how alcohol consumption increases risk of bc and growth of breast cancer elucidated

[Lani]

New animal study may explain why alcohol consumption increases breast cancer risk [Eureka News Service]
WASHINGTON — For the first time, scientists have used a laboratory mouse model to mimic the development of human alcohol-induced breast cancer. The results are part of a new study, Chronic Alcohol Consumption Increases Tumor Growth and Amgiogenesis of Breast Cancer in Female Mice, conducted by Brandi Busby, Wei Tan, Jordan Covington, Emily Young, and Jian-Wei Gu, all of the University of Mississippi Medical Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS. Dr. Gu will present the team's findings in detail during the American Physiological Society (APS; www.the-APS.org) annual meeting, which is being held as part of the Experimental Biology (EB '07) meeting. More than 12,000 scientists are attending the conference, being held April 28 - May 2, 2007 at the Washington, DC Convention Center.
Background

Alcohol (EtOH) consumption — even moderate — is a well-established risk factor for breast cancer in women. A recent study showed that 60 percent of female breast cancers worldwide were attributable to alcohol consumption. Nevertheless, the mechanisms of alcohol-induced breast cancer are poorly understood.

The definitive biological effects and molecular mechanisms of EtOH on progression and malignancy of breast cancer have not been investigated using a mammalian breast cancer model that mimics the human disease. Scientists have suggested that the possible mechanisms involved include the agitation of estrogen metabolism and response; cell mutation by the EtOH metabolite acetaldehyde; oxidative damage; and one-carbon metabolism pathways through reduced folic acid.

Methodology

To date, there has not been an animal model that faithfully mimics the human disease with respect to characteristics of breast cancer, immunocompetence, and physiologically relevant EtOH intake. The researchers addressed and overcame the obstacles and developed a novel mouse breast cancer model. The model mimics human breast cancer disease in which the estrogen receptor-positive breast adenocarcinoma cells were subcutaneously injected near the pad of the fourth mammary gland of female immunocompetant mice (C57BL/6). The six-week-old female mice were fed with moderate EtOH (one percent in drinking water) for four weeks, the equivalent of two drinks per day in humans. The control mice received regular drinking water only.

In the second week of the experiment, mouse breast cancer cells (5x105 E0771) were injected at cite referenced above. At the end of the experiment, the tumors were isolated to measure tumor size, examine intratumoral microvessel (IM) density via CD 31 immunohistochemistry staining, and assessing VEGF protein levels via ELISA. These steps were taken to determine the effects of EtOH intake in physiologically relevant doses on tumor growth and angiogenesis in mouse breast cancer.

Results

The researchers found:


that moderate alcohol consumption significantly increased the tumor size of breast cancer in mice, which was a 1.96-fold increase in tumor weight vs. control mice;
that alcohol intake caused a 1.28-fold increase in tumor microvessel density vs. the control group;
a significant increase in tissue protein levels of VEGF were found in the tumors of the mice treated with EtOH vs. control group;
EtOH intake did not cause significant changes in the body weight of the mice.
Conclusions

This study presents the first animal model to confirm that alcohol consumption stimulates tumor growth and malignancy of breast cancer, and reveals some of the mechanisms of alcohol-induced breast cancer. The findings demonstrate that even moderate alcohol consumption significantly stimulates tumor growth of breast cancer and that induction of tumor angiogenesis and VEGF expressions are mechanisms which are associated with the progression of this deadly disease.

[R.B.]

Omega 3s may play a part here too.......

Many thanks Lani.


Per a trial/s I have seen on my wanders


Alcohol blocks the pathways by which the body makes DHA EPA as well as the long chain omega sixes (sixes - which I guess is less of a problem on average due to high six intake build up in body etc etc) (I am not sure about very low consumption)

And in the brain at least increase COX 2 etc...

And when take in greater quantity leads in the brain to release of DHA EPA so lower levels of protective PUFAs...........

Women are more susceptible as they have a higher need of EPA DHA etc

RB

[Audrey]

Thanks for posting, Lani--from my reading, though, the study doesn't apply to er- or Her2+ tumors, just er+, right? (I'm not giving up my glass of wine yet!)

[Lani]

Of the several mechanisms they postulate, only one applies to ER+s and most her2+s are associated with increased VEGFR.

I recently cited the only article I have ever found looking at the association of dietary factors and her2+ breast cancer only. Most articles look at environmental or dietary associations either with ALL breast cancers or with ER+ breast cancers or ER- breast cancers.

As her2+ ER- breast cancers make up about 12% of breast cancer and
her2+ER+ breast cancer about 10% of breast cancer, I think you will have to wait a long time before studies looking at the association of alcohol and these subtypes of breast cancer are published.

By the way, all these studies are of limited value as they are retrospective studies (looking back at what people remember or say they remember or did) vs enrolling patients and seeing how the possible risk factor in fact, affected the rate of breast cancer in the group.

Of course, diet is not the ONLY THING different in these groups--they cannot be truly controlled experiments.

[suzan w]

Not that I am promoting drinking...but, I had been sober for 12 years and then diagnosed with bc...go figure!

[Lani]

Last Updated: Tuesday, 1 May 2007, 11:08 GMT 12:08 UK

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Drinking 'fuels growth of tumour'

Alcohol has been linked to cancer before
Drinking just two alcoholic drinks a day when you have breast cancer fuels the growth of tumours, a study says.
It has long-been known alcohol increases the risk of developing cancer but the effect of drinking once cancer is present is less established.

A University of Mississippi team found giving mice the equivalent of two to four drinks a day doubled the normal growth of a tumour after four weeks.

Cancer patients are often just told to moderate drinking.

In the study, researchers gave female mice the human equivalent of two drinks a day for four weeks, while a control group were given no alcohol.


Every day, we produce a lot of cancer cells, but they don't become bigger
Jian-Wei Gu, lead researcher

The mice were then injected with breast cancer cells.

Within four weeks, the tumours in the alcohol-fed mice weighed 1.4g on average, almost twice the size of tumours in the control group.

The team, which presented the research to the American Physiology Society, said alcohol caused cancer cells' blood vessels to grow which in turn fuelled the growth of the tumour.

The mouse study builds on an earlier research with chicks that showed alcohol consumption increased the expression of a protein known as VEGF.

VEGF fuels tumour growth by spurring the development of blood vessels in cancer cells that might otherwise die.

Normally, the immune system can kill off small tumours. However, when they grow large enough the body can no longer fight off the tumour cells.

Tumours

Lead researcher Jian-Wei Gu said: "The vast majority of tumours result from over expressed VEGF.

"Every day, we produce a lot of cancer cells, but they don't become bigger.

"But if the cells establish blood vessels, the tumour grows and strengthens, a process known as angiogenesis."

And he added he would advise patients not to drink if they were undergoing cancer treatment.

"I don't think two to four drinks per day is okay.

"The public needs to know of these results."

Ed Yong, Cancer Research UK's science information officer, said: "The link between alcohol and breast cancer, and many other cancers for that matter, is well known.

"But this is the first time I have heard of the impact of alcohol once cancer is there."

He said more research was needed to see if the findings were replicated in adults and whether it also applied to other cancers.

[pattyz]

Suzan,

I'm with you. Sober for 20 yrs at first dx age 50. Mom and her mom not so with their own dx..... But. I refuse to get dragged into the 'blame game'. Just REFUSE. It serves no purpose.

hugs,
patty

[AlaskaAngel]

I know I am a very simple person looking for very simple answers, but the scientific analysis involved amazes me.

Alcohol is a sugar, isn't it?

Why is there no mention of the mere possibility in the discussion that alcohol is fueling angiogenesis because it is a sugar?

Baffled,

AlaskaAngel

[Hopeful]

AlaskaAngel,

Sugar is converted into alcohol via the process of fermentation, via the action of an organism (yeast) that gobbles up the sugar and "burps" out carbon dioxide. The intriguing thing (to me, anyway) is that this conversion is an anerobic process (without oxygen), and cancer thrives under anerobic conditions. The effect of sugar on bc may be more similar to the effect of alcohol, rather than the other way around (the old "chicken and egg" conundrum).

Hopeful

[StephN]

Hi Alaska -Your comment on alcohol breaking down to a sugar was exactly why I cut to the bone on the other sugars (as in simple sugars) in my post cancer dx diet. I WANTED to have my glass of wine with dinner!

Regarding the science mentioned in Lani's posts, VEGF is the biggie that gets the cancer moving. Perhaps we need to find out more about what COMPONENT of the alcohol activates the VEGF. AS WELL as what OTHER bits in our blood could activate it.

I am also wondering what FORM the alcohol was that was given to the mice. I only drink wine and the very occasional beer. These drinks are much lower in alcohol content than say a Kamakaze.

I don't see a simple answer on this one!!

[AlaskaAngel]

I think there is a hidden connection too, Steph. One can avoid eating or drinking certain things day by day or even minimize certain things on the whole, but for the long haul it is quite difficult. I don't just mean white sugar. I grew up on a home truck garden and love fresh fruit, and yet the sugar content there has to be considered too...

AlaskaAngel