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.
How the Research Was Conducted
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, MA27, conducted by the NCIC Clinical 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 Alliance. The trial mentioned in the study was supported in part by Pfizer, Inc.
Other researchers include Daniel Schaid, Ph.D., Gregory Jenkins, Anthony Batzler, Mohan Liu, Ph.D., Liewei Wang, M.D., Ph.D., Matthew Goetz, M.D., and Richard Weinshilboum, M.D., all of Mayo Clinic; Paul Goss, M.B., BCh, Ph.D. Massachusetts General Hospital Cancer Center, Harvard University; Taisei Mushiroda, Ph.D., Michiaki Kubo, M.D., Ph.D., and Yusuke Nakamura, M.D., Ph.D., RIKEN Center for Genomic Medicine, Tokyo; Judy-Anne Chapman, Ph.D., Lois Shepherd, M.D., and Joseph Pater, M.D., NCIC Clinical Trials Group, Kingston, Ontario; Matthew Ellis, M.B., B.Chir., Ph.D., Washington University, St. Louis; Vered Stearns, M.D., John Hopkins School of Medicine, Baltimore; Daniel Rohrer, M.D., Ohio State University Medical Center, Columbus; Kathleen Pritchard, M.D., Sunnybrook Odette Regional Cancer Centre, University of Toronto; and David Flockhart, M.D., Ph.D., Indiana University, Indianapolis.
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 NCIC Clinical Trials Group (NCIC CTG) 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 NCIC CTG's Central Office is located at Queen's University in Kingston, Ontario, Canada.
Robert Nellis | EurekAlert!
On track to heal leukaemia
18.01.2017 | Universitätsspital Bern
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Power and Electrical Engineering
18.01.2017 | Materials Sciences
18.01.2017 | Life Sciences