High Cholesterol May Fuel Growth, Spread of Breast Cancer (In Mouse Models)

Spacefill model of the Cholesterol molecule
Spacefill model of the Cholesterol molecule (Photo credit: Wikipedia)

A byproduct of cholesterol functions like the hormone estrogen to fuel the growth and spread of the most common types of breast cancers, researchers at the Duke Cancer Institute report. The researchers also found that anti-cholesterol drugs such as statins appear to diminish the effect of this estrogen-like molecule.

Published in the Nov. 29, 2013, edition of the journal Science, the findings are early, using mouse models and tumor cells. But the research for the first time explains the link between high cholesterol and breast cancer, especially in post-menopausal women, and suggests that dietary changes or therapies to reduce cholesterol may also offer a simple, accessible way to reduce breast cancer risk.

“A lot of studies have shown a connection between obesity and breast cancer, and specifically that elevated cholesterol is associated with breast cancer risk, but no mechanism has been identified,” said senior author Donald McDonnell, Ph.D., chair of the Department of Pharmacology and Cancer Biology at Duke. “What we have now found is a molecule — not cholesterol itself, but an abundant metabolite of cholesterol — called 27HC that mimics the hormone estrogen and can independently drive the growth of breast cancer.”

The hormone estrogen feeds an estimated 75 percent of all breast cancers. In a key earlier finding from McDonnell’s lab, researchers determined that 27-hydroxycholesterol — or 27HC — behaved similarly to estrogen in animals.

For their current work, the researchers set out to determine whether this estrogen activity was sufficient on its own to promote breast cancer growth and metastasis, and whether controlling it would have a converse effect.

Using mouse models that are highly predictive of what occurs in humans, McDonnell and colleagues demonstrated the direct involvement of 27HC in breast tumor growth, as well as the aggressiveness of the cancer to spread to other organs. They also noted that the activity of this cholesterol metabolite was inhibited when the animals were treated with antiestrogens or when supplementation of 27HC was stopped.

The studies were substantiated using human breast cancer tissue. An additional finding in the human tissue showed a direct correlation between the aggressiveness of the tumor and an abundance of the enzyme that makes the 27HC molecule. They also noted that 27HC could be made in other places in the body and transported to the tumor.

“The worse the tumors, the more they have of the enzyme,” said lead author Erik Nelson, Ph.D., a post-doctoral associate at Duke. Nelson said gene expression studies revealed a potential association between 27HC exposure and the development of resistance to the antiestrogen tamoxifen. Their data also highlights how increased 27HC may reduce the effectiveness of aromatase inhibitors, which are among the most commonly used breast cancer therapeutics.

“This is a very significant finding,” McDonnell said. “Human breast tumors, because they express this enzyme to make 27HC, are making an estrogen-like molecule that can promote the growth of the tumor. In essence, the tumors have developed a mechanism to use a different source of fuel.”

McDonnell said the findings suggest there may be a simple way to reduce the risk of breast cancer by keeping cholesterol in check, either with statins or a healthy diet. Additionally, for women who have breast cancer and high cholesterol, taking statins may delay or prevent resistance to endocrine therapies such as tamoxifen or aromatase inhibitors.

The next steps for research include clinical studies to verify those potential outcomes, as well as studies to determine if 27HC plays a role in other cancers, McDonnell said.

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.

Reference: Duke University Medical Center (2013, November 28). High cholesterol fuels growth, spread of breast cancer. ScienceDaily. Retrieved November 28, 2013, from http://www.sciencedaily.com­/releases/2013/11/131128141357.htm

Allergies and Hematologic Cancer Risk: Is There a Link?

young white woman blowing nose allergy

Women with airborne allergies could be at higher risk for hematologic malignancies than women without allergies, researchers contend.

The Study: Data from a prospective cohort study of more than 66000 older adults in Washington state (USA) found that women with any airborne allergen had a 1.47x increase in risk for a hematologic cancer. In addition, women who hit the allergy trifecta of sensitivity to plants, grass, and trees had a 73% greater chance of developing a mature B-cell lymphoma or related disorder.

Overall, men were more likely than women to develop a hematologic malignancy, but the risk in men was not significantly associated with allergic status, write Mazyar Shadman, MD, MPH, and colleagues from the Fred Hutchinson Cancer Research Center in Seattle.

“For other cancers, the idea long ago was that if you have allergies, your immune system is kind of hyperactive, and that should lower your risk for other cancers,” he explained. However, he added, “for hematologic cancers, you could go either way, because immune surveillance would be good but, if you have allergies, that means that cells are dividing more to mount the immune response, increasing the chance of mutations,” offers Richard G. Stevens, PhD, professor of cancer epidemiology at the University of Connecticut Health Center.

My Take: While allergies may increase the risk of cancer of the blood/lymph system, it may lower the risk of other cancers, including of the head and neck. Although the study was large and had comprehensive baseline data, it was limited by its reliance on self-reporting of allergies and by the inclusion of data only on current allergies, rather than allergic history. 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.

Reference: Am J Hematol. 2013;88:1050-1054. Abstract

Cinnamon May Reduce Your Blood Sugar, But How?

cinnamon

Glucose is the simple sugar that circulates in the blood. Our cells rely on it for energy, so glucose needs a way to get from the bloodstream into cells. Insulin is a hormone that also circulates in the blood. When insulin attaches to insulin receptors on the outside of cells , it’s as if doors to the cells swing open and glucose is allowed in. In people with type 2 diabetes, cells resist this effect of insulin, so glucose doesn’t get into cells and builds up in the blood instead.

Cinnamon contains several chemicals that stimulate insulin receptors so glucose can get into cells and that means levels in the blood go down. There’s some debate about exactly which chemicals are the critical ones. While the evidence for a cinnamon benefit on blood sugar is suggestive, it is not sufficiently high level to allow us to advocate substituting it for conventional medicine. Still, exercise, maintenance of a body mass index of 20 to 25, and a bit of cinnamon are all reasonable. 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.

Prostate Cancer, Obesity, and Smoking

stop cancer

Men who are overweight have a higher risk of the lethal form of prostate cancer. And for those who are bees, the risk is even higher.

The Research: A meta-analysis (a study combining several studies) examined 1.2 million initially cancer-free men. While being overweight did not increase the risk of prostate cancer overall (including quiet/indolent type and the more lethal forms), it did increase the risk of the lethal prostate cancer. The same observation is true of smoking: While it does not increase the overall risk of prostate cancer, it does increase the risk of the potentially lethal form.

My Take: Being overweight may increase the chances of prostate cancer spread via boosting of inflammation and raising levels of growth factors. Some of the factors that drive cancer metastasis (spread to distant sites) appear to be different than than those that cause prostate cancer. Keep moving (aim for a minimum of 150 minutes per week of the equivalent of a brisk walk), and don’t smoke! 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.

Reference: Cancer Prev Res 4:486;2011.

Prostate Cancer: Can You Reduce Risk Through Exercise?

English: Micrograph showing prostatic acinar a...
Micrograph showing prostatic acinar adenocarcinoma (the most common form of prostate cancer) Gleason pattern 4. H&E stain. Prostate currettings. (Photo credit: Wikipedia)

An increasing body of evidence points to exercise as a strong means to reduce the risk of prostate cancer. This holds true for the incidence of lethal prostate cancer (as opposed to the more quite/indolent type) and for decreasing the progression of the disease for those who have it. The effect is not small.

The Research: Stamfer and others tracked roughly 2700 men with prostate cancer for four years. Those who reported at least three hours a week of vigorous activity had a 61 percent lower risk of dying of prostate cancer than those who got less than an hour a week.

We saw a strong association with a lower risk of lethal disease, observed the author, Meir Stampfer (Harvard School of Public Health).

Still, with exercise, one wonders whether inactivity causes men to die or whether illness causes men to be inactive. So researchers looked 1455 men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) study. The study looked at men who have been diagnosed with – and in most cases, treated for – prostate cancer to see whose cancer is more likely to progress (manifest as a rise in PSA and/or spread to distant sites such as the bones).

Among men in CapSURE, those who walked briskly for t least three hours a week had a 57 percent lower rate of progression than those who walked at an easy pace for less than three house a week. Very few men in the study reported more vigorous exercise such as running or biking. I’m Dr. Michael Hunter, and you know what you need to do!

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.

Reference: J Clin Oncol 29;726:2011; Cancer Res 71:3889, 2011.

Triple-Negative Breast Cancer: Risk Factors

breast cancer in female body diagram

Breast cancer growth may be driven by the so-called female hormones, estrogen and progesterone, or by HER2. But some breast cancers are not driven by any of these; the ER/PR/HER2 negative cancers are sometimes referred to as “triple negative,” and represent among the most aggressive breast cancers. So why do these cancers occur? What are the risk factors for triple negative breast cancer?

Two of the largest studies to date look at triple-negative breast cancer, and have found some reproductive factors (pregnancy and multiple childbirth), obesity, and lack of physical activity to increase risk.

The Research: Both studies used data from more than 155000 women enrolled in the Women’s Health Initiative. Of the group, 307 developed triple-negative breast cancer after a follow-up of 8 years, and 2610 were found to have estrogen-receptor-positive (ER+) breast cancer.  Let’s look at each of these studies:

  1. In the first study, investigators found that obese women had a 35% higher risk (they were 1.35x more likely) for triple-negative breast cancer, as compared to women with the lowest body mass index (BMI).
  2. In the second study, the number of births affected risk for triple negative breast cancer: Women who had given birth to 3 or more children were at higher risk than women who had given birth to one child (hazard ratio 1.46).

My Take: Triple negative breast cancer appears to be a very different disease, compared to the other breast caner subtypes. While the hormonal changes of pregnancy makes the breast less susceptible to ER-positive breasy cancer, these mechanisms do not reduce the risk for triple-negative disease. The link between pregnancy and increased risk for triple-negative breast cancer may be due to an abnormal response of the breast to pregnancy. Obesity and physical inactivity, on the other hand, might increase risk bu affecting insulin-like growth factors or inflammatory changes in the breast. 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.

Reference: Cancer Epidemiol Biomarkers Prev. Published online March 1, 2011. Abstract; J Natl Cancer Inst. Published online February 23, 2011. Abstract; Medscape Medical News, 2011 WbeMD LLC.