Navigation Links
Genetic variations may help identify best candidates for preventive breast cancer drugs

ROCHESTER, Minn. -- Newly discovered genetic variations may help predict breast cancer risk in women who receive preventive breast cancer therapy with the selective estrogen receptor modulator drugs tamoxifen and raloxifene, a Mayo Clinic-led study has found. The study is published in the journal Cancer Discovery.

"Our findings are important because we identified genetic factors that could eventually be used to select women who should be offered the drugs for prevention," said James Ingle, M.D., an oncologist at Mayo Clinic.

Dr. Ingle and collaborators at the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the RIKEN Center for Genomic Medicine conducted a genome-wide association study involving 592 patients who developed breast cancer while receiving preventive therapy and 1,171 matched controls. Participants were selected from 33,000 women enrolled in the NSABP breast cancer prevention trials. This research was supported by a Pharmacogenomics Research Network grant from the National Institute of General Medical Science and the National Cancer Institute.

The researchers analyzed participants' DNA to identify variations in their genetic makeup and identified two genetic variations, or single nucleotide polymorphisms (SNPs), that were associated with breast cancer risk in or near the genes ZNF423 and CTSO.

They discovered that women with favorable variations in these genes were more likely to respond to preventive therapy with the drugs while women with unfavorable variations may not. In addition, women with unfavorable variations had a five-fold increased risk of developing breast cancer.

Dr. Ingle says the recent guidelines by the U.S. Preventive Services Task Force emphasize that selective estrogen receptor modulators (SERM) therapy with tamoxifen and raloxifene can lower a woman's risk for developing breast cancer. However, there currently is no way to know which women will benefit from the therapy.

"This is a major step toward truly individualized prevention of breast cancer," says Dr. Ingle. "Our findings provide clear direction as to which women are likely and which are unlikely to benefit from tamoxifen or raloxifene." Dr. Ingle says the findings provide the basis for a reinvigoration of research efforts in breast cancer prevention.

The researchers also studied breast cancer cell lines with the most common variation and the less common variation of the SNPs. They found that in cells with the most common variation of the SNPs, estrogen increased expression of both ZNF423 and CTSO and the expression of BRCA1, a gene associated with breast cancer risk. Estrogen did not increase expression of these genes in cells that had the less common form of the SNPs. Importantly, however, when tamoxifen or raloxifene were added to estrogen, there was a striking reversal in the patterns of expression of ZNF423 and BRCA1. In cells with the less common ZNF423 SNP, expression of ZNF423 and BRCA1 rose dramatically. This reversal in expression patterns provides a potential explanation for the decreased occurrence of breast cancer in women undergoing SERM therapy who carry this SNP.


Contact: Joe Dangor
Mayo Clinic

Related medicine news :

1. IntegraGen launches ARISk test, a genetic screening tool for autism in high-risk children
2. 2 genetic deletions in human genome linked to the development of aggressive prostate cancer
3. Head, Body Lice Are Genetically Very Similar
4. Certain Genetic Regions May Be Tied to Osteoporosis
5. Study of half siblings provides genetic clues to autism
6. Genetic variants, tobacco exposure and lung cancer risk
7. Research Gets Closer to Genetic Roots of Glaucoma
8. Moffitt researcher awarded GE grant to develop tool to detect breast cancer metastasis genetic risks
9. Genetically modified T cell therapy shown to be safe, lasting in decade-long study of HIV patients
10. Some women may be genetically predisposed to smoking-related hot flashes
11. Genetic abnormalities in benign or malignant tissues predict relapse of prostate cancer
Post Your Comments:
(Date:11/30/2015)... ... November 30, 2015 , ... ChiliPad , ... to maximize recovery through quality sleep. Tim DiFrancesco, training coach for the LA ... night’s sleep. ChiliPad precisely regulates the surface temperature of each side of the ...
(Date:11/30/2015)... ... 2015 , ... Using a combination of two blood sugar tests rather than ... to a new study by researchers at the School of Public Health at Georgia ... Combinations of Blood Glucose Tests ,” published in Frontiers in Public Health, the researchers ...
(Date:11/30/2015)... ... November 30, 2015 , ... Newly reviewed and approved “NJ Top Dentist”, ... Tufts School of Dental Medicine in 1935. His father graduated from NYU School ... in dentistry as well as their commitment and passion to the Practice of Dentistry. ...
(Date:11/30/2015)... New York, NY (PRWEB) , ... November 30, 2015 , ... ... New York Times,” will be released on December 1, 2015, to coincide with World ... book about the groundbreaking journalist who covered the AIDS epidemic as he was dying ...
(Date:11/30/2015)... ... November 30, 2015 , ... The American Society for Clinical ... of World AIDS Day 2015. On Nov. 30, ASCP shared its “Give a minute. ... World AIDS Day and the importance of getting tested for HIV. , ASCP has ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... , Nov. 30, 2015   Royal Philips ... the launch of Radiology Solutions, a fully integrated, ... Solutions comprises customized, data-driven practice management approaches that ... help radiology practices improve care delivery and reduce ... Radiological Society of North America Annual Meeting (RSNA) ...
(Date:11/30/2015)... , Nov. 30, 2015  IBA Molecular North ... and distribution of radiopharmaceuticals, announced that as of January ... Inc. (Zevacor Pharma). The decision to rebrand the company ... firm as well as its close relationship with Zevacor ... Illinois Health and Science (IHS). Peter ...
(Date:11/30/2015)... BOCA RATON, Fla. , Nov. 30, 2015 ... Public Research (the Institute) announced today that it ... a medical device start-up company with technology developed at ... based on publicly-funded research, and bridges early funding gaps ... -based universities and research institutions. ...
Breaking Medicine Technology: