Thursday, November 13, 2008

No link between IVF and breast cancer

Fears that IVF might raise women's risk of developing breast cancer have been dispelled by a nationwide study in the Netherlands, which has found that the fertility treatment has no effect on the disease.

While no link between IVF and breast cancer has been firmly established, some scientists have worried about the potential effects of fertility drugs used to stimulate the ovaries so that eggs can be collected and fertilised. These expose the body to high levels of oestrogen, a female hormone to which some breast tumours are sensitive. Some women who have had IVF and then gone on to develop breast tumours have blamed their condition on it. Sarah Parkinson, the late wife of the comedian Paul Merton, wrote before her death in 2003 of her belief that IVF had caused her cancer.

The new research, led by Alexandra van den Belt-Dusebout, of the Netherlands Cancer Institute, should reassure women considering fertility treatment that it does not pose a breast cancer risk. In the study, which was presented at the American Society for Reproductive Medicine conference in San Francisco, the Dutch team used a national registry to investigate more than 25,000 women who received IVF or other fertility treatments between 1980 and 1995. Almost 19,000 of the women had had IVF, while the other sub-fertile women had had different treatments or none.

There was no statistically significant difference in breast cancer incidence between either group as a whole and the general population. There was a slight increase in breast cancer risk among the infertility patients who had been followed up for the longest periods - 15 years - but this was accounted for by the size of their families. Women who seek fertility treatment tend to have fewer children than average, and to start having them later in life. Breast cancer studies must always correct for family size and childbearing patterns, because women who have more children at younger ages are known to be less likely to develop the disease. "After 15 years, the risk was a bit higher than in the general population, but this could be through a difference in the number of children compared to the general population," Dr van den Belt-Dusebout said. "When the hazard ratios are adjusted for parity [number of children] they are not significantly different."

The study also compared women who had had different numbers of IVF cycles, and found no relationship between extra cycles and breast cancer risk. This is important because women who have more cycles are exposed to higher amounts of drugs, and the lack of a dose-response relationship suggests there is no effect. "Our preliminary analysis indicates that for 15 years after IVF there is no increased risk of breast cancer compared to the female general Dutch population," Dr van den Belt-Dusebout said."

The study also revealed no significant differences in breast cancer risk between the infertile patients who had IVF and those who did not.

The findings support the outcome of a major review of the evidence published in 2004, which also found no causative link between IVF and breast cancer. The study even found that IVF may actually decrease breast cancer risk when it is successful, by allowing women to give birth and thus to gain the protective effect of having children.


A Doctor, a Mutation and a Potential Cure for AIDS

A Bone Marrow Transplant to Treat a Leukemia Patient Also Gives Him Virus-Resistant Cells; Many Thanks, Sample 61

The startling case of an AIDS patient who underwent a bone marrow transplant to treat leukemia is stirring new hope that gene-therapy strategies on the far edges of AIDS research might someday cure the disease. The patient, a 42-year-old American living in Berlin, is still recovering from his leukemia therapy, but he appears to have won his battle with AIDS. Doctors have not been able to detect the virus in his blood for more than 600 days, despite his having ceased all conventional AIDS medication. Normally when a patient stops taking AIDS drugs, the virus stampedes through the body within weeks, or days. "I was very surprised," said the doctor, Gero Huetter.

The breakthrough appears to be that Dr. Huetter, a soft-spoken hematologist who isn't an AIDS specialist, deliberately replaced the patient's bone marrow cells with those from a donor who has a naturally occurring genetic mutation that renders his cells immune to almost all strains of HIV, the virus that causes AIDS.

The development suggests a potential new therapeutic avenue and comes as the search for a cure has adopted new urgency. Many fear that current AIDS drugs aren't sustainable. Known as antiretrovirals, the medications prevent the virus from replicating but must be taken every day for life and are expensive for poor countries where the disease runs rampant. Last year, AIDS killed two million people; 2.7 million more contracted the virus, so treatment costs will keep ballooning.

While cautioning that the Berlin case could be a fluke, David Baltimore, who won a Nobel prize for his research on tumor viruses, deemed it "a very good sign" and a virtual "proof of principle" for gene-therapy approaches. Dr. Baltimore and his colleague, University of California at Los Angeles researcher Irvin Chen, have developed a gene therapy strategy against HIV that works in a similar way to the Berlin case. Drs. Baltimore and Chen have formed a private company to develop the therapy.

Back in 1996, when "cocktails" of antiretroviral drugs were proved effective, some researchers proposed that all cells harboring HIV might eventually die off, leading to eradication of HIV from the body -- in short, a cure. Those hopes foundered on the discovery that HIV, which integrates itself into a patient's own DNA, hides in so-called "sanctuary cells," where it lies dormant yet remains capable of reigniting an infection.

But that same year, researchers discovered that some gay men astonishingly remained uninfected despite engaging in very risky sex with as many as hundreds of partners. These men had inherited a mutation from both their parents that made them virtually immune to HIV.

The mutation prevents a molecule called CCR5 from appearing on the surface of cells. CCR5 acts as a kind of door for the virus. Since most HIV strains must bind to CCR5 to enter cells, the mutation bars the virus from entering. A new AIDS drug, Selzentry, made by Pfizer Inc., doesn't attack HIV itself but works by blocking CCR5.

About 1% of Europeans, and even more in northern Europe, inherit the CCR5 mutation from both parents. People of African, Asian and South American descent almost never carry it.

Dr. Huetter, 39, remembered this research when his American leukemia patient failed first-line chemotherapy in 2006. He was treating the patient at Berlin's Charite Medical University, the same institution where German physician Robert Koch performed some of his groundbreaking research on infectious diseases in the 19th century. Dr. Huetter scoured research on CCR5 and consulted with his superiors.

Finally, he recommended standard second-line treatment: a bone marrow transplant -- but from a donor who had inherited the CCR5 mutation from both parents. Bone marrow is where immune-system cells are generated, so transplanting mutant bone-marrow cells would render the patient immune to HIV into perpetuity, at least in theory.

There were a total of 80 compatible blood donors living in Germany. Luckily, on the 61st sample he tested, Dr. Huetter's colleague Daniel Nowak found one with the mutation from both parents.

To prepare for the transplant, Dr. Huetter first administered a standard regimen of powerful drugs and radiation to kill the patient's own bone marrow cells and many immune-system cells. This procedure, lethal to many cells that harbor HIV, may have helped the treatment succeed.

The transplant specialists ordered the patient to stop taking his AIDS drugs when they transfused the donor cells, because they feared the powerful drugs might undermine the cells' ability to survive in their new host. They planned to resume the drugs once HIV re-emerged in the blood. But it never did. Nearly two years later, standard tests haven't detected virus in his blood, or in the brain and rectal tissues where it often hides....

Blocking CCR5 might have side effects: A study suggests that people with the mutation are more likely to die from West Nile virus. Most worrisome: The transplant treatment itself, given only to late-stage cancer patients, kills up to 30% of patients. While scientists are drawing up research protocols to try this approach on other leukemia and lymphoma patients, they know it will never be widely used to treat AIDS because of the mortality risk.

There is a potentially safer alternative: Re-engineering a patient's own cells through gene therapy. Due to some disastrous failures, gene therapy now "has a bad name," says Dr. Baltimore. In 1999, an 18-year-old patient died in a gene therapy trial. Even one of gene therapy's greatest successes -- curing children of the inherited "bubble boy" disease -- came at the high price of causing some patients to develop leukemia.

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