Breast Cancer Risk Assessment

A new study reconfirms something often forgotten by women and sometimes even by doctors: just because breast cancer has not struck a family before does not mean family members are safe from the disease.

Researchers tracking more than 6,000 women for up to six years found that most cases of breast cancer occurred in those without a family history of the disease, although many of the women had other known risk factors that can help predict an individual woman's likelihood of developing the disease.

Breast cancer accounts for about a quarter of all cancers in women, with nearly 200,000 new cases of invasive breast cancer -- disease that has spread beyond the milk ducts or milk-making glands -- diagnosed in the U.S. every year.

"I have newly-diagnosed breast cancer patients ask me all the time how they could have developed the disease since they did not have a family history," researcher Dr. Lawrence Wickerham of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Allegheny Center, in Pittsburgh, told Reuters Health in an e-mail.

Prior studies have shown that more than 70 percent of primary care doctors ask women about their family histories, while less than half collect information on other known risk factors such as whether a woman's period began before age 12 - which raises risk - or whether she has given birth, which lowers risk.

Wickerham, along with lead researcher Angelina Sontag, of Eli Lilly and Company, and their colleagues analyzed the roles of various risk factors among 6,322 postmenopausal women who had participated in two large trials of osteoporosis medications. (Eli Lilly and Company, a maker of breast cancer treatments, also funded the current study.)

At the time of each trial, all of the women were under 86 years old and none had received a previous diagnosis of breast cancer.

The team used the Breast Cancer Risk Assessment Tool (http://www.cancer.gov/bcrisktool), an online questionnaire developed by NSABP and the National Cancer Institute, to go back in time and predict the odds that the women would develop invasive disease over the next five years.

The risk calculator incorporates age of first menstruation, current age, ethnicity, reproductive history, prior breast biopsies and family history. Its score, on a scale of zero to eight, represents a woman's five-year risk as a percentage.

Some 600 women in the study group -- approximately one in ten -- had a family history of breast cancer and nearly all of these met the predictive tool's definition of high risk: a score of 1.66 percent or above.

More than half of the remaining women without family histories of breast cancer also fit into the high-risk category, however.

A total of 92 women, or 1.5 percent of the study population, went on to develop invasive breast cancer over an average follow-up period of 4 to 6 years. As expected, the actual rate of breast cancers increased with the predicted risks, as well as in the presence of a family history.

Nevertheless, more of the total number of breast cancer cases ended up being reported in women with predictions below the high-risk cut-off or without a family history.

Close to half (40) of the women who developed the disease received a risk score below 1.66 percent, for example, and nearly two of every three (60) diagnosed women had been assigned risks between 1 and 2 percent and had no family history of breast cancer.

"The single largest risk factor for developing a breast cancer is being a woman and the second largest is being a women over 50," said Wickerham. "However, there are some women who are at greater than average risk, particularly those with a family history."

The most common known risk factors found in the study population were being at least 65 years old and beginning menstruation before the age of 12, report the researchers in the journal Menopause.

"Physicians and other health care providers should consider using methods beyond asking about family history to access breast cancer risk," added Wickerham, alluding to the Breast Cancer Risk Assessment Tool. "Such efforts can help better identify women at increased risk and can better focus screening and prevention strategies for them."

Second Hand Smoke

Around one in a hundred deaths worldwide is due to passive smoking, which kills an estimated 600,000 people a year, World Health Organization (WHO) researchers said on Friday.

In the first study to assess the global impact of second-hand smoke, WHO experts found that children are more heavily exposed to second-hand smoke than any other age-group, and around 165,000 of them a year die because of it.

"Two-thirds of these deaths occur in Africa and south Asia," the researchers, led by Annette Pruss-Ustun of the WHO in Geneva, wrote in their study.

Children's exposure to second-hand smoke is most likely to happen at home, and the double blow of infectious diseases and tobacco "seems to be a deadly combination for children in these regions," they said.

Commenting on the findings in the Lancet journal, Heather Wipfli and Jonathan Samet from the University of Southern California said policymakers try to motivate families to stop smoking in the home.

"In some countries, smokefree homes are becoming the norm, but far from universally," they wrote.

The WHO researchers looked at data from 192 countries for their study. To get comprehensive data from all 192, they had to go back to 2004. They used mathematical modeling to estimate deaths and the number of years lost of life in good health.

Worldwide, 40 percent of children, 33 percent of non-smoking men and 35 percent non-smoking women were exposed to second-hand smoke in 2004, they found.

This exposure was estimated to have caused 379,000 deaths from heart disease, 165,000 from lower respiratory infections, 36,900 from asthma and 21,400 from lung cancer.

For the full impact of smoking, these deaths should be added to the estimated 5.1 million deaths a year attributable to active tobacco use, the researchers said.

While deaths due to passive smoking in children were skewed toward poor and middle-income countries, deaths in adults were spread across countries at all income levels.

In Europe's high-income countries, only 71 child deaths occurred, while 35,388 deaths were in adults. Yet in the countries assessed in Africa, an estimated 43,375 deaths due to passive smoking were in children compared with 9,514 in adults.

Pruss-Ustun urged countries to enforce the WHO's Framework Convention on Tobacco Control, which includes higher tobacco taxes, plain packaging and advertising bans, among other steps.

"Policy-makers should bear in mind that enforcing complete smoke-free laws will probably substantially reduce the number of deaths attributable to exposure to second-hand smoke within the first year of its implementation, with accompanying reduction in costs of illness in social and health systems," she wrote.

Only 7.4 percent of the world population currently lives in jurisdictions with comprehensive smoke-free laws, and those laws are not always robustly enforced.

In places where smoke-free rules are adhered to, research shows that exposure to second hand smoke in high-risk places like bars and restaurants can be cut by 90 percent, and in general by 60 percent, the researchers said.

Studies also show such laws help to reduce the number of cigarettes smoked by smokers and lead to higher success rates in those trying to quit.

Great American Smokeout

2010 American Cancer Society Great American Smokeout Facts at a Glance

• This year, the Great American Smokeout will be held November 18.

• Quitting and avoiding tobacco products is one of the most important steps to creating a world with less cancer and more birthdays. It helps Americans stay well by reducing their risk of cancer.

• The Great American Smokeout is designed to motivate and empower smokers with personalized tools, tips, and support to help them quit for good.

• The Society hosted its first Great American Smokeout in 1976 as a way to inspire and encourage smokers to quit for one day.

• Smokeout does more than urge smokers to quit for a single day -- it encourages people to help create a world with less cancer and more birthdays by committing to making a long-term plan to quit for good and/or by supporting laws that help protect communities from tobacco.

• The American Cancer Society and its nonprofit, nonpartisan advocacy affiliate, the American Cancer Society Cancer Action NetworkSM (ACS CAN), have been successful in protecting the public from cigarettes and secondhand smoke:
• Today, nearly 75 percent of the United States population is covered by 100 percent smoke-free workplace and/or restaurant and/or bar laws, despite aggressive efforts by tobacco companies to defeat such laws.*
• Thirty-five states, the District of Columbia, the Northern Mariana Islands, and Puerto Rico now protect nonsmokers by prohibiting smoking in workplaces, and/or restaurants, and/or bars.*
• Forty-seven states and the District of Columbia have increased their cigarette taxes since 2000.*

• In 2007, 39.8 percent (13.4 million) of adult current everyday smokers had stopped smoking for at least one day during the preceding 12 months because they were trying to quit. **

• Tobacco use remains the single largest preventable cause of disease and premature death in the United States.*

New Cancer Drug Shows Promise

An experimental cancer drug is proving effective in treating the lung cancers of some patients whose tumors carry a certain genetic mutation, new studies show.

Because the mutation can be present in other forms of cancer -- including a rare form of sarcoma (cancer of the soft tissue), childhood neuroblastoma (brain tumor), as well as some lymphomas, breast and colon cancers -- researchers say they are hopeful the drug, crizotinib, will prove effective in treating those cancers as well.

In one study, researchers identified 82 patients from among 1,500 patients with non-small-cell lung cancer, the most common type of lung malignancy, whose tumors had a mutation in the anaplastic lymphoma kinase (ALK) gene.

Crizotinib targets the ALK "driver kinase," or protein, blocking its activity and preventing the tumor from growing, explained study co-author Dr. Geoffrey Shapiro, director of the Early Drug Development Center and associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston.

"The cancer cell is actually addicted to the activity of the protein for its growth and survival," Shapiro said. "It's totally dependent on it. The idea is that blocking that protein can kill the cancer cell."

In 46 patients taking crizotinib, the tumor shrunk by more than 30 percent during an average of six months of taking the drug. In 27 patients, crizotinib halted growth of the tumor, while in one patient the tumor disappeared.

The drug also had few side effects, Shapiro said. The most common was mild gastrointestinal symptoms.

"These are very positive results in lung cancer patients who had received other treatments that didn't work or worked only briefly," Shapiro said. "The bottom line is that there was a 72 percent chance the tumor would shrink or remain stable for at least six months."

The study is published in the Oct. 28 issue of the New England Journal of Medicine.

In recent years, researchers have started to think of lung cancer less as a single disease and more as a group of diseases that rely on specific genetic mutations called "driver kinases," or proteins that enable the tumor cells to proliferate.

That has led some researchers to focus on developing drugs that target those specific abnormalities. "Being able to inhibit those kinases and disrupt their signaling is evolving into a very successful approach," Shapiro said.

The good news is that drugs such as crizotinib seem to work well in patients with the mutation, noted Dr. Roman Perez-Soler, chairman of the department of oncology at Montefiore Medical Center and professor of medicine and molecular pharmacology at the Albert Einstein College of Medicine in New York City. But the bad news is that it means that patients who don't have the specific mutation won't be helped.

Only an estimated 2 percent to 7 percent of non-small-cell lung cancers have the ALK mutation, according to the study.

"This is great news for people with this type of tumor," Perez-Soler said. "Researchers have identified a group of patients, unfortunately a small group, who because of a very specific genetic abnormality are extremely sensitive to these targeted treatments and as a result of that can benefit from this drug without toxicity. It's very encouraging."

In a second study in the same journal, crizotinib was effective in a 44-year-old man with inflammatory myofibroblastic tumor, a rare form of sarcoma, which is also driven by the ALK abnormality, said Shapiro, who was senior author of that paper.

Still, there are caveats. Over time, tumors can adapt to such targeted therapy, eventually rendering it ineffective, experts said. In fact, a third study in the same journal identified ways in which lung cancers had already started to mutate and overcome crizotinib.

Moreover, while drugs targeting a specific tumor genotype are promising, there could be so many different genotypes that it would be impractical to come up with drugs targeting all of them, Perez-Soler said. Still other tumors might be fueled by multiple abnormalities.

"Many cancers may be much more complicated," he said. "And every tumor is different. Each one has a number of sophisticated ways to overcome interventions to block growth, and some may be better prepared than others to do that. That is why you see heterogeneity in the response to the drug. There is no such thing as identical twins when we talk about tumors."

Researchers are currently enrolling patients for a larger, Phase III clinical trial of crizotinib, Shapiro said. The study was funded by Pfizer, which is developing crizotinib for clinical application, and by grants from the U.S. National Cancer Institute, among others.

Lung cancer remains one of the most deadly cancers and new treatments are desperately needed, the researchers said. "Advanced lung cancer still remains a very lethal disease," Shapiro said. "It's the biggest cancer killer of both men and women in the U.S. and worldwide, and the unmet clinical need is extreme."

NASA Imaging Technology Helps Fight Breast Cancer

The same software used by NASA scientists to determine the depths of lakes from space could also be used by doctors to detect changes in breast density during mammograms.

The imaging technology was approved in July by the U.S. Food and Drug Administration, under the name MED-SEG, for use in medical reports, though the software can't be used for diagnosis because clinical tests haven't been conducted yet.

A big problem with mammography is that it's hard to detect cancers in a woman's breasts if the tissue is too dense, said Dr. Molly Brewer, a professor of gynecologic oncology at the University of Connecticut Health Center. That could lead to missed opportunities to find breast cancer early.

"What happens when a radiologist reads a mammogram, CT scan or an MRI, is they look at differences in density, but that's subject to the human eye," Brewer said at a news conference today. "That's where differences can occur – we may not see with our eyes what a computer can see."

The MED-SEG could reduce the importance of subjectivity in reading mammograms, and allow doctors to get clearer results from an imaging test. The software may also fill a void between mammograms, which don't always detect changes in density, and magnetic resonance imaging tests (MRIs), which are more sensitive but also expensive, and can falsely reveal problems that aren't really there, Brewer said.

Accurately measuring breast density is important because previous research has found that among women with early breast cancer, those with the highest breast density are at the highest risk for cancer recurrence.

And mammograms currently miss up to 20 percent of breast cancers. Doctors have a harder time diagnosing women with dense breast tissue because the tissue looks similar to tumors in mammograms, according to the National Cancer Institute.

Brewer is working with Bartron Medical Imaging Inc., the owner of MED-SEG, to develop clinical trials to test the software in doctors' offices. The trials are set to start within the next six to eight months.

The software works because it doesn't look only at an image's individual pixels, which don't provide much information or context by themselves, said developer James C. Tilton, a computer engineer at NASA’s Goddard Space Flight Center in Maryland, who developed the software. Instead, it groups pixels based on their level of detail, and distinguishes hard-to-see details in the image, he said.

"I was surprised that something I developed for a large-scale earth science study could be applied effectively on such a small scale," Tilton said.

For example, in a satellite image of the Earth, all lakes would appear blue and all land would appear green. But in an image using the software, shallow lakes would have a different shade of blue than deeper lakes, he said.

The same goes for images of breast cells. Without the software, a cell is hard to distinguish from its background. But the software enhances the activity happening in the cell, making it easier to see fine detail, Tilton said.

Number 1 in Research

The American Cancer Society is #1 in research funding besides the federal government!

Your support of Relay For Life has allowed the American Cancer Society to be involved in nearly every major breast cancer research breakthrough of the last century, including:

* Funding research into breast-conserving surgery, using lumpectomy plus radiation for treatment
* Establishing mammography as the gold standard to find breast cancer early
* Discovering lifesaving treatments such as Herceptin and Tamoxifen
* Discovering genes for inherited breast and colon cancer
* Confirming the knowledge that genetics, diet, lack of exercise, and alcohol abuse can increase a person's cancer risk
* Discovering cancer-causing oncogenes and tumor-suppressor genes

October - Breast Cancer Awareness Month

The American Cancer Society recommends the following guidelines for finding breast cancer early in women without symptoms:

Mammogram: Women age 40 and older should have a mammogram every year and should continue to do so for as long as they are in good health. While mammograms can miss some cancers, they are still a very good way to find breast cancer.

Clinical breast exam: Women in their 20s and 30s should have a clinical breast exam (CBE) as part of a regular exam by a health expert, preferably every 3 years. After age 40, women should have a breast exam by a health expert every year. It might be a good idea to have the CBE shortly before the mammogram. You can use the exam to learn what your own breasts look and feel like.

Breast self-exam (BSE): BSE is an option for women starting in their 20s. Women should be told about the benefits and limitations of BSE. Women should report any changes in how their breasts look or feel to a doctor or nurse right away.

If you decide to do BSE, you should have your doctor or nurse check your method to make sure you are doing it right. If you do BSE on a regular basis, you get to know how your breasts normally look and feel. Then you can more easily notice changes. But it's OK not to do BSE or not do it on a fixed schedule.

The most important thing is to see a doctor right away if you notice any of these changes:

* A lump or swelling
* Skin irritation or dimpling
* Nipple pain or the nipple turning inward
* Redness or scaliness of the nipple or breast skin
* A discharge other than breast milk

But remember that most of the time these breast changes are not cancer.

Women at high risk: Women with a higher risk of breast cancer should talk with a doctor about the best early detection plan for them. This might mean starting mammograms when they are younger, having extra screening tests, or having more frequent exams. There are charts called risk assessment tools that a doctor can use to figure out whether you are at high risk.