubMed Central PMCID: PMC2785076.
- Andreopoulou E, Vigoda IS, Valero V, Hershman DL, Raptis G, Vahdat LT, Han HS, Wright JJ, Pellegrino CM, Cristofanilli M, Alvarez RH, Fehn K, Fineberg S, Sparano JA. Phase I-II study of the farnesyl transferase inhibitor tipifarnib plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in HER2/neu-negative inflammatory carcinoma and non-inflammatory estrogen receptor-positive breast carcinoma. Breast Cancer Res Treat. 2013 Oct;141(3):429-35. doi: 10.1007/s10549-013-2704-x. Epub 2013 Sep 26. PubMed PMID: 24068539; PubMed Central PMCID: PMC3999640.
- Tu Y, Hershman DL, Bhalla K, Fiskus W, Pellegrino CM, Andreopoulou E, Makower D, Kalinsky K, Fehn K, Fineberg S, Negassa A, Montgomery LL, Wiechmann LS, Alpaugh RK, Huang M, Sparano JA. A phase I-II study of the histone deacetylase inhibitor vorinostat plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced breast cancer. Breast Cancer Res Treat. 2014 Jul;146(1):145-52. doi: 10.1007/s10549-014-3008-5. Epub 2014 Jun 6. PubMed PMID: 24903226.
Developing More Effective Therapies for HIV-Associated Cancers
Dr. Sparano serves as the current vice-chair of the AIDS Malignancy Consortium (AMC), and prior chair of the AMC Lymphoma Working Group and Non-AIDS Defining Malignancy Working Group. In these roles, he has developed novel therapeutic approaches for the management of HIV-associated lymphoma (rituximab plus EPOCH) and anal cancer (cetuximab plus cisplatin/5-FU/RT), and organized an international team in collaboration with Dr. Stefan Barta to perform a metaanalysis of HIV-lymphoma trials, and a new prognostic score for HIV-associated lymphoma.
- Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, and Mitsuyasu R. ; Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated, B-cell non-Hodgkin's lymphoma. Blood, Dec 2009; doi:10.1182/blood-2009-08-231613 PMCID: PMC2636875
- Barta SK, Xue X, Wang D, Tamari R, Lee JY, Mounier N, Kaplan LD, Ribera JM, Spina M, Tirelli U, Weiss R, Galicier L, Boue F, Wilson WH, Wyen C, Oriol A, Navarro JT, Dunleavy K, Little RF, Ratner L, Garcia O, Morgades M, Remick SC, Noy A, Sparano JA. Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients. Blood. 2013 Nov 7;122(19):3251-62. doi: 10.1182/blood-2013-04-498964. Epub 2013 Sep 6. Review. PubMed PMID: 24014242; PubMed Central PMCID: PMC3821722.
- Barta SK, Xue X, Wang D, Lee JY, Kaplan LD, Ribera JM, Oriol A, Spina M, Tirelli U, Boue F, Wilson WH, Wyen C, Dunleavy K, Noy A, Sparano JA. A new prognostic score for AIDS-related lymphomas in the Rituximab-era. Haematologica. 2014 Aug 22. pii: haematol.2014.111112. [Epub ahead of print] PubMed PMID:25150257.
- Sparano JA, Lee JY, Palefsky J, Henry DH, Wachsman W, Rajdev L, Aboulafia D,Ratner L, Fitzgerald TJ, Kachnic L, Mitsuyasu R. Cetuximab Plus Chemoradiotherapy for HIV-Associated Anal Carcinoma: A Phase II AIDS Malignancy Consortium Trial. J Clin Oncol. 2016 Dec 12:JCO2016691642. [Epub ahead of print] PubMed PMID:27937092.
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