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!
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences