Dr. Joseph Ragaz

Medical Oncologist & Clinical Professor
Faculty of Medicine
School of Population & Public Health
The University of British Columbia, Vancouver, BC, Canada



Academic Research Activities


Dr. Ragaz initiated the clinical research activities in the late 1970’s at the British Columbia Cancer Agency (BCCA), University of British Columbia, Vancouver, BC. These continued between his 2003 – 2008 tenure at the McGill University, Montreal, PQ, and currently [2012] through the School of Population and Public Health, University of British Columbia.

Summary

2006 - 2012 [present] Cancer Outcome Projects - CANADA. Long-term Breast Cancer Incidence & Mortality trends in the Provinces of Canada, correlating outcomes with the organization of cancer care (collaboration: Public Health Agency of Canada, Canadian Cancer Registry and Statistics Canada).

2008 - 2012 [present]. Cancer Outcome Projects - CHINA. Comparative analyses of Breast Cancer Incidence and Mortality trends between urban and rural China (Collaboration: Cancer Registries in Shanghai & Qidong & International Agency for Research on Cancer [IARC], Lyon, France).

2009 – 2012 [present]: Molecular classification of breast cancer tumors. Cost–benefit analyses and the overall impact of a new guideline proposal where chemotherapy would be restricted to breast cancer patients without documented chemotherapy resistance [as determined on molecular classification of the tumor sample at diagnosis].

2009 – 2012 Breast Cancer Prevention – Analyses of key Breast Cancer Prevention Initiatives and logistics of their implementation in British Columbia and Canada.

2000 – 2012. HRT reviews. Since the 1990’s, Dr. Ragaz and his team have been monitoring, and at times providing additional analyses of HRT data to clarify the strengths and shortcomings of existing trials and identify issues responsible for the lack of clarity of the HRT data. (SABCS presentation 2010 (PDF) )

2006 – 2012. Impact of Cox2 and Aromatase Inhibition  in Breast Cancer treatment and Cancer Prevention.

1997 - 2005. Post-Mastectomy Radiation therapy. This seminal British Columbia randomized trial coordinated by Dr. Ragaz and his team (New England Journal of Medicine, 1997; Journal of National Cancer Institute, 2005) helped to change in the late 1990s, along with a similarly designed Danish trial, the post-mastectomy radiation therapy guidelines for stage I-II breast cancer.

2000 - 2004. First phase of the BCCA Molecular Biology project of Tissue Microarrays. Start and completion of the first phase of the BCCA Tissue Microarray project, in collaboration with the UBC Pathology Group [GPEC] and several groups of international collaborators [Drs. M. Lippman, G. Sledge, K. Miller, S. Badwe, A. Brodie, A. Harris, et al.]. This project correlated, in 930 patients participating in British Columbia Breast cancer trials, the 20 year survival outcome according to the expression of novel molecular markers: Her2/Neu, VEGF, Cox2, uPA, Aromatase, EMSY, etc.

1990 - 2000. Breast Cancer Outcome unit. In the late 1980s, Dr. Ragaz and his team conceptualized and obtained funding for the British Columbia Breast Cancer Outcome Unit – soon afterwards becoming one of the largest and most active Clinical Breast Cancer Outcome units in North America.

1977-1985. Neoadjuvant Therapy Program for early Breast cancer was piloted by Dr. Ragaz' team in British Columbia, and eventually led to the guideline-acceptance of Neo-Adjuvant therapy for Breast Cancer in North America and Europe. Dr. Ragaz and has team presented data recently indicating Neoadjuvant setting as an ideal one to test new agents for cancer efficacy, substantially reducing the time required in testing & activating new agents into guidelines. [Ragaz, J.: Randomized Trials in Oncology: a necessity or time-consuming luxury. Breast Cancer Res. 2010]

1978 - 1980. Aromatase Inhibitors with Medical Adrenalectomy (Aminoglutethimide) in British Columbia and Canada. One of the first international projects of Aromatase Inhibitors for breast cancer therapy.

Selected Publications

Cancer Epidemiology: Organization of cancer care

J. Ragaz, K.S. Wilson, H. Wong, G. Muraca, W. Hryniuk, C. Bajdik: Molecular classification with 21 gene assay (Oncotype DX®) shows in 196,967 ER positive patients high frequency of low Recurrence Score [LRS] in both node positive (N+) and negative (N-) breast cancer (BrCa) cohorts. Definition of chemo resistance based on LRS with cost and guideline implications. Cancer Research, 2011, Vol .71; 135s

Ragaz, J. : The 21 gene assay: Impact on breast cancer in Canada. Ethically and economically when do we act? Cancer Advocacy coalition of Canada, March 2010, the 2009-2010 Report Card.

Ragaz, J.: Randomized adjuvant trials in Oncology: A necessity or time-consuming luxury? Breast Cancer Research 2010, 12(Suppl 4):S14.

Ragaz, J. : The 21-gene assay and its impact on breast cancer in Canada. Oncology Exchange, May 2010.

Cancer Epidemiology - Breast Cancer Incidence and Mortality Trends, Canada & China

Ragaz, J., Spinelli, J.J, Semeniciw, R., Hryniuk, W., Budlovsky, J., Franco, E.: Breast cancer mortality reduction in the western world: therapeutic versus diagnostic interventions. Implications for cancer care organization processes. Cancer Research, Vol 69; Supl; January 2009; p383s # 6083.

Ragaz, J., Wong, H.; Qian, H.: Comparative analysis of Breast Cancer (BrCA) mortality reduction among Regions of Canada between 1950 and 2004: Impact of systemic and diagnostic guidelines after 1977, with Model definition of Potentially avoided Annual deaths. Cancer Research 2009, Vol. 69, pp 613s.

Ragaz, J.; Bao, P.P.; Pisani, P.; Zheng, Y.: Breast Cancer Mortality Trends in the Westcompared to the East: Lives gained, Lives lost. Cancer Research, Vol 69; January 2009; p383s

Ragaz, J., Chen, G.; Bao, P.P.; Hu, X.H.; Zheng, Y.; Wong, K.; Qian H.: Rapid Increase in Breast Cancer (BrCa) with Regional Mortality Differences in China: Adverse effects of the Westernization and benefits of the Western interventions. JCO, 2009, Suppl., ASCO, Breast, Sept. 2009.

Ragaz, J.; Spinelli, J.J; Villeneuve, G.; Ellison, L.; Coldman, A.: Mortality reduction of breast cancer in Canada: Impact of cancer care infrastructure. JCO, 2005, Vol. 23; (No. 16S): p40.

Hormone Replacement Therapy (HRT)

Ragaz, J., Shakeraneh, S.: Estrogen Prevention of Breast Cancer: A Critical Review. In: Estrogen Preventiono f Breast Cancer; S. Suba [ed]., Nova Science, New York, 2012, in press.

Ragaz, J., Budlovsky, Joshua : Hormone Replacement Therapy: A critical Review. In: Manual of Breast Disease; I Jatoi, E. Kaufmann (eds.), Springer-Verlag, New York 2010, pp 451 - 473.

J. Ragaz, J. Budlovsky, J.J. Spinelli, N. Le : Protective effect of Estrogen (E2) alone and increased risk of E2 plus Progestins on Breast Cancer. The 2009 review of the Women’s Health Initiative HRT Published trials. Cancer Research, 2009, Vol. 69, N 24, pp 533s.

Ragaz, J. : Hormone replacement therapy in patients with a prior breast cancer history: A critical review. In: Manual of Breast Disease. (ed.) Ismail Jatoi. Lippincott Williams & Wilkins, 2002, 389-415.

Ragaz, J., Coldman, A. : Age-matched all cause-mortality impact of hormone replacement therapy (HRT): Applicability to breast cancer survivors. Breast Ca Res Treat 57-58 A23, 1999.

Molecular Biology aspects of Breast Cancer & the First British Columbia Tissue Miocroarray Project

Zhao, X., Xu, X., Guo, L., Ragaz, J., Guo, H., Wu, J., et al. : Biomarker alterations with metronomic use of low-dose zoledronic acid for breast cancer patients with bone metastases and potential clinical significance. Breast Cancer Res Treat. 2010 Sep 30. (Epub ahead of print) PMID: 20882405 [PubMed].

Ragaz, J., Spinelli, J.J : Cost-benefit estimates of Adjuvant (Adj) Trastuzumab (Herceptin, H) for early Breast Cancer (BrCa). Breast Ca Res & Treat 2005; 94: S 93.

Ragaz, J. : Impact of HER-2/neu expression on natural history and outcome of human breast cancer. Breast diseases, J. Harris, M. Morrow, M. Lippman, K. Osborne, eds., Lippincott Williams and Wilkins, June 2004.

Ragaz, J., Simpson-Herren, L., Lippman, M., Fisher, B. : Questions related to the effects of therapy on biology and kinetics of the surviving tumor. [Journal Article] Progress in Clinical & Biological Research. 354A:1-6, 1990. UI: 2247483

Callagy, G.M., Pharoah, P.D., Pinder, S.E., Hsu, F.D., Nielsen, T.O., Ragaz, J., Ellis, I.O., Huntsman, D., Caldas, C. : Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. [erratum appears in Clin Cancer Res. 2006 Aug 15;12(16):5002]. [Journal Article. Research Support, Non-U.S. Gov't] Clinical Cancer Research. 12(8):2468-75, 2006 Apr 15. UI: 16638854

Long, B.J., Jelovac ,D., Handratta, V., Thiantanawat, A., MacPherson, N., Ragaz, J., Goloubeva, O.G., Brodie, A.M. : Therapeutic strategies using the aromatase inhibitor letrozole and tamoxifen in a breast cancer model. Journal of the National Cancer Institute. 96(6):456-65, 2004 Mar 17.

Nielsen, T.O., Hsu, F.D., Jensen, K., Cheang, M., Karaca, G., Hu, Z., Hernandez-Boussard, T., Livasy, C., Cowan, D., Dressler, L., Akslen, L.A., Ragaz, J., Gown, A.M., Gilks, C.B., van de Rijn, M., Perou,C.M. : Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clinical Cancer Research. 10(16):5367-74, 2004 Aug 15. UI: 15328174

Hughes-Davies, L., Huntsman, D., Ruas, M., Fuks, F., Bye, J., Chin, S.F., Milner, J., Brown, L.A., Hsu, F., Gilks, B., Nielsen, T., Schulze, M., Chia, S., Ragaz, J. et al. : EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer.[see comment]. Cell. 115(5):523-35, 2003 Nov 26. UI: 14651845

Nielsen, T.O., Andrews, H.N., Cheang,M., Kucab, J.E., Hsu, F.D., Ragaz, J. et al. : Expression of the insulin-like growth factor I receptor and urokinase plasminogen activator in breast cancer is associated with poor surviva. Cancer Research. 64(1):286-91, 2004 Jan 1. UI: 14729636

Ragaz, J., Miller, K., Badve, S., Dayachko, Y., Dunn, S., Nielsen, T., Brodie, A., Huntsman, D., Bajdik, C., Sledge, G. : Adverse association of expressed vascular endothelial growth factor (VEGF), Her-2, Cox-2, uPA and EMSY with long-term outcome of Stage I-III breast cancer (BrCA). J Clin Oncology; Suppl. 2004 July 15; Vol. 22 p. 14S.

J.Ragaz, C. Bajdik, J.J. Spinelli, M. Hayes, D. Jelacic, A. Brodie.: Significant expression of Cox-2 according to Aromatase. Long-term follow up of the British Columbia Tissue Microarray project. Breast Ca Res Treat 2004; Vol.88; #109; S22.

Radiotherapy in Early Breast Cancer

Ragaz, J.: Radiation impact in breast cancer. Breast Cancer Res. 2009;11 Suppl 3:S14. Epub 2009 Dec 18. Review, pp 1-5.

Ragaz, J., Olivotto, I.A., Spinelli, J.J., et al.: Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. Journal of the National Cancer Institute (the JNCI). 97(2):116-26, 2005 Jan 19.

Ragaz, J., Jackson, S.M., Le, N., Plenderleith, I.H., Spinelli, J.J., et al.: Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer.[see comment]. [Clinical Trial. Journal Article. Randomized Controlled Trial] New England Journal of Medicine. 337(14):956-62, 1997 Oct 2. UI: 9309100

Ragaz, J., Spinelli, J.J., Coldman, A.J.: Breast cancer survival advantage with radiotherapy. Lancet. 356(9237):1270-71, 2000 Oct 7. UI: 11072966

Ragaz, J., Spinelli, J.J.: Wide-field radiation as adjunct to adjuvant chemotherapy in high-risk cases with early breast cancer: do it or not?[comment].[Journal Article] International Journal of Cancer. 87(3):423-6, 2000.

Ragaz, J., Jackson, S.M.: Significance of axillary lymph node extranodal soft tissue extension and indications for postmastectomy irradiation. Cancer 2000. 89(1):223-5.

Ragaz, J., Spinelli, J.J.: Large breast cancer tumors and radiotherapy: biology vs. chronology.[comment]. [Comment. Editorial] Radiotherapy & Oncology. 1999; 52(3):203-5.

Neoadjuvant Therapy of Breast Cancer

Ragaz, J., Goldie, J.H., Baird, R., Rebbeck, P., Basco, V., Coldman, A. : Experimental basis and clinical reality of preoperative (neoadjuvant) chemotherapy in breast cancer. [Journal Article] Recent Results in Cancer Research. 115:28-35, 1989.

Ragaz, J. : Preoperative (neoadjuvant) chemotherapy for breast cancer: outline of the British Columbia Trial. [Clinical Trial. Comparative Study. Journal Article] Recent Results in Cancer Research. 103:85-94, 1986.

Ragaz, J. : Emerging modalities for adjuvant therapy of breast cancer: neoadjuvant chemotherapy. [Clinical Trial. Journal Article. Randomized Controlled Trial] NCI Monographs. (1):145-52, 1986.

Ragaz, J., Baird, R., Rebbeck, P., Goldie, J., Coldman, A., Spinelli, J. : Neoadjuvant (preoperative) chemotherapy for breast cancer. [Journal Article] Cancer. 56(4):719-24, 1985 Aug 15.

Oxford Overview Meta-analyses of Early Breast Cancer trials, 1985 - 2005

Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet; Volume 366, Issue 9503, 17 December 2005-6 January 2006, Pages 2087-2106.

Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Polychemotherapy for early breast cancer: An overview of the randomized trials. Lancet; 09/19/1998, Vol. 352 Issue 9132, p930-942

The impact of Tamoxifen in prevention of human Breast Cancer

Ragaz, J., Spinelli, J.J.; Coldman, A. ; Mihalciou, C.: Is Tamoxifen prevention of Breast Cancer (BrCa) underutilized in younger women? Analysis of competing cause mortality. Journal Clin Oncol, Suppl., 2006; Vol. 24; p 39.

Ragaz, J. : Interaction of tamoxifen's impact on overall net mortality and quality of life. Oncology. 1(2 Suppl 1):45-8, 1997 Feb.

Ragaz, J., Coldman, A. : Survival impact of adjuvant tamoxifen on competing causes of mortality in breast cancer survivors, with analysis of mortality from contralateral breast cancer, cardiovascular events, endometrial cancer, and thromboembolic episodes. Journal of Clinical Oncology. 16(6):2018-24, 1998.

Breast Cancer Outcomes [BCCA Breast Cancer Outcome Unit]

Woodward, W.A, Truong, P.T, Yu, T.K, Tereffe, W., Oh, J., Perkins, G., Strom, E., Meric-Bernstam, F., Gonzalez-Angulo, A.M, Speers, C., Ragaz J., Buchholz, T.A: Among women who experience a recurrence after postmastectomy radiation therapy irradiation is not associated with more aggressive local recurrence or reduced survival. Breast Cancer Res Treat. 2010 Sep;123(2):597-605.

Truong, P.T., Woodward, W.A., Thames, H., Ragaz, J., et al.: The ratio of positive to excised nodes identifies high-risk subsets. [Comparative Study. Journal Article. Multicenter Study. Randomized Controlled Trial] International Journal of Radiation Oncology, Biology, Physics. 68(1):59-65, 2007 May 1.

Chua, B., Olivotto, I., Weir, L., Kwan,W., Truong, P., Ragaz, J.: Increased use of adjuvant regional radiotherapy for node-positive breast cancer in British Columbia. [Journal Article. Research Support, Non-U.S. Gov't] Breast Journal. 10(1):38-44, 2004 Jan-Feb.

Bryce, C., Kennecke, H., Chia,S., Ragaz, J. : Benefit of Paclitaxel in estrogen receptor-negative versus estrogen receptor-positive early breast cancer. Journal of Clinical Oncology. 21(23):4465- 66, 2003 Dec 1.

Olivotto,I.A., Chua, B., Allan, S.J., Speers, C.H., Chia, S., Ragaz, J. : Long-term survival of patients with supraclavicular metastases at diagnosis of breast cancer. [Journal Article] Journal of Clinical Oncology. 21(5):851-4, 2003.

Aromatase inhibitors in Breast Cancer

Ragaz, J. : Status of aromatase inhibitors in relation to other breast cancer treatment modalities. [Review] [145 refs] [Journal Article. Review] Endocrine-Related Cancer. 6(2):277-91, 1999 Jun.

Ragaz, J., Buskard, N., Manji, M. : Thrombocytopenia after combination therapy with aminoglutethimide and tamoxifen: which drug is to blame?. [Case Reports. Journal Article] Cancer Treatment Reports. 68(7-8):1015-6, 1984 Jul-Aug.



BOOKS

Ragaz, J., Simpson-Herren, L., Lippman, M., Fisher, B. eds. : Effects of Therapy on the Biology and Kinetics of the Surviving Cancer. Preclinical, Basic Research - Part A. Willey-Liss, New York, 1990.

Ragaz, J., Simpson-Herren, L., Lippman, M., Fisher, B. eds. : Effects of Therapy on the Biology and Kinetics of the Surviving Cancer. Clinical - Part B. Willey-Liss, New York, 19901. Ragaz, J., Ariel I., eds: High Risk Breast Cancer – Diagnosis. Springer-Verlag, Heidelberg, 1989.

Ragaz, J., Ariel, I., eds. : High Risk Breast Cancer – Therapy. Springer-Verlag, Heidelberg, 1991.

Ragaz, J., Band, P., Goldie, J.H., eds. : Preoperative (Neoadjuvant) Therapy of Cancer. Springer-Verlag, Heidelberg, 1986.



CHAPTERS

Ragaz, J., Shakeraneh, S.: Estrogen Prevention of Breast Cancer: A Critical Review. In: Estrogen Prevention of Breast Cancer; S. Suba [ed]., Nova Science, New York, 2012, in press.

Ragaz, J., Budlovsky, J. : Hormone Replacement Therapy: A critical Review. In: Manual of Breast Disease; I. Jatoi, E. Kaufmann (eds.), Springer-Verlag, New York 2010, pp 451 - 473.

Ragaz, J. : Impact of HER-2/neu expression on natural history and outcome of human breast cancer. Breast diseases, J. Harris, M. Morrow, M. Lippman, K. Osborne, eds., Lippincott, Williams and Wilkins, June 2004.

Ragaz, J., Spinelli, J.J. : Survival impact of locoregional radiation in Stage I-II breast cancer: Evidence-based review. In: Breast Cancer Management: Application of clinical and translational evidence to patient care. Second edition; J.M. Nabholtz, K. Tonkin, D. Reese, M. Apro, A. Buzdar eds., W.W. Lippincott, New York, 2002.

Ragaz, J., Jackson, S. : Survival gains of locoregional radiation in early breast cancer. (eds) Nabhotz, M., Tonkin,K., Aapro, M.S., Buzdar, A.U. Martin Dunitz 2000; 285. Ragaz, J., Coldman, A., Salinas, F., Worth, A., Manji, M., Goldie, J.H. : Preoperative Chemotherapy of Cancer. In Breast Cancer, I. Ariel, B. Cleary eds., McGraw Hill, New York; 312-328; 1986.

Ragaz, J. : Hormone replacement therapy in patients with a prior breast cancer history: A critical review. In: Manual of Breast Disease. (ed) Ismail Jatoi. Lippincott Williams & Wilkins, 2002, 389-415.

Developmental Aspects of High Risk Breast Cancer Therapy. In: High Risk Breast Cancer, J. Ragaz, I.M. Ariel (eds), Springer-Verlag, New York, Heidelberg, 493-511, 1991.

Ragaz, J. : Role of Preoperative Therapy in High Risk Breast Cancer: Review. In: High Risk Breast Cancer. J. Ragaz, I.M. Ariel (eds), Springer-Verlag, New York, Heidelberg, 71-85, 1991.

Ragaz, J., Ariel, I.M. : Therapeutic Highlights of High Risk Breast Cancer: Comments Related to Surgery, to Radiotherapy and Hormone Therapy. In: High Risk Breast Cancer – Therapy, J. Ragaz, IM Ariel (eds), Springer-Verlag, New York Heidelberg 2-25, 1991.

Ragaz, J. : Review of the Effects of Therapy and Biology in Kinetics of Surviving Tumor Part I. In: Effects of Therapy on Biology and Kinetics of the Residual tumor Part A: Preclinical Aspects, J. Ragaz, L. Simpson-Herren, M.E. Lippman, B. Fisher (eds), Wiley-Liss, 7-21; 1990.

Ragaz, J. : Comments on kinetics and biology of the residual cancer and on relevant therapeutic strategies based on these phenomena. Part I and II. In: Progress in Clinical and Biological Research, Wiley-Liss, New York, Volume 354 A and B: 117-141, 19

Ragaz, J. : Comments on future developments of cancer therapy taking into consideration tumor biology and kinetics. Part I and II. In: Progress in Clinical and Biological Research, Wiley-Liss, New York, volume 354 A and B: 379-387, 1990.

Ragaz, J., Ariel, I.M. : High risk breast cancer: Definition of the risk. In: High Risk Breast Cancer. J. Ragaz, I.M. Ariel (eds), Springer-Verlag (Heidelberg), 3-25; 1989.

Ragaz, J., Goldie, J.H., Baird, R., et al : Experimental Basis and Clinical Reality of Preoperative (Neoadjuvant) Chemotherapy in Breast Cancer. In: Recent Results in Cancer Research, Springer-Verlag (Heidelberg), 115: 28-351; 1989.

Ragaz, J., Manji, M., Olivotto, I., Knowling, M., Basco, V., Plenderleith, I. : Preoperative Combined Modality (Neoadjuvant) Therapy of Locally Advanced Breast Cancer. In Fundamental Problems in Breast Cancer. Patterson, A.H.G., Lee, A., eds., Martinus Nijhof, 1987, 383-391.

Ragaz, J. : Management of Stage III Breast Cancer: New Developments. In Endocrine Related Breast Cancer, B. Stoll Ed.; 1986.

Rootman J., Ragaz, J., Cline, R., Lapointe, J. : Metastatic and Secondary Tumors of the Orbit. In J. Rootman Ed.: Diseases of the Orbit 1987.