March 9th, 2010 
Exposing a female fetus to a chemical found in plastics causes permanent changes in a daughter’s uterus that might result in cancer – and a research team led by a Yale doctor has figured out why.
Bisphenol A is commonly found in plastics (those with a “7″ code on the bottom), in the lining of aluminum cans and in dental sealants. The U.S. Food and Drug Administration has expressed concern about potential effects of BPA on the brain and reproductive organs, though the link is not definitive.
Dr. Hugh S. Taylor, director of reproductive endocrinology and infertility section of the Yale School of Medicine, said even brief exposure to BPA in the uterus causes permanent damage.
“We already know that mice that are exposed to BPA already have a higher risk of breast cancer, uterine cancer and infertility,” he said.
In this study, one group of mice was exposed to BPA as fetuses and compared to a control group to see how much the DNA in the uterus had been modified. The findings, Taylor said, reveal that BPA strips off a part of the DNA, which permanently alters the genetic structure.
“It chemically modifies the DNA by removing methyl groups from the DNA backbone and that makes the DNA more accessible,” he said. The genes then become permanently altered to be supersensitive to estrogen, which can lead to cancer and other consequences.
He said the damage might occur in females after birth as well.
“It’s not as clear,” he said. “It very well may be. I think that’s still more controversial. I think pregnancy is the more dangerous time.”
Taylor said the effect of BPA is reminiscent of the problems with DES (diethylstilbestrol), which was prescribed to women from 1938 to 1971 to prevent miscarriages, according to the Centers for Disease Control and Prevention. DES was linked to a rare form of vaginal cancer.
“Now it looks like (as they grow older) those women who were exposed as a fetus have a higher risk of breast cancer,” Taylor said. He also is studying a potential link between BPA and breast cancer.
Taylor said it’s a good idea for women who may become pregnant to avoid BPA, especially products that are brand new and unwashed or old and cracked. Plastics with BPA shouldn’t be microwaved, he said.
Environmental groups also have called for BPA to be removed from consumer products; some companies have begun manufacturing BPA-free items, such as water bottles.
“I always tell my patients, as a physician as well as a scientist … to me it’s an easy decision. There’s so much benefit of eating fresh vegetables instead of (eating) out of a can,” he said.
Related
- Pregnancy Safe For Breast Cancer Survivors
Women who survive breast cancer and have children afterwards don’t appear to be at any higher risk of dying from cancer, a new study says.
Doctors have long worried pregnancy might spark hormonal changes in breast cancer survivors that could spur the disease’s return, and many breast cancer patients are counseled against getting pregnant after they recover.
In research presented Friday at a European breast cancer conference in Barcelona, experts said pregnancy in women who have been treated for breast cancer is safe and does not seem to be linked with the disease’s recurrence.
Among women in the general population, those who have early and multiple pregnancies have a lower risk of getting breast cancer than women who don’t.
Dr. Hatem Azim of the Institute Jules Bordet in Belgium and colleagues analyzed results from 14 previous trials that followed more than 1,400 pregnant women with a history of breast cancer. Those women became pregnant several months to several years after finishing treatment. Azim and colleagues compared those women to more than 18,000 women who had had breast cancer and were not pregnant.
Azim and colleagues found that the women who got pregnant had a 42 percent lower risk of dying compared with breast cancer survivors who did not get pregnant. He said part of that benefit might be due to the fact that women who were naturally healthier were those that later had children.
But in some studies, women with breast cancer who became pregnant were compared to women who remained free of the disease, i.e. the healthiest of the breast cancer survivors.
“For many years, pregnancy was considered a risk for women who had breast cancer,” said Maria Leadbeater, a cancer expert at Breast Cancer Care, a British charity. “But this study seems to show the risk is not an issue once you’ve been treated,” she said. Leadbeater was not connected to Azim’s study.
Leadbeater said the advice for patients might vary depending on the type of breast cancer they’ve had and how they responded to treatment. Women who need hormone therapy for breast cancer typically need to be on it for five years — during which time doctors recommend against getting pregnant.
Leadbeater and others said women should try to wait until two years after their diagnosis to try for a baby, since that is thought to be the riskiest time for a relapse.
Azim, who led the study, hypothesized that the relationship between hormones and breast cancer might be more complicated than doctors initially thought. Estrogen is known to trigger breast cancer and women typically have more estrogen when they’re pregnant. But very high doses of the hormone can also kill cancer cells, Azim said.
Other hormones that are elevated in pregnancy, like the one for breast-feeding, have been proven to protect against breast cancer. “What we are seeing is only the tip of the iceberg,” Azim said. “It’s too simple to say that pregnancy stimulates hormones and that’s bad for breast cancer.”
- Pregnant women with breast cancer face good odds of recovery
Pregnant women who develop breast cancer do not have worse odds of death or of cancer returning than other young breast cancer patients, a recent study has found.
The study is one of the largest to look at whether breast cancer hits pregnant and recently pregnant women harder than other women. It contradicts some smaller, earlier studies that suggested maternity made things worse.
“If we can get them early, we can treat them aggressively and have good and promising outcomes for both woman and child,” said the study’s lead author, Dr. Beth Beadle of the University of Texas M.D. Anderson Cancer Center.
Frightening for any woman, a breast cancer diagnosis is particularly terrifying for a pregnant woman. It presents complicated decisions about how to treat the mother and not harm the fetus. Some doctors recommend abortion so they can focus on treating the mother.
In the new study, published earlier this year in the journal Cancer, researchers analyzed data from 652 women ages 35 and younger who were treated for breast cancer at M.D. Anderson from 1973 through 2006.
The study group included 104 women with pregnancy-associated cancers —- 51 who had breast cancer during pregnancy, and 53 who developed the illness within a year after.
The rates of cancer recurrence, cancer spread and survival were about the same for the women with pregnancy-associated breast cancers as they were for the other women, the researchers found. The researchers calculated the rates for 10 years after the cancer diagnosis.
The women who were pregnant had tumors at a more advanced stage, probably because women and their doctors may have discounted breast changes, attributing them to breast feeding or pregnancy, the researchers believe.
Generally, breast cancers are more aggressive in younger women, and survival rates are significantly lower. While age may be a factor, it’s not clear that pregnancy is: There was no evidence in the new study that tumors were faster growing in the pregnant women, said Beadle, a radiation oncologist.
Radiation —- dangerous to a fetus —- is commonly used in mammography and breast cancer treatment. But ultrasound can be used to look for breast tumors instead. And surgery and certain kinds of chemotherapy can treat the cancer without poisoning the womb.
However, it remains a complicated medical situation that can depend on the severity of the cancer and how far into the pregnancy the mother is, said Dr. Ruth O’Regan, an associate professor at Emory University’s Winship Cancer Institute in Atlanta.
- Migraine drugs don’t up birth defect risk: study
A study in nearly 70,000 pregnant women has found no link between migraine drugs called triptans and the risk of birth defects.
However, the researchers did find a “slight increase” in the risk of excessive bleeding during labor, and the failure of the uterus to contract normally after delivery, for women who used the drugs while pregnant.
Triptans are among the most powerful drugs used for migraine; others include aspirin, Excedrin, and ibuprofen.
While as many as three in 10 women may develop migraines during their childbearing years, women often shy away from using such drugs during pregnancy because of safety concerns, according to study co-author Katerina Nezvalova-Henriksen of the University of Oslo in Norway and her colleagues.
However, the authors of the study in Headache note, untreated migraine may itself carry risks for mother and child; some studies have linked it to pre-eclampsia, a potentially deadly pregnancy complication.
“While it is important to exert caution when using any medications during pregnancy, this study indicates” that pregnant women can either start or continue taking triptans without “any major risk” of miscarriage, premature delivery, or other bad outcomes, the authors conclude.
Nezvalova-Henriksen and her team studied nearly 70,000 women. Two percent, or 1,535, had used sumatriptan (Imitrex), rizatriptan (Maxalt), zolmitriptan (Zomig), or eletriptan (Relpax) in pregnancy.
Less than one percent — 373 women — had used the drugs before getting pregnant but not during pregnancy.
The overall birth defect rate, which encompasses everything from large birthmarks to serious heart problems, was the same among women who had taken triptans during pregnancy and those who didn’t have migraines: 5 percent. Among those who had used triptans in the past but not during pregnancy, it was slightly higher: 6 percent.
The women who used triptans were also more likely than non-triptan users to take other drugs during pregnancy, including acetaminophen (Tylenol) with codeine and non-steroidal anti-inflammatory drugs such as ibuprofen.
However, the rate of major birth defects – such as serious problems of the limbs or internal organs — was 3 percent for all three groups. That rate – about one in 33 births – is about what would be expected for all birth defects in the general population.
The researchers did find that women who used triptans in their second or third trimester were more likely to develop a condition called atonic uterus, in which the uterus fails to contract back to its normal size after delivery. This is the leading cause of excessive bleeding after delivery. They were also more likely to lose significant amounts of blood during labor and delivery.
And during pregnancy, they were more likely to suffer from vomiting than women who had never used the drug; they were also more likely to develop pre-eclampsia or eclampsia, and more likely to have deficiencies in the B-vitamin folate.
While many women who suffer migraines will experience improvements in their symptoms after their first trimester, Nezvalova-Henriksen and her team note, those whose symptoms don’t improve by then aren’t likely to get better.
- Exposure to passive smoking during pregnancy ‘increase children’s risk of cancer in later life’
Pregnant women subjected to passive smoking give birth to babies with an increased, lifelong susceptibility to cancer, research reveals.
Passive smoking causes the same type of genetic damage in unborn infants as that found in adult smokers with cancerous tumors.
Researchers said the abnormalities in newborns were indistinguishable from those found in babies of mothers who were active smokers.
And they may affect survival, birth weight and lifelong susceptibility to diseases like cancer, according to the study published online in the Open Paediatric Medicine Journal.
Dr Stephen Grant and colleagues at the University of Pittsburgh in the U.S. found a smoke-induced mutation in an oncogene, a gene which transforms normal cells into cancerous tumors.
The mutation was the same level and type in newborns of mothers who were active smokers as those in babies born to non-smoking mothers exposed to tobacco smoke.
The mutations were also discernible in newborns of women who had stopped smoking during their pregnancies, but who did not actively avoid second-hand smoke.
The study confirms previous research in which Dr Grant discovered evidence of genetic abnormalities in babies whose mothers were exposed to environmental tobacco smoke.
There is also evidence that maternal exposure to passive smoke, as well as a history of paternal cigarette smoke exposure, is linked with an increased risk of childhood cancer, especially leukaemias and lymphomas in children under five.
Dr Grant said: ‘These findings back up our previous conclusion that passive, or secondary, smoke causes permanent genetic damage in newborns that is very similar to the damage caused by active smoking.
‘By using a different laboratory test, we were able to pick up a completely distinct yet equally important type of genetic mutation that is likely to persist throughout a child’s lifetime.
‘Pregnant women should not only stop smoking, but be aware of their exposure to tobacco smoke from other family members, work and social situations.’
- Pregnant women confront rise in cancer cases
The number of women diagnosed with breast cancer during pregnancy or soon after giving birth has more than doubled since the 1960s, and researchers say cases will continue to rise as women have children later in life.
The incidence of pregnancy-associated breast cancer rose from 16 in every 100,000 deliveries to 37.4 per 100,000 deliveries between 1963 and 2002, a study has found.
Breast cancer was under-diagnosed in pregnant and breastfeeding women because they and their doctors assumed breast firmness or lumps were a normal part of childbearing, said the chief executive of the National Breast and Ovarian Cancer Centre, Helen Zorbas.
She urged health professionals to assess all women the same way, regardless of pregnancy. ”While most breast changes won’t be cancer, early detection is vital for improving survival.”
Although pregnancy does not cause breast cancer, hormonal changes can accelerate its growth and tumours in pregnant women are often larger and more advanced by the time they are detected than those in women who are not pregnant.
The disease poses a dilemma for patients and their doctors. Pregnant women can have surgery but not radiotherapy. And chemotherapy is allowed only after the first trimester.
The study, published in the journal Obstetrics & Gynecology, reviewed more than 4.1 million deliveries in Sweden between 1963 and 2002.
The Karolinska Institute in Stockholm found the largest proportion of pregnancy-related breast cancers was among 25- to 29-year-olds.
But because the breast cancer risk rose with age and the average age of mothers had increased to about 30, its incidence during pregnancy was likely to increase, the institute said.
