Canadian Cancer Trials Group Bulletins

General


Two Recent Publications

MA.27 -- A Genome-Wide Association Study in Patients Experiencing Musculoskeletal Adverse Events on Aromatase Inhibitors as Adjuvant Therapy in Early Breast Cancer Entered on Canadian Cancer Trials Group Trial MA.27. A Pharmacogenetics Research Network-RIKEN Collaboration.

Ingle JN, Schaid DJ, Goss PE, Liu M, Mushiroda T, Chapman J-AW, Kubo M, Jenkins GD, Batzler A, Shepherd L, Pater J, Wang L, Ellis MJ, Stearns V, Rohrer DC, Goetz MP, Pritchard KI, Flockhart DA, Nakamura Y, Weinshilboum RM. Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors (ONLINE). J Clin Oncol 2010.

http://jco.ascopubs.org/content/early/2010/09/24/JCO.2010.28.5064

The accompanying editorial (link below), indicates "the results of the study are scientifically
important and serve to establish a new paradigm for the potential power of pharmacogenomics in oncology".

http://jco.ascopubs.org/content/early/2010/09/24/JCO.2010.31.2926

Following is a press release issued by the Mayo Clinic in Rochester, MN, home institution of the lead author, Dr. James Ingle:

Mayo Collaboration Finds Source of Breast Drug Side Effect
Pharmacogenomic discovery allows for improved cancer therapy

ROCHESTER, Minn. -- Mayo Clinic researchers and their international colleagues have discovered genetic variants that lead to severe arthritis for a subset of women when taking aromatase inhibitors to treat their breast cancer. This serious side effect is so painful that many women halt their lifesaving medication. The findings appear today in the online issue of Journal of Clinical Oncology.

"Many women stop taking aromatase inhibitors due to the accompanying joint pain," says James Ingle, M.D., Mayo Clinic oncologist and senior author of the study. "We used the latest genetic technology in a very large group of women and discovered totally new clues to the cause of the main reason women stop this potentially lifesaving drug. Our findings open the door to finding ways to identify women who will develop these side effects and treat those who do, thus allowing more women to take this therapy and decrease their chances of breast cancer recurrence." Aromatase inhibitors are most often used as adjuvant therapy for postmenopausal women with early stage breast cancer.

The researchers -- including investigators from the United States, Canada and Japan -- conducted a genome-wide association study to identify gene variants called single nucleotide polymorphisms (SNPs) that are associated with musculoskeletal pain. They selected patients who were enrolled in a prospective clinical trial, MA.27, conducted by the Canadian Cancer Trials Group in Canada in collaboration with the NCI-sponsored North American Breast Cancer Groups comparing two aromatase inhibitor drugs. Two controls were matched with each patient and each patient who was selected experienced arthritis-like side effects within the first two years of treatment, or had already dropped out of the trial because of the pain. Researchers studied 293 separate cases, comparing them to 585 controls.

They found four likely SNPs on chromosome 14, all of which were nearest the gene T-Cell Leukemia 1A, which they discovered also was estrogen dependent. One of the SNPs also created an estrogen response with increased gene expression after exposure to estradiol, a widely used post-menopausal treatment. The results provide researchers with genetic markers for the aromatase inhibitor-induced arthritis and clues to find ways to treat it.
###
Support for the study came from the National Institutes of Health (NIH), the Canadian Cancer Society, the Biobank Japan Project funded by the Ministry of Education, Culture, Sports, Science and Technology, and the Breast Cancer Research Foundation. Other support was provided by the NIH Pharmacogenomics Research Network and the RIKEN Center for Genomic Medicine Global A zer, Inc.

About Mayo Clinic
For more than 100 years, millions of people from all walks of life have found answers at Mayo Clinic. These patients tell us they leave Mayo Clinic with peace of mind knowing they received care from the world's leading experts. Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. At Mayo Clinic, a team of specialists is assembled to take the time to listen, understand and care for patients' health issues and concerns. These teams draw from more than 3,700 physicians and scientists and 50,100 allied staff that work at Mayo Clinic┐s campuses in Minnesota, Florida, and Arizona; and community-based providers in more than 70 locations in southern Minnesota, western Wisconsin and northeast Iowa. These locations treat more than half a million people each year. To best serve patients, Mayo Clinic works with many insurance companies, does not require a physician referral in most cases and is an in-network provider for millions of people. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education, visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your general health information.

The Canadian Cancer Trials Group (Canadian Cancer Trials Group) is a cancer clinical trials cooperative group that conducts phase I-III trials testing anti-cancer and supportive therapies across Canada and internationally. It is one of the national programmes and networks of the Canadian Cancer Society Research Institute (CCSRI), and is supported by the CCSRI with funds raised by the Canadian Cancer Society (CCS). The Canadian Cancer Trials Group's Central Office is located at Queen's University in Kingston, Ontario, Canada.

____________________________________________

OV.13 -- An International Multi-Centre Randomized Phase III Study Comparing Upfront Debulking Surgery Versus Neo-Adjuvant Chemotherapy in Patients with Stage IIIC or IV Epithelial Ovarian Cancer.

Verleye L, Ottevanger PB, Kristensen GB, Ehlen T, Johnson N, van der Burg MEL, Reed NS, Verheijen RHM, Gaarenstroom KN, Mosgaard B, Seoane JM, van der Velden J, Lotocki R, van der Graaf W, Penninckx B, Coens C, Stuart G, Vergote I. Quality of pathology reports for advanced ovarian cancer: Are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial (ONLINE). Eur J Can 2010.

http://www.ejcancer.info/article/S0959-8049%2810%2900820-8/abstract