IS Breast Cancer Gene Linked to Obesity and Diabetes?

DNA genes

What You Need To Know: The gene known to be associated with breast cancer susceptibility, BRCA 1, plays a critical role in the normal metabolic function of skeletal muscle, according to a new study. Mutations in the BRCA1 gene may also put people at increased risk for metabolic diseases like obesity and type 2 diabetes, this research indicates.

Background: The gene known to be associated with breast cancer susceptibility, BRCA 1, plays a critical role in the normal metabolic function of skeletal muscle, according to a new study led by University of Maryland School of Public Health researchers. Dr. Espen Spangenburg, associate professor of kinesiology, and his laboratory team are the first to identify that the BRCA1 protein is expressed in the skeletal muscle of both mice and humans, and that it plays a key role in fat storage, insulin response and mitochondrial function in skeletal muscle cells.

“Our findings suggest that certain mutations in the BRCA1 gene may put people at increased risk for metabolic diseases like obesity and type 2 diabetes,” said Dr. Spangenburg. “Without BRCA1, muscle cells store excess fat and start to look diabetic. We believe that the significance of the BRCA1 gene goes well beyond breast cancer risk.”

The Evidence: Dr. Spangenburg and colleagues, including researchers from the University of Maryland School of Medicine, Brigham Young University, Karolinska Institutet in Sweden, and East Carolina University, found that the BRCA1 protein exists in both mouse and in human skeletal muscle. This is the first evidence since the discovery of BRCA1 in 1994 that the gene is expressed in human muscle cells.

  • They further established that the protein produced by the BRCA 1 gene binds with a protein known to play an important role in the metabolism of fat in muscle cells known as Acetyl-CoA carboxylase or ACC. After a period of exercise, the BRCA 1 protein binds to ACC, which helps “turns it off.” This deactivation of ACC encourages the utilization of fatty acids by the muscle.
  • Once they established that the two proteins complex together, they sought to answer if BRCA1 plays a critical role in regulating muscle metabolic function. To do so, they “knocked out” the gene so that it was no longer being expressed in the muscle cells cultured from healthy, active and lean female subjects. This was done using shRNA technology specific for BRCA1 in human myotubes (skeletal muscle fiber cells).

The result was that the muscle cells started to look diseased. The removal of BRCA1 from the cells, which simulated what could happen in the cells of a person with a BRCA1 mutation, resulted in increased lipid storage, decreased insulin signaling, reduced mitochondrial function and increased oxidative stress. These are all key risk factors for the development of metabolic diseases, such as obesity, type 2 diabetes and cardiovascular disease.

“Our findings make it clear that BRCA1 plays a protective role against the development of metabolic disease,” Dr. Spangenburg explains. “This gene needs to be there, and should be considered a target to consider in the treatment of type 2 diabetes and/or obesity.”

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

References:

1. K. C. Jackson, E.-K. Gidlund, J. Norrbom, A. P. Valencia, D. M. Thomson, R. A. Schuh, P. D. Neufer, E. E. Spangenburg. BRCA1 is a Novel Regulator of Metabolic Function in Skeletal Muscle.. The Journal of Lipid Research, 2014; DOI: 10.1194/jlr.M043851;

2. University of Maryland. “Breast cancer gene could play critical role in obesity, diabetes.” ScienceDaily. ScienceDaily, 12 March 2014. <www.sciencedaily.com/releases/2014/03/140312114836.htm>.

Breast MRIs On the Rise, Despite Lack of Indicators

MRI breast cancer

Background: The guidelines of the American Cancer Society and the National Comprehensive Cancer Network (NCCN) advise considering breast MRIs if a woman’s lifetime risk of breast cancer is greater than 20 percent. In the general USA population, the population lifetime risk is 12%. Women at high risk include those with the genetic mutations BRCA1 and BRCA2, those who had chest radiation during childhood, or those with a first-degree relative known to have the BRCA1 or BRCA2 mutation. For huh-risk women, annual MRIs and mammograms are recommended.

MRI uses a strong magnetic field and radio waves (not X-rays or radiation) to produce a detailed image. A contrast material is injected into a vein to show tissue details. The scan in the USA is expensive: Mediaid reimbursement is $880 to $1600USD for MRRIs of both breasts, and about $300 for a digital mammogram. Fees for women not on this government program vary widely. While MRIs are more sensitive in finding cancers than are mammograms, false positive results are much more likely, and can lead to unnessary testing (including biopsies) and anxiety.

The journal JAMA Internal Medicine recently reported two studies regarding the use of MRI for imaging the breast. The first reported that:

The use of breast MRIs has nearly tripled in recent years, but the women who could benefit the most are not always getting the expensive imaging test.

The researchers observed that more women at high risk are undergoing screening, which suggests that MRI is being used more appropriately. On the other hand, a second study reported that:

Breast MRIs between 2000 and 2011 jumped 20-fold, then declined and stabilized by 2011. But less than half of women with documented genetic mutations that raise the risk of  breast cancer got the tests. The majority of women who underwent screening with breast MRI did not meet the recommended criteria for appropriate use, whereas many who did meet the criteria did not undergo screening MRI.

My Take: Fortunately, the US Preventative Task Force (USPSTF) has started updating its recommendations on screening for breast cancer. The USPSTF created a research panel that will frame the scope, conduct, and content of a systematic evidence review. A draft of the Research Plan should be posted for public comment until 11 December 2013. Hopefully, we will get better guidance (and perhaps more importantly adherence to said guidance). We have got to do a better job of targeting breast MRI to those who will truly benefit from it. It is unacceptable to find that of women who got breast MRI for screening, only 21 percent met the American Cancer Society criteria for such screening. While today’s post addresses breast MRI as a screening tool (for those without breast cancer), we need to be more selective in the use of breast MRI for those who already have breast cancer.  I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

HealthDay: News for Better Living, 18 Nov 2013; JAMA Internal Medicine 18 Nov 2013.

Contralateral Breast Cancer Risk in Patients With BRCA Mutations: Tamoxifen Reduces Risk

English: Tamoxifen_Structural_Formulae
Tamoxifen (Photo credit: Wikipedia)

Bottom Line: Women with BRCA1 or BRCA2 mutations who underwent adjuvant tamoxifen for breast cancer have a reduced risk of contralateral (other side) breast cancer.

The Study: Investigators used the International BRCA1 and BRCA2 Carrier Cohort Study, the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer, and the Breast Cancer Family Registry to identify women with primary breast cancer. Of the BRCA1 carriers, 24% received the anti-estrogen agent tamoxifen. Of the BRCA2 carriers, 52% got the drug.

Among women treated with tamoxifen after first breast cancer diagnosis, adjusted hazard ratios were 0.38 for BRCA1 mutation carriers and 0.33 for BRCA2 carriers; in other words, women on tamoxifen had a nearly 2/3 reduction in the risk of getting a cancer in the other breast. Still, among BRCA1 mutation carriers that were premenopausal. the risk reduction associated with tamoxifen appeared less apparent for those who had had their ovaries removed (HR 0.70 vs 0.26).

My Take: If you have a BRCA mutation, you should review your cancer risk management with a specialist, including whether you should consider taking tamoxifen as a risk-reducing agent. For those who take tamoxifen as a part of treatment for breast cancer, we now know that you reduce the risk of cancer developing in the other breast, even if you carry a BRCA mutation.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minuteable now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Phillips KA. J Clin Oncol 2013;doi:10/1200/JCO/2012.47.8313.

What are BRCA mutations?

Image

Angelina Jolie has put personalized medicine in the spotlight. Her mother died at age 56 following a 10 year battle with cancer. Jolie recently published a powerful New York Times op ed piece revealing her personal journey after testing positive for a BRCA mutation and her subsequent decision to have risk-reducing removal of her breasts and ovaries. In today’s blog, we turn to the basics of BRCA mutations. What are they, and what are the risks they pose?

BRCA stands for BReast CAncer susceptibility gene. We have BRCA1 and BRCA2, initially discovered by Dr. Claire King at the University of Washington, Seattle. You and I have BRCA genes; in fact we all do. They are tumor suppressor genes that help to keep your cells’ genetic material stable and to prevent cells from growing uncontrollably.

Among women, BRCA mutations (changes) have been associated with a marked increase in the risk of breast and ovarian cancer, often at an early age. On average, the risk of breast cancer increases from 12% (for the average woman in the USA) to about 60% or more among those with a BRCA mutation. The lifetime risk for ovarian cancer increases too, from about 1.4% in the general population to as much as 40%.

Unfortunately, there is more. BRCA1 mutations also increase the risk of cervix, uterus, colon, and pancreas cancer. And BRCA2 mutations also increase the risk of stomach, gallbladder, pancreas, and bile duct tumors as well as melanoma. Among men, BRCA mutations can increase the risk of male breast cancer, with BRCA1 mutations also associated with a higher risk of testicular cancer, and BRCA2 mutations increasing the risk for prostate cancer.

Genetic counseling can be remarkably informative. We will discuss who should consider BRCA testing in a future blog. Thank you. I’m Dr. Michael Hunter.

The small print: Anything stated here is for general use only, and should not be construed as medical advice for an individual. Please check with your health care provider with any questions or concerns.

Gene flaws linked to black women’s greater breast cancer risk

African American young woman

We have long known that African-American women who have breast cancer have a higher risk of death from the disease. Now, we have learned that gene flaws that raise the risk of breast cancer are surprisingly common among blacks who have the disease. A study reported today found that roughly 1 in 5 of these women have BRCA mutations, a problem we typically associate with women of Eastern European Jewish descent. These findings may help to explain why black women have higher rates of breast cancer at young ages, in addition to a higher risk of breast cancer-related death. Dr. Jane Churpek, the study leader, was very surprised by the results.

The study included 249 black breast cancer patients from the Chicago area. Many had breast cancer at a young age, and half had a family history of the disease. Here’s where the investigators went beyond the usual genetic testing: All patients had complete gene sequencing for all 18 known breast cancer risk genes rather than the usual tests that simply try to find a few specific mutations in BRCA genes. The results? Gene flaws were found in 56, or 22% of study participants; 46 involved BRCA1 or BRCA2, and the rest were less commonly mutated genes. Among black women with “triple negative” (estrogen receptor negative, progesterone receptor negative, HER2 negative), or the worst subtype of breast cancer, 30% had harmful mutations.

To me, the results point to the fact that too few African-American women have been included in genetic studies in the past. We really had no clue about the extent of mutations among this population. And if a parent has a BRCA mutation, children have a 50% chance of getting the gene. Today, we have more knowledge about the specifics of the gene problem among African American women with breast cancer. I’m Dr. Michael Hunter.