MONDAY, Dec. 10 (HealthDay News) -- Scientists believe they've discovered how mutations in the cancer-susceptibility gene called BRCA1 can cause some breast cancers.

Basal-like breast cancers (BBCs) represent 10 percent to 20 percent of all breast cancers. BBCs generally have a poor prognosis, are difficult to treat, and are almost always associated with hereditary mutations in the BRCA1 gene, the researchers said.

The researchers found that inherited mutations in the BRCA1 gene deactivate another gene known as PTEN, which helps to suppress tumors. This suppressor gene is deactivated by the mutated BRCA1 gene's failure to repair a break in the PTEN gene's DNA, the scientists said.

The loss of the PTEN gene's tumor-suppressing ability allows increased cell activity that increases tumor growth. That action "can convert the cell from being a well-behaving entity to a bad citizen," said study co-author Dr. Ramon Parsons, a professor of medicine and pathology at Columbia University's College of Physicians and Surgeons.

"This is a very important finding, because this type of breast cancer doesn't have a type of therapy targeted at this point," Parsons said. Basal-like or triple negative tumors don't have receptors for the hormones estrogen and progesterone or the protein HER2, which most breast cancer therapies target, he said. Drugs that can target the pathway related to mutated PTEN genes "may be a way we can improve the survival for women with these basal-like tumors," he added.

Parsons said several pharmaceutical companies already are developing drugs to do just that.

"My guess is there's going to be a huge bolus of clinical trials with these drugs in the next couple of years," he said. "Since there's going to be such a large variety of compounds, my hunch is one or more will be effective." By effective, Parson said he doesn't mean one of them will offer a cure, but the drugs in the right combination could lead to a cure.

The development of these drugs also may be important for other types of cancers that can involve deactivating the PTEN gene, Parsons said.

The study results were published online Dec. 9 in the journal Nature Genetics.

Parsons said the discovery of the PTEN deactivation "was kind of a real long-term detective story." For 10 years, researchers have been trying to understand how the mutation in the BRCA1 gene can cause breast cancer. Instead of using traditional gene-sequencing techniques, Parsons and his colleagues looked for physical breaks in the PTEN gene. "PTEN is actually physically broken in half, we estimate, in 30 to more than 50 percent of the BRCA1 tumors," he said.

Dr. Jeffrey Weitzel, an associate professor of medical oncology at the City of Hope Comprehensive Cancer Center in Duarte, Calif., said the study by Parsons' team "helps us understand what's under-appreciated in the complex nature of tumor changes."

Andrew Godwin, director of the clinical molecular genetics laboratory at the Fox Chase Cancer Center in Philadelphia, added: "As we move towards personalized health care [and] medicine, identifying the cadre of genetic defects in a given breast tumor will likely influence how that patient is ultimately treated."

More information

For more on breast cancer, visit the U.S. National Cancer Institute.

MONDAY, Dec. 10 (HealthDay News) -- About 5 percent of women considered at low risk for heart disease still face potential cardiovascular problems because of calcium buildup in their arteries, a new study suggests.

"Previous studies have demonstrated that calcium is predictive of coronary artery disease in other populations," said study lead author Dr. Susan G. Lakoski, a cardiology fellow at the Wake Forest University School of Medicine. "We traditionally have the question of looking at low-risk people."

The standard method of measuring heart risk is the so-called Framingham risk score, which is based on findings of a decades-long study of residents of a Massachusetts town. The score includes such factors as age, cholesterol levels, diabetes, smoking and obesity, but not calcium.

Lakoski and her colleagues used computerized tomography scans of the chest to measure coronary artery calcium in 3,601 women between 45 and 84 years of age. Ninety percent of the women were considered "low risk," because their Framingham scores indicated they had less than a 10 percent chance of a cardiac event in 10 years. (High risk is a test score of 20 percent or higher.)

Over an average of the next 3.75 years, 24 of the low-risk women had heart events -- such as heart pain or a heart attack -- and 34 of the women had a so-called cardiovascular disease event, including heart events, stroke or death, the study found.

Women with the highest calcium scores were especially at risk, Lakoski said. "They had an 8.6 percent risk of a coronary event," she said.

The findings are published in the Dec. 10/24 issue of Archives of Internal Medicine.

Lakoski said it's probably too early to consider routine testing of coronary artery calcium to gauge heart risk for women. The number of study participants was small, and further research is needed, she said.

Still, Dr. Suzanne Steinbaum, director of Women and Heart Disease at Lenox Hill Hospital in New York City, called the study findings important. "The risk of heart disease in women is often underestimated, because they develop heart disease later than men, often at age 65. By measuring calcium, we can show that they might actually be at higher risk, and that is important because they can benefit from preventive measures."

And heart-risk estimates for women based on traditional risk factors might be misleading because of societal changes, Steinbaum said. "Younger women are developing heart disease earlier than we originally thought," she said. "This is where calcium might be an important modality in classifying risk."

A test for coronary artery calcium is easily done, Steinbaum said, but health insurance companies don't currently pay for it.

While there are no known measures to reduce coronary artery calcium, a woman who knows of its presence can still take preventive measures, Lakoski said. "She needs to offset it with lifestyle measures that affect risk factors that are modifiable, such as cholesterol," she said.

More information

To learn more about coronary heart disease, visit the U.S. National Library of Medicine.

FRIDAY, Dec. 7 (HealthDay News) -- Scientists have discovered the mechanism by which a chemical known as perchlorate can collect in breast milk and cause cognitive and motor deficits in newborns.

Used since the 1940s to manufacture explosives and rocket fuel, the contaminant is still widely present in the water and food supply, experts say.

And high concentrations of perchlorate in breast milk can be passed to an infant and affect it's ability to manufacture essential thyroid hormone, the new study suggests. Perchlorate can also lessen the amount of iodide available to a mother to pass on to her infant, and a baby needs iodide to produce thyroid hormones.

"The deficit of thyroid hormone is particularly delicate if it's at the beginning of life because the central nervous system has not completely matured," said study author Dr. Nancy Carrasco, a professor of molecular pharmacology at Albert Einstein College of Medicine, in New York City.

Thyroid hormones are "absolutely critical" for the development and maturation of the central nervous system, skeletal muscles and lungs, she explained.

In laboratory and rat research, Carrasco's team found that perchlorate limited the amount of iodide transported to a mother's mammary glands. The only source of iodide a baby typically has is mother's milk, she explained.

Her team discovered that perchlorate accumulates in mother's milk, but before this study, "we didn't know it would be passed on as actively to the baby," she said.

Carrasco and her colleagues at Einstein and at Johns Hopkins University reached this conclusion after experimental studies on how sodium iodide carries perchlorate to, and concentrates it in, mammary glands.

The next steps in this research will include animal studies looking at the effects of perchlorate exposure during pregnancy, she said.

The debate continues on how much perchlorate is a high and harmful concentration, Carrasco said. But scientists have long known that iodide deficiency contributes to lowered IQ.

The new finding is relevant to the Environmental Protection Agency's standards for acceptable perchlorate levels, added R. Thomas Zoeller, a professor of biology at the University of Massachusetts-Amherst who has served on the EPA's peer review panels for the assessment of perchlorate.

At the time the current safety standards were established, the EPA was not thinking about how perchlorate is concentrated in breast milk, he said.

Zoeller said the study's discovery of how perchlorate is transported to breast milk is important to setting safety standards because perchlorate has a half-life of about eight hours and doesn't accumulate in the body. But because of the new findings, "we no longer have to debate whether perchlorate is being concentrated in milk," he added. "We have enough data to know that this is a very dangerous thing."

Large studies need to be done to confirm the findings, Zoeller added.

It's now "enormously important to find out if perchlorate in [breast] milk is affecting thyroid hormones in infants," he said. Such a study would be difficult to conduct because it would involve drawing blood from 1- and 2-week old infants, Zoeller said.

Tyrone Hayes, a professor of integrative biology at the University of California at Berkeley, said the discovery of a mechanism by which perchlorate can be transmitted to nursing infants is important.

"I think probably the most obvious significance is that we have a very common contaminant in the environment that has a profound negative impact, and that the most profound impact is on humans that don't have a choice at a critical development stage that can impact the rest of their lives," he said.

More information

The Environmental Protection Agency has more on perchlorate.

THURSDAY, Oct. 25 (HealthDay News) -- Women who undergo hysterectomies for benign conditions more than double their risk of needing subsequent surgery for stress urinary incontinence, a new study finds.

This was true regardless of what type of surgical technique was used for the hysterectomy, the researchers noted.

The article is published in the Oct. 27 issue of The Lancet, and although the study contradicts previous research, some experts said they are inclined to believe the current study.

"The authors have a lot of experience from previous studies, and they conducted this study using a very tight registry in Sweden. They had the opportunity to analyze the data almost in a unique way," noted Dr. Gil Levy, director of urogynecology at the Pelvic Floor Dysfunction and Reconstructive Surgery Center at Maimonides Medical Center in New York City. "When they come up with these results, it should be taken very seriously," he said.

According to background information in the study, many women opt to have a hysterectomy, because it can cure irregular heavy menstrual bleeding, uterine prolapse and postmenopausal bleeding. One in five British women will have undergone a hysterectomy by the time they reach 55. In the United States, 600,000 hysterectomies are performed each year, 90 percent of them for a benign indication (as opposed to cancer).

Studies regarding how a hysterectomy might affect lower-urinary-tract function have been inconsistent, however.

Female stress urinary incontinence is defined as involuntary leakage of urine upon effort or exertion. About 40 percent of women in most industrialized countries have the condition, with considerable effect on daily function as well as sexuality and psychological well-being.

This 30-year study, conducted between 1973 and 2003, involved more than 165,000 Swedish women who had undergone a hysterectomy and more than 479,500 women who had not.

The risk of having to undergo surgery for stress urinary incontinence was 2.4 times higher in the hysterectomy group than in the control group, regardless of what type of surgical technique was used for the hysterectomy.

The highest risk was during the first five years after the hysterectomy, when the risk was 2.7 times higher.

The lowest risk was more than 10 years down the line, when the risk was only 2.1 times higher for patients who had undergone a hysterectomy compared with those who had not.

The most logical explanation for the association, according to the authors, was surgical trauma that can occur when the uterus and cervix are detached from the pelvic-floor supportive tissues during a hysterectomy.

"This is a big, well done and population-based study," noted one outside expert, Dr. Tristi Wood Muir, assistant professor of obstetrics and gynecology, Texas A&M Health Science Center College of Medicine and director of female pelvic medicine and reconstructive surgery for Scott & White in Temple. "Certainly, the uterus and bladder are intimately related, and, certainly, dissecting the bladder off can cause problems down the road. When we do a hysterectomy, we have to reestablish support, and it may be that a lack of support is causing the stress urinary incontinence. But it could also be a whole host of other reasons. It could be any number of things."

According to the accompanying comment article, several other reasons might explain the incidence of stress urinary incontinence, some of which might have nothing to do with the hysterectomy.

Regardless of the cause, most of the experts agreed that hysterectomy is not something to be undertaken lightly.

"With any sort of surgical intervention, there are possible risks and side effects, and the way the body tissues and nerves react to incisions and stitches is quite variable between patients," said Dr. Jennifer Wu, an obstetrician/gynecologist at Lenox Hill Hospital in New York City. "This is something to consider when patients are thinking about surgery like a hysterectomy for a benign indication. There will always be some sort of need for hysterectomy whether it's for cancer or for severe bleeding or severe pain, but patients need to realize that while it can cure some problems, it can also be the source of other problems, so it is something patients will need to talk about with their doctors."

More information

There's more on urinary incontinence in women at the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.