WEDNESDAY, Dec. 5 (HealthDay News) -- A U.S. Food and Drug Administration advisory panel recommended Wednesday that the cancer drug Avastin should not be used to treat women with advanced breast cancer.

In a close vote, 5-4, the advisers decided the drug's ability to slow down the growth of tumors did not outweigh the increased risk of blood clots and other cardiovascular troubles among users, the Associated Press reported. In rare cases, patients taking Avastin with standard chemotherapy have died.

Avastin was approved to treat colon cancer in 2004, and lung cancer in 2006. It works by cutting off the tumor's blood supply.

"Everybody wants to offer metastic breast cancer patients hope, but we shouldn't offer them false hope," panel member Natalie Compagni-Portis, a patient representative with Breast Cancer Action in San Francisco, said during the meeting, according to the AP. "We have to raise the bar in terms of safety."

"These patients are terminal, and it's our job to make their lives better, not to say that it's OK to have a stroke or that it's manageable," Maha Hussain, an oncologist at the University of Michigan and the advisory panel's chairwoman, said during the meeting. "You didn't show that patients are living better or that they're living longer."

In trial results submitted to the FDA by the drug's U.S. maker, Genentech Inc., use of Avastin (bevacizumab) did boost the progression-free survival of women with advanced breast cancer by an average of 5.5 months, when combined with the chemotherapy drug paclitaxel. Progression-free survival refers to survival without any advancement of the malignancy.

However, the same Genentech study of 722 patients showed that patients reaped no gain in terms of their overall survival after taking Avastin.

Another company-funded trial, this time including 462 patients with advanced breast cancer, showed similar results, with Avastin having no effect on overall survival.

At the same time, the FDA said, the drug has "major safety issues," including hypertension, clotting events, left ventricular heart dysfunction, heart attack, gastrointestinal perforation and proteinuria (excess protein in urine). A special FDA staff review of the data found that rates of grades 3 to 5 toxicities rose by more than 20 percent when cancer patients received Avastin on top of regular chemotherapy.

Furthermore, in the Avastin-paclitaxel trial, the rate of patient deaths linked to Avastin use was 1.7 percent (six out of 363 users) compared to no deaths among the 348 participants who did not receive the drug, the FDA noted.

In its approval submission statement to the FDA, Genentech contended that, "Analysis of the safety and efficacy data in total demonstrates a highly favorable risk-benefit profile for bevacizumab in combination with paclitaxel that supports full approval of bevacizumab for the treatment of locally recurrent and metastatic breast cancer."

The FDA is not obligated to follow the recommendations of its advisory panels, but usually does. A decision is expected by Feb. 23, the AP reported.

Avastin is not traditional chemotherapy, but instead is a monoclonal antibody that robs tumors of their blood supply. It has been found to boost the survival of patients with metastatic colorectal cancer and non-small-cell lung cancer when added to chemotherapy and used as a first-line treatment.

But the drug has its downside. In an analysis of pooled data from five randomized controlled trials involving more than 1,700 patients with metastatic colon, breast or lung cancers, Genetech researchers found that 3.8 percent of patients experienced blood clots while on the drug, compared to 1.7 percent of those who took standard chemotherapy alone.

Patients who were 65 or older appeared to be at special risk for clots while taking Avastin, according to the study, which was published in August in the Journal of the National Cancer Institute.

The exact link between Avastin and cardiovascular risk remains unclear, although the Genentech team speculated that a vascular endothelial growth factor (VEGF), a natural compound that boosts blood vessel growth, may play a role.

More information

Find out more about breast cancer and its treatment at the American Cancer Society  .

TUESDAY, Nov. 27 (HealthDay News) -- Scientists have a developed a model to help doctors predict which postmenopausal women are likely to sustain a hip fracture over a five-year period.

The algorithm includes 11 different factors -- such as age and family history -- and applies to postmenopausal women of different ethnic backgrounds.

"Knowing the 5-year risk of fracture will permit patients to make informed choices when balancing ... lifestyle changes against undergoing medical interventions," explained a team led by Dr. John Robbins, of the department of internal medicine at the University of California School of Medicine, in Sacramento.

His group published their findings in the Nov. 28 issue of the Journal of the American Medical Association.

Some experts have predicted a coming epidemic of fractures among Americans over the next few decades as the population ages.

In particular, postmenopausal women are vulnerable to fractures resulting from osteoporosis, a degenerative weakening of the bones. About 329,000 hip fractures occur each year in the United States, according to the National Center for Health Statistics

The critical question is how to prevent such debilitating, and possibly fatal, fractures, and how to spot who's most at risk. Treatments that strengthen bone do exist, and might help shield people from fracture.

In devising the new algorithm, Robbins' team looked at data on almost 100,000 women who participated in the U.S. government-sponsored Women's Health Initiative (WHI).

The 11 predictors chosen were validated on 68,132 women and tested in 10,750 women who had undergone dual energy x-ray absorptiometry scans (DXA) to assess bone mass density.

The 11 factors that help predict hip fractures within five years are: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of fracture after age 54, parental history of hip fracture, current smoking, current corticosteroid use and treated diabetes.

The model still needs to be tested in diverse populations, the authors pointed out. And it doesn't identify which women would benefit from which specific prevention measures. "However, we believe [the] 11 readily available clinical variables offer a simple means of stratifying the 5-year risk of hip fracture in postmenopausal women," they concluded.

One outside expert thinks the model will help.

"This gives us a way to pinpoint which women need aggressive preventative therapy," said Paul Brandt, an associate professor of neuroscience and experimental therapeutics at Texas A&M Health Science Center College of Medicine in College Station.

More information

Find out more on osteoporosis at the American Academy of Orthopaedic Surgeons.

MONDAY, Nov. 26 (HealthDay News) -- Premenopausal women struggling with depression have lower bone mass than do non-depressed women in the same age range, a new study found.

The bone loss was most pronounced in certain regions of the hip, which is troubling given that hip fractures are one of the most serious -- and potentially fatal -- consequences of osteoporosis.

The level of bone loss seen in the depressed women was the same or higher than that associated with other, established risk factors for osteoporosis, including smoking, low calcium intake and lack of physical exercise, the researchers said.

The findings, published in the Nov. 26 issue of the Archives of Internal Medicine, could have implications for the prevention of osteoporosis.

"Premenopausal women with depression should be screened for low bone mass," said Dr. Giovanni Cizza, senior author of the study who conducted the research while at the U.S. National Institute of Mental Health. "They should do a bone mineral density measurement, because osteoporosis is a silent condition. Until someone fractures, you don't know you have osteoporosis."

Cizza is now a staff clinician at the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

A woman's bone mass peaks during youth then thins after menopause. Previous, preliminary studies had suggested that depression might be a risk factor for low bone mass in older women.

For this study, Cizza and his colleagues looked at 89 women with depression and 44 women without depression. The women ranged in age from 21 to 45. The depressed women were taking antidepressant medications.

Seventeen percent of the depressed women had thinner bone density in the femoral neck, a vulnerable part of the hip. Only 2 percent of non-depressed women, by contrast, had thinner bone in this area.

Twenty percent of depressed women also had low bone density in the lumbar spine, compared with 9 percent of the non-depressed women.

Blood and urine samples also revealed that the depressed women had lower levels of "good" proteins called cytokines. "The bad cytokines that may cause bone loss are higher," Cizza said.

It's not clear what role antidepressants might play, but by relieving the depression, the drugs may also help bone mineral density, the researchers said.

More information

To learn more about bone health, visit the National Osteoporosis Foundation  .

WEDNESDAY, Nov. 21 (HealthDay News) -- Researchers have identified the chemical pathway by which a mother's smoking before and after pregnancy might reduce her daughter's fertility by as much as two-thirds.

Cigarette smoking during pregnancy has been shown in retrospective studies to affect the fertility of a woman's offspring, but this is the first study to offer an explanation of the biology behind the effect, the Canadian scientists claim.

A team at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto investigated the impact of polycyclic aromatic hydrocarbons (PAH), a byproduct of smoking, on mouse fertility.

Researchers injected three groups of female mice with a low-dose mixture of PAH: One group received PAH before conception and again when they were providing milk for their pups; one group received PAH only before conception; and the third group received PAH only during lactation. A fourth control group did not receive PAH but were mated at the same time as the others. The total amount of PAH given to each mouse over the three-week injection cycle was equivalent to 25 packs of cigarettes, according to the researchers. The exposed mice did not have fewer pups in their own litters, but when researchers investigated the number of eggs in their female offspring, they found about 70 percent fewer follicles available to produce eggs.

"Mothers, mice in this case, exposed to PAHs -- environmental pollutants found in cigarette smoke, car exhaust, smoke produced by fossil fuel combustion, as well as in smoked food --before pregnancy and/or during breast-feeding, but not during pregnancy, can cause a reduction in the number of eggs in the ovaries of their female offspring by two-thirds. This limits the window in which the daughter will be able to reproduce," explained lead researcher Dr. Andrea Jurisicova.

Further analysis indicated that the effects of PAHs on the number of follicles in female offspring were mediated through a receptor that affects the expression of a gene that makes a protein that causes cells to die. The researchers then demonstrated similar effects in human ovarian tissue transplanted into immunocompromised mice.

Jurisicova described the process: "Toxic compounds were injected under the skin of mice and were picked up by the bloodstream and carried throughout the body until they reached the ovaries. Once at the ovaries, they passed through the cell membrane and bound to the receptor. When this happens, it activates the receptor, which then enters the cell nucleus. The receptor then finds a specific DNA sequence that turns on the gene, which accumulates and eventually kills the eggs."

"This study now is providing a chemical pathway, which is very nice," said Dr. Norman Edelman, consultant for scientific affairs with the American Lung Association. The new data provides biological support for epidemiological results, such as the previously observed reduction in fertility among daughters of smoking women, he added.

Whether the news will have an impact on a woman's decision to smoke is another question, said Edelman.

"If we do our job right and these results get good press, this data could remind women of what they are doing to their unborn fetuses," Edelman said.

Another expert noted this latest finding adds to a growing body of evidence that shows a strong connection between smoking and fertility.

"I think it is an interesting study, but it doesn't add much new. Other studies have shown similar outcomes. The theory is that smoking could affect the follicles or the fallopian tubes," said Dr. Amos Grunebaum, director of obstetrics at New York Weill Cornell Medical Center, in New York City. "We have known for many years that smoking affects fertility on many levels."

"The key is women should quit smoking before they are thinking of getting pregnant," Grunebaum said.

The Canadian researchers did offer some good news in their report, published in the Dec. 3 edition of the Journal of Clinical Investigation. Injecting resveratrol in the mice who were exposed to PAH prevented the reduction in egg follicles in their offspring. Resveratrol is a naturally occurring antioxidant found in wine and grape skins. However, that reversal of damage does not mean that women who smoke can counter the effects with a nutritional supplement or a glass of red wine, the researchers stressed.

"We have found that oral consumption of resveratrol as a food supplement, at least in mice, is not effective, as levels of resveratrol do not reach sufficient amount in the bloodstream to provide protection," Jurisicova said.

Although the findings do not define the length of time between quitting smoking and healthier fertility in offspring, Jurisicova noted that previous studies have shown that women who smoke have better results with in vitro fertilization one year after they quit smoking. The mice in the current study conceived up to two weeks after their final PAH injection, which is approximately equivalent to three menstrual cycles in women.

The effect of a mother's cigarette smoking is not limited to her female children. A study published in the Jan. 1 issue of the American Journal of Epidemiology suggested that the male offspring of mothers who smoke have lower sperm counts.

There is still more research to be done, Jurisicova noted.

"We hope to continue studying the female offspring to see if they enter the mouse version of menopause earlier than mice whose mothers were not exposed to PAHs," Jurisicova said. "We also hope to study if their reduced fertility passes on to subsequent generations, and if the granddaughters are predisposed to similar problems."

More information

Need to quit smoking? Visit the U.S. Surgeon General or the National Institutes of Health.