1Cancer Epidemiology Unit, University of Oxford, England.
2Clinical Trial Service Unit, University of Oxford, England.
*Corresponding author. Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK. E-mail: kirstin.pirie@ceu.ox.ac.uk
Background Active smoking has little or no effect on women's risk of developing breast cancer, but it has been suggested that passive exposure to tobacco smoke may increase this risk among women who have never smoked.
Objective To evaluate the possible relationship between passive smoking and breast cancer risk within the Million Women Study, a large UK prospective study, and to report a meta-analysis of published results.
Methods In the large prospective study, 224 917 never smokers who completed a questionnaire that asked women whether their parents had smoked and if their current partner smoked were followed up for an average of 3.5 years for incident breast cancer. In the meta-analysis, studies that had recorded exposure information prospectively and retrospectively were considered separately.
Main outcome measures Adjusted relative risk of breast cancer in never smokers who were passively exposed to tobacco smoke at various ages compared with never smokers with no such exposure.
Results In the prospective study, 2518 incident invasive breast cancers occurred during follow-up and the adjusted relative risk of breast cancer for passive exposure either as a child or as an adult vs neither exposure was 0.98 (95% CI 0.88–1.09); results were similarly null for childhood exposure (0.98, 0.88–1.08) and adult exposure (1.02, 0.89–1.16) separately. We identified seven other studies with prospectively recorded exposure data; when results of all eight studies were combined (including 5743 never smokers with breast cancer), the aggregate relative risk was 0.99 (0.93–1.05) for any passive exposure. The aggregate findings differed substantially (P = 0.0002) between these 8 studies and 17 other studies with retrospectively recorded information (including 5696 never smokers with breast cancer).
Conclusions Aggregate results from studies with prospectively reported information show that the incidence of breast cancer is similar in women who did and did not report passive exposure to tobacco smoke either as a child or as an adult. The aggregate findings from the retrospective studies may have been distorted by some women becoming more likely to report past exposures because they knew that they had breast cancer.
Keywords Passive smoking, female breast cancer, prospective cohort study, meta-analysis
City women at greater risk for breast cancer
Nov. 26 2007
CTV.ca News Staff
Women who live in cities have denser breasts than those who live in suburban and rural areas, making them more likely to develop breast cancer, according to a study presented Monday at the annual meeting of the Radiological Society of North America.
Breast tissue in women may be fatty or glandular or a mixture of both. Density decreases with age; on average, women lose about one per cent of their breast density each year.
The only way to know what kind of breasts a woman has is to have a mammogram.
Women with more glandular breasts show denser tissue on a mammogram. They are known to have nearly four times the risk of developing breast cancer than women with fatty breasts.
A Canadian study published earlier this year, in the New England Journal of Medicine, found that women with dense breasts are at about five times greater risk of developing breast cancer compared to those with little or no dense tissue.
The study also found that in addition to increasing risk of breast cancer, dense tissue makes tumours more difficult to spot in a mammogram. That thereby increases the risk of cancer development between tests.
For this latest study, Dr. Nicholas M. Perry, director of The London Breast Institute at The Princess Grace Hospital in London, U.K., says his findings suggest the need for urban women to be more vigilant about their breast cancer screening.
"Women living in cities need to pay more attention to having regular breast screening," he said.
"Currently, women who live in urban areas are known to have lower attendance for breast screening programs than women in outlying areas."
Perry led a team that set out to determine if there was a relationship between breast density and area of residence.
They analyzed digital mammograms of 972 women from urban, suburban and rural areas. They discovered that women who lived in London had significantly denser breasts than those living outside the city. The team found:
• Among rural women, 69 per cent had dense breasts
• Among suburban women, 74 per cent had dense breasts
• Among urban-dwelling women, 78 per cent had dense breasts
The risk of increased density was twice as great in the 45- to 54-year-old group. The differences by area were more pronounced in women under age 50.
Perry says he had noticed for years that women in rural areas had less dense breasts than women in city.
"I work all my time in the city of London and I read mammograms of very dense breasts. But every time I have gone outside to read mammograms elsewhere in more rural areas or parts of Europe that are rural, I am very impressed with the less dense breast tissue that is there," he told CTV.
"I have talked to some of my colleagues who also read a lot of mammograms in different areas and they agree, so I thought it was about time to do the study."
Causes of breast density unclear
It's unclear why women living in urban areas have denser breasts. There may be environmental factors at work. Or it may be because of differences in lifestyle, such as obesity and exercise rates or stress levels. Hormonal birth control may also play a role.
Dr. Roberta Jong, the head of breast imaging at Sunnybrook Health Sciences Centre in Toronto says the urban-rural differences may also be related to childbearing.
"Having children earlier and having more children may be more common for women who live in rural areas than women who live in urban areas, where they may be more career-oriented. So that may be a factor," she speculates.
But Dr. Kefah Mokbel, a consultant breast surgeon in London, who also contributed to the study, says he doesn't think that a woman's reproductive history is relevant. He says he believes air pollution particles called "polycyclic aromatic hydrocarbons" are causing the problem. These particles mimic female sex hormones and can disrupt normal hormonal functions.
"We have significant evidence that traffic emissions can cause estrogen-like activity on the breast, particularly a city like London with a lot of fog all year," he told CTV News.
"These particles don't rise high among the atmosphere. We inhale these particles and when we inhale they enter the lungs and the bloodstream."
Perry says more research is needed to identify the different causes.
"But we're left with the fact that women in the city are at high risk of breast cancer, they have denser breast tissue on mammograms, and what can we do about it?" he said. He says there are two things that can be done:
• Firstly, make sure women in the city have access to high quality breast screening programs.
• Ensure that digital mammography is available, since it is superior for examining women with dense breasts.
Jong agrees that digital mammography provides doctors with clearer images, but she says some Canadian women may have trouble getting access to the technology.
"Only a small percentage of facilities have digital mammography, so it is better for a woman to get a mammogram than not get a mammogram at all if she does not have access to digital."
Another study presented on Monday at RSNA 2007 looked at the influence of the Western lifestyle on breast composition.
Dr. Miriam Sklair-Levy from Hadassah Medical Center in Jerusalem compared breast densities of Israeli women and Ethiopian women who immigrated to Israel. Her team found that Ethiopian-born women who have immigrated to Israel had significantly lower breast density than did Israeli-born women.
In addition, past Ethiopian immigrants who had begun to adopt a Western lifestyle (decreased number of children, change in diet or increased hormone use) had significantly higher breast density than recent immigrants.
With a report from CTV's Avis Favaro and producer Elizabeth St. Philip
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City women at greater risk for cancer
November 27, 2007 at 9:51 AM EST From Tuesday's Globe and Mail
ANDRÉ PICARD
New research suggests that women living in urban areas have denser breasts - a significant danger factor
There are many factors that influence a woman's risk of developing breast cancer, including genetics, age, diet, exercise, income and a number of reproductive and hormonal milestones such as age at first menstruation, age when she gives birth, late menopause and using birth control pills or hormone replacement therapy.
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Daughters linked to higher prostate cancer risk Jan. 3 2007
Men who father daughters, not sons, are more likely to develop prostate cancer, according to a new study released on Wednesday.
The researchers found men with three daughters and no sons were up to 60 per cent more likely to develop prostate cancer.
Prostate cancer is the most common male cancer. It affects the prostate, a gland the size of a walnut under the bladder that makes fluid for semen.
Researchers at Columbia University's Mailman School of Public Health in conjunction with Jerusalem's Hebrew University looked at more than 38,000 men and compared the families of the more than 700 diagnosed with prostate cancer with those of the other men.
The findings, published in the most recent issue of the Journal of the National Cancer Institute, show the relative risk of prostate cancer drops as the number of sons increases.
"We surveyed vital status and cancer incidence, and found a strong trend for a decrease in prostate cancer risk as the number of sons increased," said Dr. Susan Harlap, professor of clinical epidemiology at the Mailman School of Public Health, and the leader of the research team.
"We anticipate that this finding will have a significant impact on the direction of research in this field going forward," Harlap, who led the research team, said in a written statement.
Overall, men with only daughters were 40 per cent more likely to develop prostate cancer.
The risk increased when a man had three or more daughters and no sons.
The researchers suggested the risk of prostate cancer increased because of health screening.
It was also possible that a predominantly female family may encourage a man to be more health-conscious, they said.
The researchers also suggested men with several daughters may seek medical attention to find out why they hadn't fathered a son.
However, many experts discount those theories and say the increased risk is linked to genetics.
The study suggests the cause of an increased risk may be the male "Y" sex chromosome, which could not only affect the likelihood of having boys but lead to cancer development.
The offspring's sex depends on whether it receives an X or a Y chromosome from the father. A man with a damaged Y chromosome will be less likely to have sons.
"Our findings suggest that the biological significance of lack of sons -- whatever it is that leads to increased risk of prostate cancer -- becomes increasingly important as family size increases," Harlap said.
"Overall, our findings are consistent with hypotheses that tie Y chromosome loci to prostate cancer, although other explanations cannot be excluded," she added.
In addition to Columbia University's Mailman School of Public Health and Department of Psychiatry, the international team of scientists included researchers from Jerusalem's Hebrew University-Hadassah School of Public Health and the Braun School of Public Health.
The Canadian Cancer Society estimates that 20,700 men in this country will be diagnosed with prostate cancer this year and 4,200 will die from the disease.
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Exercise Can Reduce a Smoker’s Lung Cancer Risk, but Quitting Still Most Important
Description
In a study of more than 36,000 women, researchers observed that smokers can reduce their risk of developing lung cancer by being physically active. However, they strongly caution that any relative benefit is dwarfed by the benefits gained from quitting smoking.
Newswise — In a study of more than 36,000 women, researchers observed that smokers can reduce their risk of developing lung cancer by being physically active. However, they strongly caution that any relative benefit is dwarfed by the benefits gained from quitting smoking.
The researchers, from the Universities of Minnesota and Pennsylvania, report in the December issue of Cancer Epidemiology Biomarkers & Prevention that a high level of physical activity in women who smoked reduced their relative risk of developing lung cancer by 72 percent. Moderate activity among smokers was associated with a 65 percent risk reduction, and lower relative risks were also seen in former smokers who had moderate or high activity levels.
While this may sound like welcome news to female smokers who don’t want to quit, the investigators emphasize that the absolute risk of developing lung cancer is still much greater in current and former smokers regardless of activity level.
“The most important thing a smoker can do to reduce risk is to quit smoking. That said, exercising and being active can offer a marginal change in risk,” said the study’s lead author, Kathryn Schmitz, Ph.D. an assistant professor at the University of Pennsylvania. Schmitz worked on the study with a team of researchers while on faculty at the University of Minnesota.
In other words, she says, a physically active smoker has a 35 percent lower risk of lung cancer than a sedentary smoker, but if both smokers quit, they would both reduce their risk by as much as 10- or 11-fold. “Smokers who exercise are at a 35 percent lower risk of developing lung cancer relative to smokers who don’t exercise, but if you smoke at all, your risk of developing lung cancer is 10- to 11- fold higher than if you didn’t smoke.”
“The helpful message from this study is that if a smoker is having trouble quitting, exercise can be a first step toward better health,” says Schmitz.
The findings were derived from the Iowa Women’s Health Study, which in 1986 began to follow almost 42,000 women between the ages of 55 and 69. Over the years, five questionnaires were sent to the participants who recorded their smoking status and physical activity among other variables. This analysis, which began in 2002, included 36,410 participants, including 777 women diagnosed with the cancer. Among this group, 125 were non-smokers, 177 were former smokers, and 475 were current smokers.
Compared to women who were physically active, women with a low physical activity level at the baseline analysis were more likely to smoke, less likely to have a high school education and more likely to be obese.
Among smokers, the most number of cancer cases (324) were seen among women who currently smoked and had low activity, and the lowest number (40) was in the group of women who formerly smoked and were highly active. Compared to never smokers, current and former smokers had proportionally more squamous cell and small-cell lung cancer, which can be harder to treat than other subtypes.
Researchers don’t know why activity could lower lung cancer risk, but suggest that improved pulmonary function may reduce both the concentration of carcinogenic particles in the smoker’s airway and the extent to which they are deposited in the lungs. They also theorize that exercise training improves immune function and reduces the inflammatory responses that can impact cancer development.
“This may be useful information for smokers who are not currently willing to attempt smoking cessation or have recently failed a quit attempt,” says Schmitz. “But even if there was a significant risk reduction, quitting smoking is unarguably the most important action a person can take for reduction of lung cancer risk.”
The study was funded by the National Cancer Institute.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
Milk thistle drug blocks lung cancer in mice
Jun 27, 2006
Martha Kerr
Silibinin, a drug derived from milk thistle, destroys lung cancer in mice, investigators at the University of Colorado, Denver report in the Journal of the National Cancer Institute.
Lead investigator Dr. Rana P. Singh told Reuters Health, "We have been studying milk thistle components, silymarin and silibinin, to examine their efficacy and mechanisms against different...cancers for over a decade."
In the current study, Singh's team injected mice with a chemical called urethane to induce lung cancer. The animals then received diets containing different doses of silibinin.
"We obtained pure silibinin from Sigma Chemical Co., and silibinin diets were commercially prepared at room temperature and air dried. We did not use milk thistle dietary supplements which are available for human consumption," Singh said.
Mice fed silibinin had fewer large lung tumors than untreated mice. Further analysis showed that silibinin seemed to reduce the number of blood vessels that provide nutrients to the tumors, allowing them to grow.
Singh added that further laboratory studies of silibinin for lung cancer are now being done. "We expect soon after that clinical trials with silibinin in lung cancer patients will be planned."
Human trials of silibinin are already underway for the treatment of prostate cancer.
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Genes linked to spread of breast cancer discovered
July 27, 2005
LONDON (Reuters) - Scientists have identified genes enabling breast cancer cells to spread to the lungs, a discovery that could improve diagnosis and treatment of the disease.
The set of genes not only reveals where the cancer will spread, but also how virulent it is likely to be. The genes could be potential targets for existing or new breast cancer drugs, according to the researchers.
"We have looked for and found a specific set of genes that some breast cancers utilize to form metastasis to the lungs specifically," Dr Joan Massague, of the Howard Hughes Medical Institute at the Memorial Sloan-Kettering Cancer Center in New York, said on Wednesday.
The lungs, with the bones, liver and brain, are the main organs to which breast cancer spreads. For each organ the cancer invades it needs a specific set of genes.
The findings reported in the science journal Nature are important because if breast cancer is diagnosed and treated early, women have a better chance of beating the disease.
After it has spread beyond the breast it is more deadly because treatments are less effective.
Breast cancer is one of the most common cancers in women worldwide. More than a million new cases occur each year, according to the International Agency for Research on Cancer in Lyon, France.
MEDIATORS FOR METASTASIS
The genes which can be found in some primary breast tumors seem to predict a high risk of spread to the lungs even years later.
The discovery could help doctors to identify women whose cancer is most likely to spread to the lungs so they can closely monitor them and try to block it, or treat it as early as possible.
Massague and his team discovered the pattern of gene activity by studying tumors from 82 patients whose breast cancer had spread to the lungs.
They analyzed data from a similar group of patients from the Netherlands and found the same genetic signature.
Massague said the genes were not just markers for cancer spreading, but were also mediators that caused it to spread. The proteins they produced could become prime targets for existing or new drugs to prevent metastasis -- the spread of cancer.
"Compounds already exist to block some of the genes we have identified or the cell function they regulate. The next step is to begin testing these compounds in animal models to see if they can block metastasis," Massague said.
If someone is diagnosed with cancer and the tumor is found to have the genes, doctors may be able to provide drugs preventively, or at least have them ready for whenever the metastasis is detected.
The scientists believe the technique could be expanded to pinpoint genes involved in the spread of breast cancer to other organs or other types of cancer.
"We have already identified a set of genes that mediate metastasis to the bone," said Massague.
Cancer bomb zaps tumor cells in mice
Treatment could have the same effect in humans, scientists say
July 27, 2005
LONDON - A smart anti-cancer bomb that acts like a Trojan horse can penetrate deep into tumors where it explodes and destroys cancerous cells without harming healthy ones, scientists said on Wednesday.
Researchers at the Massachusetts Institute of Technology who devised the molecular size bomb tested it in mice with skin or lung cancer. Mice given the treatment lived more than three times longer than untreated rodents.
The scientists believe it could have the same effect in humans.
“We’re quite hopeful and optimistic that as we translate this into humans the results pan out as they have in animals,” Professor Ram Sasisekharan, of MIT’s Biological Engineering Division, said in an interview.
The smart bomb uses nanotechnology which manipulates materials on a molecular or atomic scale, to deliver chemotherapy drugs to destroy the tumor and anti-angiogenesis agents to block its blood supply.
After the bomb, which is like a balloon within a balloon, is injected into the bloodstream it travels to the tumor and burrows deep inside. The outer membrane then disintegrates and releases an anti-angiogenesis drug so the blood vessels feeding the tumor collapse.
Few side effects
The drug-packed nanocell trapped inside the tumor explodes unleashing the chemotherapy drug to kill the cancerous cells. No healthy cells are destroyed so debilitating side effects such as hair loss, vomiting, nausea and weight loss could be eliminated.
“If you don’t really shut the supply lines the tumor cells can escape and that is how they metastasize (spread). By killing the supply lines you are limiting the leaching of the chemotherapy agents to the healthy cells,” Sasisekharan said.
Breast cancer risk less when pregnant mom smoked
May 5, 2005
By Michelle Rizzo
NEW YORK (Reuters Health) - Women whose mothers smoked while they were pregnant have a reduced likelihood of developing breast cancer, according to a new study.
However, "This observation certainly does not suggest that smoking is beneficial," Dr. William C. Strohsnitter told Reuters Health. "The very small reduction in breast cancer would be offset by the large number of other diseases caused by cigarette smoking."
The reason for the finding may be connected to estrogen, which is linked to breast cancer risk.
"Clinical studies show that maternal cigarette smoking reduces pregnancy estrogen levels," Strohsnitter, of Tufts-New England Medical Center, Boston, and colleagues write in the medical journal Epidemiology. "Women prenatally exposed to maternal cigarette smoke may, therefore, have a lower breast cancer risk."
The team's report is based on an analysis of data from the National Cooperative DES Adenosis project, a follow-up study that examined the health outcomes in women exposed in the womb to diethylstilbestrol (DES), a drug later found to have harmful effects.
The study participant's mothers gave information about their smoking habits during pregnancy. The investigators then compared the rates of breast cancer among some 4000 women who were or were not exposed to maternal cigarette smoke before they were born.
After adjustment for other risk factors, women exposed in the womb to cigarette smoke had approximately half the breast cancer rate as those not exposed.
The association was more apparent among women whose mothers smoked no more than 15 cigarettes per day than among those whose mothers were heavier smokers. However, there were too few heavy smokers to precisely estimate a dose-response relationship.
Toddler terror? Maybe it's the tobacco
By David Steinkraus 7-20-06
Women are advised to avoid smoking during pregnancy to decrease the risks of stillbirth and low-birth weight, which is associated with later problems such as learning difficulties. But research is also suggesting that mothers who smoke during pregnancy may be causing misbehavior in their children with effects lasting long beyond childhood.
Previous studies have associated prenatal smoking with criminal behavior, in one case in people in their 30s. Now a new study by the University of Illinois at Chicago has found hints of misbehavior in children of a very young age. Nationally, at least 11 percent of women smoke during pregnancy.
Lauren Wakschlag, 48, was the lead author of the UIC study. She is a clinical psychologist and associate professor of psychiatry at the UIC College of Medicine's Institute for Juvenile Research. The study was published in the July/August issue of the journal Child Development.
Why don't you give me a sentence or three summarizing the paper that you did? "Well, about a decade ago we discovered a relationship between mothers we called smoking during pregnancy and the development of conduct disorder, antisocial behavior in older youth. Š So question for the field has been: Is it making a causal contribution, or is it just the type of women who smoke? "What we found (in the current study) was, indeed, we saw a very atypical pattern in two ways. One was, when we followed the babies over time between the first and second year of life, and we looked at behavior problems generally - or destructive behavior because the thing is that the period started the terrible twos so you expect some of these things - but what we saw was that for the nonexposed children those were mild behaviors, and they were relatively stable. But for the exposed children, they had higher levels right from the beginning and between 18 and 24 months those behaviors escalated in a very striking fashion.
"In fact, of the children at 24 months who had behaviors in the clinical range, 90 percent of them were exposed (to prenatal smoke).
Exposure to prenatal smoke was associated with greater incidences of stubborn defiance, aggression, and poor social skills but not with tantrums. "And that's important because those behaviors are associated with different brain regions, so it's a way for us to direct the next stage of studies in terms of looking at the underlying potential mechanisms that may be affecting the behavior."
So you've really pushed this association a little earlier in the age range? "A lot earlier because part of it was to figure out what to look at in these little kids.
"What we're seeing in babies we wouldn't call criminality or antisocial behavior; we would call it more like a vulnerability to developing those kinds of antisocial behaviors. Š Now I will also say that many children who show these problems early on do not go on to develop more serious antisocial behavior.
"If you have these vulnerabilities, often what happens is they may interact with other risks in your environment to determine whether you have these behaviors and they become a serious problem for you or not."
Which brings up another question. A previous study linked misbehavior to prenatal smoking only when children had a certain genetic profile. So what you were talking about, interacting with other factors, could be something like that? "Yes, and actually that's a really good question because in the beginning when this work started with those older youth studies, people were saying maybe it's just a marker for genetic risk - like, people who have a genetic risk for these kinds of psychiatric problems are more likely to smoke. But now people are moving to a much more complex way of thinking about it which is that it's not an either-or phenomenon but that the exposure may potentiate other kinds of risk."
"So the next level, the frontier, is sort of to be looking at the underlying neurobiologic mechanism.
"While we don't know it's causal, there is certainly very robust and consistent evidence that the effects of smoking during pregnancy may not end in the neonatal period.
"There are many kids whose mothers smoked during pregnancy who do not have these problems, and there are kids whose mothers do not smoke who do have these problems. And antisocial behavior Š is multiply determined. It's not any one thing usually.
"There's nothing specific you do if the child has these problems and they were exposed other than the standard kinds of interventions you would do for these problems more broadly."
With the publicity lately on secondhand smoke, I was curious whether the source makes a difference? "There's not evidence, really, for what we would call passive exposure during pregnancy - in other words you don't smoke but someone you live with does. The evidence is really for the direct exposure."
Any last thoughts? "I think it's very exciting, and ultimately I hope it will lead to prevention, to really effective prevention; we don't have to wait until serous problems emerge to try to alter that trajectory."
In Summary The question: If children have mothers who smoked during pregnancy, are they more likely to misbehave as toddlers? The study: Researchers looked at a group of about 93 white, working-class women because they are most likely to smoke during pregnancy. About half the group were smokers, half nonsmokers. In addition to questionnaires, researchers used blood tests to help determine how much women smoked, and observed children directly to gauge their behavior.
The result: Misbehavior was more prevalent at 18 and 24 months in children exposed to tobacco smoke prenatally.
What's next: The study hasn't proved that smoking causes misbehavior; other factors could still combine to give the same result. So scientists next will look at brain function and at whether certain genetic profiles are involved.Read
