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An international team of researchers has shown how mutations in the BRCA1 gene lead to breast cancer. Findings show that one way BRCA1 mutations cause cancer is by knocking out a powerful tumor suppressor gene known as PTEN.

“These findings are exciting because ever since the link was established between BRCA1 and breast cancer more than 10 years ago, we have been frustrated by our lack of understanding about how mutations in this gene cause breast cancer. We have been stymied by our limited resources to treat these cancers, which are associated with very poor prognoses. Now that we know that PTEN is involved, we finally have a target for therapy for these cancers,” said Dr. Parsons, the study’s corresponding author. Dr. Parsons is director of the Avon Foundation Breast Cancer Research Laboratory and director of the Breast Cancer Program of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital.

In 1997, Dr. Parsons led one of the two teams that independently discovered the PTEN, one of the most important tumor suppressor genes altered in breast cancer, as well as in brain and prostate cancers. PTEN is now recognized to be mutated in about 30 percent of all cancers, making it the second most mutated gene in cancer after p53. Knocking out PTEN sends a strong pro-growth signal on tumor cells. This is unlike the BRCA1 mutation, which only predisposes the cells to accumulate genetic damage and sends an indirect signal for cell growth. “Once a cell loses PTEN, it has a growth advantage over its neighbors and starts on the road to cancer,” said Dr. Parsons.

PTEN mutations promote runaway tumor cell growth by increasing the activity of a series of different proteins in the cell known as the PTEN/PI3K pathway. Shutting down any one of those proteins could potentially stop growth of the cancer. Investigational therapies to shut down proteins in the PTEN pathway are currently in Phase I clinical trials.

How the BRCA1 Mutation Mechanism Was Pinpointed

Dr. Parsons and his research team made the connection between BRCA1 and PTEN using techniques to search for physical chromosome breaks within the PTEN gene—a technique that had never before been used. Previous searches for PTEN mutations in BRCA1 tumors had looked for conventional mutations and failed to turn up any abnormalities.

The researchers scanned 34 biopsies taken from women with BRCA1 tumors. The PTEN gene had been split in two, but inadequately repaired in about one-third of the cancers. In some cases, entire sections of the gene were missing; in others, one-half of the gene was reattached to other regions on the chromosome.

These types of large chromosomal mistakes stem directly from the tumor’s lack of BRCA1, a gene that is normally involved in the repair of such damage. In breast cancers from women with normal BRCA1, such large mutations in PTEN were rarely detected.

Finding May Affect 50% of BRCA1 Breast Cancers & Lead to New Treatments

Dr. Parsons estimates that about 50 percent of BRCA1 breast cancers will be found to harbor mutated PTEN once a complete analysis of chromosomal mutations is done.

Breast cancer tumors caused by BRCA1 are known as basal-like or triple-negative because these tumors usually lack estrogen, progesterone, and HER2 receptors, which are needed for most breast cancer treatments to be effective. Basal-like breast tumors are found in 10 to 20 percent of women with non-hereditary breast cancer (meaning, not caused by a genetic mutation in BRCA1 or another gene), and the researchers found that PTEN is also lost in the majority of these breast tumors as well.

“Our results point to PTEN as a major player in both hereditary and non-hereditary basal-like breast cancer, a finding that may now be exploited to develop new therapeutic strategies to improve outcomes for women with these aggressive tumors,” said Dr. Saal, who at the time of the research, was a fellow in Dr. Parsons’ Avon Foundation Breast Cancer Research Laboratory.

The researchers also predict that other cancer genes besides PTEN are targeted by BRCA1.

“By using the same techniques we used to find gross chromosomal rearrangements in PTEN, we hope to start identifying additional mutated genes involved in the development of breast cancer,” said Dr. Parsons.

“These kinds of mutations that break tumor suppressors in half may turn out to be common in many kinds of carcinomas, particularly those with deficiencies in DNA repair pathways similar to BRCA1, a question that only a systematic search can answer,” said Dr. Saal.

“Similar research is underway in tumors from carriers of germline mutations in BRCA2, the other known major breast cancer susceptibility gene,” said Dr. Borg. “BRCA2 has a role downstream in the same DNA double strand break repair pathway as BRCA1, but tumors from BRCA2 mutation carriers have a quite different phenotype compared to BRCA1 tumors, less often involving PTEN loss. However, like BRCA1, BRCA2 tumors have an instable genome with massive chromosomal aberrations, suggesting that other genes may be targeted.”

Breast Cancers Caused by BRCA1 Mutations are Especially Lethal & Difficult to Treat

Basal-like breast cancer tumors, whether caused by BRCA1 mutations or of the non-hereditary type, are among the most aggressive tumors—they grow fast and spread quickly, making them more likely than other types of cancer to be fatal. These tumors are more likely to be resistant to standard breast cancer treatments, such as Tamoxifen or Herceptin, making them especially difficult to treat. As a result, many young BRCA1 carriers opt to have their breasts prophylactically removed instead of waiting for cancer to appear.

Breast cancers caused by BRCA1 mutations tend to affect women much earlier—often before menopause and sometimes in their 20s and 30s—and between 60 and 80 percent of women who carry a BRCA1 mutation will develop breast cancer at some point during their lives. BRCA1 mutation carriers are most common among African-American women and women of Ashkenazi Jewish descent. Inherited BRCA1 (and BRCA2) mutations also predispose women to ovarian cancer, a disease that frequently escape early diagnosis and which has a fatal outcome in advanced stages.

The study will be published in the January, 2008 issue of Nature Genetics. The study was led by Ramon Parsons, M.D., Ph.D., the Avon Foundation Professor of Medicine and Pathology at Columbia University College of Physicians and Surgeons and Åke Borg, Ph.D., professor of oncology at Lund University. The paper’s first author was Lao Saal, Ph.D.

The research was supported, in part, by the Avon Foundation, the OctoberWoman Foundation, and the National Cancer Institute and the Swedish Cancer Society.

Source: Columbia University Medical Center

Most underarm antiperspirants contain as the active ingredient, Aluminium Chlorohydrate, as you will probably remember there has been controversy about Aluminium, since the 1950’s when it was a popular metal used for making cooking pots, Saucepans and Fry Pans and that it could be one of the contributing factors to Alzheimer’s, now we have another problem that could also be related to Aluminium, Breast Cancer.

Research shows that one of the leading causes of Breast Cancer could be the use of antiperspirants. The human body has a number of areas, that it uses to purge Toxins from the body, these are, behind the knees, behind the ears, the groin area, and the armpits. The toxins are purged from the body in the form of perspiration and antiperspirant as the name clearly suggests prevents you from perspiring, thereby inhibiting the body from purging Toxins from the armpit area.

These Toxins do not just disappear, Instead, the body deposits them in the Lymph Nodes below the arms, since it is unable to sweat them out. A concentration of Toxins then builds up in the areas such as the armpits, which can then lead to cell mutations, which is cancer.

It cannot be ignored, that nearly all Breast Cancer Tumors occur in the upper outer quadrant of the breast area, this is where the Lymph Nodes are located. Men are less likely (but not totally exempt) to develop breast cancer prompted by the use of antiperspirants, because the antiperspirant is more likely to be caught in the armpit hair, rather than directly applied to the skin, but ladies, who shave their armpits, increase the risk by causing imperceptable nicks in the skin, which allow the chemicals to enter easily into the body through the armpits.

This article is aimed mainly at ladies, but please be aware that there are a few antiperspirants on the market that are made from natural products, but basically they would still trap the Toxins in the same areas. The best solution is to use deodorants, rather than antiperspirants, also please remember that the Eight Essential Sugars in Glyconutrients can also help to fight off Toxins. Please view the benefits that Glyconutrients can give you, Check our Web Sites.

Article Source: Health Guidance

Drug Fights Cancer And Tumors

Nov. 29 - When breast cancer spreads to other parts of the body, it can be deadly. But now a new drug that seems to be able to stop advanced breast cancer from progressing and even reduces the size of tumors.

About 10 years ago, Karen Pike got the news. The mother of two had breast cancer.

Karen Pike, Breast cancer survivor: “I don’t have any history in my family, so at 37, it was pretty scary. Our kids are 5 and 7, and I just went numb.”

Karen’s faith - and family - helped her stay strong. She needed the strength when the cancer came back three more times.

Karen Pike: “I couldn’t have done any of this without my family. I know that I couldn’t.”

Karen has also relied on a team of doctors - and is now part of a clinical trial on a drug called sutent. In a study, the pill shrank tumors by one-third or more in 15 percent of patients - significant because they had very advanced disease and didn’t have any luck with other treatments.

Doctor George Sledge says Sutent could be used as a frontline treatment for breast cancer that has spread.

George Sledge, M.D., Oncologist: “This holds out so much promise that I think if you are a physician dealing with breast cancer research you can only be excited about this.”

Karen’s only been on the drug for a month, but the lump in her neck has already drastically gone down in size - keeping her optimistic for the future.

Karen Pike: “Seeing both of my kids graduate from college, get married, have children, live a long life and be healthy for the rest of my life.”

A simple dream she hopes will come true.

Sutent is an interesting drug. It has also shown promise in treating gastrointestinal and kidney tumors when other treatments start to fail. Right now, right now, it’s just under investigation but could become FDA approved for certain cancers in the next year.

Researchers say, this drug is part of an entirely new class of agents and is working through mechanisms that haven’t been used before.

By :ABC7

Breast screening may produce false positives

Concerns have been raised that breast cancer screening might lead to some women undergoing unnecessary treatment.

Researchers looked at international studies on half a million women.

They found that for every 2,000 women screened over a decade, one will have her life prolonged, but 10 will have to undergo unnecessary treatment.

UK experts said women over 50 should go for their breast checks, but a screening pioneer raised doubts about the NHS programme’s future.

The report, published in the Cochrane Library, involved a review of breast cancer research papers from around the world.

Women invited to screening should be fully informed of both benefits and harm Dr Peter Gotzsche, researcher

The scientists found mammograms did reduce the number of women dying from the disease.

But they also discovered it was diagnosing woman with breast cancer who would have survived without treatment, meaning they were undergoing unnecessary chemotherapy, radiotherapy or mastectomies.

About a fifth of cancers picked up by screening are in the milk ducts of the breast.

Some of these cancers will progress while others will not - but there is no way of predicting what will happen.

This means women and doctors have to decide whether or not to risk doing nothing, or go ahead with treatment which might be unnecessary.

They also revealed a further 200 women out of every 2,000 experienced distress and anxiety because of false positives - a result that indicated a cancer was present but was later found to be wrong.

Lead researcher Dr Peter Gotzsche, of the Nordic Cochrane Centre, said: “Women invited to screening should be fully informed of both benefits and harm.

“When screening advocates and their organisations produce information materials, they generally emphasise the benefits and omit information on the major harms.

“This needs to be corrected to ensure that women can give genuinely informed consent before joining a screening programme.”

In 2001, the same authors concluded there was no convincing evidence that screening programmes reduce mortality from the disease.

NICE referral?

Michael Baum, professor of surgery at University College London who set up one of England’s first screening programme in 1987, told the Daily Telegraph: “This latest evidence shifts the balance even further towards harm and away from benefits.

The benefits of breast screening far outweigh the risks Julietta Patnick, director of the NHS Cancer Screening Programmes

“If this report stands up, the NHS screening programme should be referred to the National Institute for health and Clinical Excellence to decide whether it should be closed down.”

But a spokesman for the Department of Health said that, as mammography was an accepted, evidence-based technology, it would not be appropriate to refer the screening programme to NICE.”

And Professor John Toy, medical director of Cancer Research UK, said: “Researchers in the field all agree that breast screening saves lives although they differ in their views about the balance of the pros and cons.

“Benefits need to be balanced against any disadvantages, as is the case with all medical treatments.

“Certainly women invited for screening should be made aware of both potential benefits and downsides - such as possible initial mis-diagnosis.

“But overall we continue to encourage UK women to participate in the NHS Breast Screening Programme.”

Jeremy Hughes, chief executive of Breakthrough Breast Cancer said: “When early changes are picked up by screening it is not currently possible to predict whether or not they will progress and so treatment is usually offered to prevent breast cancer from developing.

“It’s important women are given clear information about their treatment options. Early detection saves lives. Women over 50 should not be discouraged from taking up their screening appointments.”

And Julietta Patnick director of the NHS Cancer Screening Programmes said: “The programme saves 1,400 lives every year. Women who are screened are also less likely to have a mastectomy than those who are not screened.

“For lives to be saved breast screening must detect cancers in the early stages. The benefits of breast screening far outweigh the risks and I would strongly encourage all women to make an informed choice to attend for screening when invited.”

British scientists have identified a new breast cancer susceptibility gene, adding one more piece to the puzzle of the genetic causes of breast cancer.

Women with mutations in a gene called BRIP1 have twice the normal risk of developing breast cancer, according to the study published today in Nature Genetics. Canadian experts say this is an important step in cancer research, but caution that patients won’t soon see direct benefits from the finding.

Over the last decade, scientists have identified a number of breast cancer susceptibility genes, five of which have a role in repairing DNA. Mutations in the BRCA1, BRCA2 and TP53 genes are associated with a high risk of developing the disease, between a 10 to 20-fold increase. Mutations in the CHEK2 and ATM genes are associated with a lower risk, approximately a two-fold increase.

The newly identified gene, BRIP1, is in the same class as CHEK2 and ATM, the British team of researchers report. Study lead author Nazneen Rahman, a researcher with the Institute of Cancer Research, was not available for comment.

The research team looked for the BRIP1 gene in 1,212 women with breast cancer who had a family history of the disease, but who did not have the known breast cancer genes BRCA1 or BRCA2. They also looked for the BRIP1 gene in 2,081 healthy women.

Nine women with breast cancer had the mutation, while only two of the healthy women had it. The team estimated that women who carry a faulty version of BRIP1 have twice the normal risk of developing breast cancer.

There is no doubt that BRIP1 plays a role in breast cancer, but it’s doubtful that it will immediately be used in screening procedures to help prevent the disease, said Steven Narod, director of the Familial Breast Cancer Research Unit at Women’s College Research Institute in Toronto and who is credited with helping discover the BRCA1 and BRCA2 gene mutations.

“A two-fold risk is not trivial, but it’s not the kind of message that will mean women will run out and get tested,” he said.

The baseline risk for a woman developing breast cancer over her lifetime is seven per cent, he explained. Women with either the BRCA1 or BRCA2 mutation have a 70 per cent lifetime risk, while women with the BRIP1 mutation have a 14 per cent lifetime risk, he said.

It’s estimated that 1 in 200 women in Canada carry either the BRCA1 or BRCA2 mutation. Approximately 1 in 1,000 women carry the faulty version of BRIP1, said Narod.

Ellen Warner, a medical oncologist at the cancer centre at the Sunnybrook Health Sciences Centre, said BRIP1 is a rare gene and screening for it won’t provide women with any more information than what can be determined from their family history.

“From a women’s point of view, this is not a breakthrough,” she said. “It will not change the lives of women.”

But the study is exciting news for cancer researchers, she said.

Thousands of people are working to figure out the role genetics play in breast cancer. The breast cancer susceptibility genes that have been identified to date probably only account for 25 per cent of the familial risk of breast cancer, said Warner. There may be hundreds of rare genes associated with an increased risk in breast cancer.