Montclair Breast Center

The Wall Street Journal, July 1, 2008

New Surgery Eases the Toll Of Breast Cancer

Surgeons are increasingly offering an added benefit to their breast-cancer patients: removing the tumor and cosmetically repairing the breast at the same time.

Women with breast cancer traditionally would see a cancer surgeon to have the diseased tissue removed and later see a plastic surgeon for reconstruction. Now, more cancer surgeons are getting trained in cosmetic techniques that preserve or restore a breast's shape or appearance. This emerging field of "oncoplastic surgery" could allow a patient to minimize the number of times she must go under the knife.

The shift comes as traditional plastic surgeons turn increasingly to purely cosmetic procedures, which pay more. Indeed, the number of breast-reconstruction surgeries declined 29% to 57,100 last year from 2000, a development the American Society of Plastic Surgeons attributes in part to poor insurance reimbursement for these procedures.

Breast cancer strikes one out of eight American women at some time in their lives. Making plans for breast reconstruction at the same time as cancer surgery can speed a woman on the path of psychological, as well as physical, recovery. And by combining procedures to reduce the number of operations, it also reduces the risk of complications from successive surgeries.

The combination of cancer surgery with cosmetic techniques is aimed mainly at women with early-stage cancer getting a lumpectomy, a procedure that removes cancerous tissue but leaves the rest of the breast. Oncoplastic surgery also can sometimes benefit patients who need a mastectomy, or total breast removal, by helping to prepare their bodies for subsequent reconstruction.

"There is a growing awareness that we haven't done as good a job as we should" in offering aesthetic options to breast-cancer patients, says Pat Whitworth, director of the Nashville Breast Center in Nashville, Tenn.

In a typical lumpectomy, also called a partial mastectomy, the surgeon makes an incision, scoops out the cancerous tissue and then closes the opening. That can often leave the breast with a disfiguring dent. In oncoplastic surgery, by contrast, a wedge is removed and tissue under the skin is then pulled together to close the defect. That can leave the breast looking smaller, but otherwise normal. Sometimes an oncoplastic approach may be taken by two surgeons teaming up to do cancer removal and repair in the same operation.

"What we're talking about for the most part is how to do a nice lumpectomy," rather than relying on breast reconstruction that uses artificial implants or tissue transplants, says Benjamin Anderson, director of the University of Washington's breast clinic in Seattle.

Sandy Masson, a 48-year-old nurse and director of women's services at Hoag Hospital in Newport Beach, Calif., was diagnosed with breast cancer in April. The first surgeon she consulted recommended a mastectomy, because she had two lumps in different parts of her breast, and she was set to go ahead with it. Ms. Masson, a mother of two young children, says her only thought was: "I want to live; I don't care what I look like."

At the urging of colleagues, Ms. Masson then consulted Melvin Silverstein, an oncoplastic surgeon who had recently moved his practice to Hoag. He told her she could avoid a mastectomy without incurring any increased risk to her survival. Dr. Silverstein says he removed a crescent-shaped chunk of tissue that got both cancerous lumps but spared a substantial portion of the breast. In the same operation, he reduced the size of her other breast to give her a symmetrical appearance.

A week later, Ms. Masson was back to work and is now undergoing chemotherapy. "I'm normal now and not deformed," Ms. Masson said recently, lifting her blouse and bra to display Dr. Silverstein's handiwork.

The number of surgeons using oncoplastic techniques is small but growing, says Diana Rowden, a breast-cancer survivor and vice president of health sciences at Susan G. Komen for the Cure, a Dallas-based advocacy group. There is no professional certification for oncoplastic surgeons, so patients should inquire about a practitioner's training and experience.

The American Society of Breast Surgeons since 2005 has sponsored introductory oncoplastic courses at its annual meeting. In December, the American Society of Breast Disease, a group that includes radiologists and oncologists, held its first School for Oncoplastic Surgery in Texas. The three-day course, to be repeated this year, included a session at the cadaver laboratory at Baylor Medical Center at Frisco, where the surgeons got to practice some techniques. Practitioners say they don't make more money from oncoplastic surgery than from regular cancer surgery, and say the attraction is mainly wanting to do a better job for their patients.

Some cancer surgeons say they are seeking oncoplastic training because of a shortage of reconstructive surgeons, a growing problem especially in rural areas and midsize towns. Plastic surgeons are "bailing out" because "they get paid $1,000 for reconstruction when instead they could do four breast augmentations at $5,000 a pop or more," says Michael Cross, a breast surgeon in Fayetteville, Ark. Reconstructive surgeries also often take more time to perform than purely cosmetic procedures.

"The vast majority of plastic surgeons still do both reconstructive and cosmetic surgery," says Michael McGuire, a spokesman for the American Society of Plastic Surgeons. Still, he blames the decline in reconstructive surgery in recent years on poor insurance reimbursement that "is part of the greater health-care crisis in this country." Federal and state laws require insurance companies to cover breast reconstruction, but the laws don't set payment rates.

Dr. McGuire says he welcomes efforts by cancer surgeons to learn what plastic surgeons can do, but he is skeptical of oncoplastic courses. "To think a surgeon can learn how to do this in a weekend course is unwise," he says. Cancer surgeons say that some techniques aren't difficult and can be quickly adopted. They agree that more intensive training is needed for more complicated procedures, such as reconstruction using artificial implants.

Stephania Timothy, a general surgeon in Wenatchee, Wash., says that after attending a daylong course in New York recently, she was able to start using simple incision techniques that give patients better cosmetic results. She says she plans to improve her skills by practicing at the University of Washington's cadaver laboratory and by pursuing more training.

The Mary Kay Ash Charitable Foundation announced Monday that it will fund a small fellowship program "to train breast surgeons in the emerging field of oncoplastic surgery." The program will be led by Gail Lebovic, a cancer surgeon at the Cooper Clinic in Dallas, who has received specialized training in reconstructive and plastic surgery.

Tanya Elmer says that after she was diagnosed with breast cancer two years ago, she interviewed surgeons who told her they would "get rid of the cancer and then 'you can go to another doctor'" for reconstruction. At the urging of a friend, the 54-year-old homemaker in Flower Mound, Texas, went to see Dr. Lebovic.

Ms. Elmer says her mind was eased when Dr. Lebovic explained how she would both perform the surgery and repair the breast. Ms. Elmer says the advance planning for reconstruction enabled her to complete the treatments after two surgeries, rather than three.

Before Surgery

Some questions for a cancer surgeon:
-- Do you specialize in breast surgery?
-- Are you familiar with oncoplastic surgical techniques?
-- How do those techniques apply to my case?
-- Do you ever do a lumpectomy with a breast reduction at the same time?

The Wall Street Journal, June 24, 2008

When a Mammogram Isn't Enough --- For Higher-Risk Women, the Addition of MRI or Sonogram May Improve Detection; a Problem With False Positives

By Anna Wilde Mathews

c) 2008, Dow Jones & Company, Inc.)

Mary Walls thought she was home-free after annual mammograms found no recurrence of the breast cancer she'd suffered in 1996. Then last fall she also got an ultrasound screening, which showed two questionable areas in her right breast.

After a biopsy confirmed that the two spots were malignancies, the Matteson, Ill., human-resources consultant got a lumpectomy, chemotherapy and radiation. "I don't think I'll ever trust just mammography by itself again," says Ms. Walls, 62, who received the ultrasound after deciding to participate in a research study her doctor was helping to conduct.
For many years, women worried about breast cancer have been given a simple prescription: annual mammograms, or X-rays of the breasts, typically starting at age 40. Now, doctors are increasingly advising some women who may be at higher risk for the disease to consider supplementing a mammogram with other, potentially more sensitive tests.
For those women whose family background, genetics or other factors signal a high level of concern, a growing number of physicians are suggesting magnetic resonance imaging, or MRI, which is typically the most sensitive form of screening. Some doctors are also recommending ultrasound, the sound-wave technology often used during pregnancy to view a fetus. Ultrasound can cost $100 or less, compared with $1,000 or more for an MRI. But ultrasound also is less sensitive than an MRI. Health insurers say they generally pay for ultrasound screening, but guarantee coverage of MRI screening only for women at high risk.

The heightened interest in additional screening follows new guidelines issued by the American Cancer Society last year. The cancer society recommended annual MRIs, in addition to mammograms, for women with certain genetic mutations tied to breast cancer and those whose family history signaled a significantly elevated lifetime danger of the disease, among other high-risk categories.

Backing the recommendation were a series of studies that showed an MRI could detect cancers missed by mammography. One study published in 2004 in the New England Journal of Medicine found that in high-risk women, MRIs detected 32 out of 45 breast cancers, while mammograms picked up 18, including some missed by the MRI screening. The two types of screening, plus physical exams, together found 41 of the cancers. The cancer society hasn't issued any recommendations regarding ultrasound screening, but says it continues to accumulate research data. One downside: the risk that MRI and ultrasound screenings can produce many false positives, creating needless anxiety in some patients.

After the cancer society's guidelines came out, Jerry Gehl, medical director of the St. Vincent Breast Center in Little Rock, Ark., started routinely recommending an MRI to high-risk patients, in addition to mammograms. In general, though, he doesn't urge patients to get an MRI if they face only a somewhat-elevated risk. "You have to draw that line somewhere," he says.

Stacy Adams, 36, got a breast-screening MRI for the first time in April at Dr. Gehl's suggestion after also getting a mammogram. Ms. Adams, a receptionist at a radiology clinic, says her mother was diagnosed with breast cancer at 31, and her grandmother was similarly diagnosed at 35. Ms. Adams says her tests showed there were no malignancies, and she plans to keep getting both screenings. "I'm just terrified I'm going to miss something," she says.

The American Cancer Society, in its 2007 guidelines, also identified a group of women at an above-average risk of developing breast cancer and for whom MRI might be helpful. But the society concluded there wasn't enough evidence to recommend for or against the scans. This group included breast-cancer survivors and women with dense breast tissue. Dense breasts, which are more common in younger women, are harder to read with a mammogram. Fatty tissue provides clearer contrasts.

"It's not very reassuring to hear 'your mammogram is normal, but it's only because we can't see anything at all,'" says Robert Smith, director of cancer screening at the cancer society. For women at average risk of breast cancer, the cancer society's guidelines opposed MRI as part of routine screening.

The cancer society also says that women can be separated into different screening-recommendation categories using computerized risk models that focus mainly on family history. Those with a lifetime breast-cancer risk of around 20% or more should supplement annual mammograms with MRI screenings, while those with a 15% to 20% risk are in the middle group, and women with a lifetime risk of less than 15% can stick with just the annual mammograms. More information is available at http://CAonline.AmCancerSoc.org. Search for "MRI screening."

Major private insurers Aetna Inc., WellPoint Inc. and Cigna Corp. say they pay for annual MRI screening in women at high risk of breast cancer, typically using criteria close to those of the cancer society. For women who fall short of high risk, but who still have a somewhat elevated chance of developing breast cancer in their lifetimes, insurers may not always pay. "Our policies provide benefits in situations in which there is adequate evidence to make a specific recommendation," says Bob McDonough, Aetna's head of clinical policy research and development.

For ultrasound screening, Cigna doesn't require prior authorization, so "it's at the discretion of the physician," says Douglas Hadley, director of the company's coverage policy unit. Dr. McDonough of Aetna says the insurer is for the moment "simply covering [ultrasound] without scrutinizing its use." WellPoint says it also doesn't require prior authorization for breast ultrasound screening.

Medicare covers mammograms, but the federal insurance plan for older people won't pay for ultrasound or MRI as part of routine screening. The program can pay for the exams if a doctor feels they are medically necessary, a plan spokesman says.

A study published in May in JAMA, the journal of the American Medical Association, highlighted the use of ultrasound as a supplement to mammograms. The study, conducted by American College of Radiology researchers, looked at women at a somewhat-elevated level of risk. It found that of 40 women diagnosed with breast cancer, mammograms raised red flags for 20, while mammography plus ultrasound detected 31.

But the study also highlighted a downside of ultrasound -- it generated many false positive readings. MRI screenings also carry this risk. Though the false alarms may result simply in extra time and stress pursuing additional scans, some women also get unnecessary biopsies. Often, these involve little more than a needle stuck into the breast, with no scarring or long-term effects.

But biopsies can also be quite invasive. Sharon Nelson, 54, who had cancer in her right breast nearly a decade ago, had a scare when an MRI in 2003 picked up potential trouble spots in both breasts. Alarmed that her disease may have returned, and worried about her health while her two daughters were still young, she got biopsies that involved removal of significant tissue. There was no cancer, but she was left with a visible indentation in her healthy left breast. "It's hard to have a surgery that wasn't necessary," says Ms. Nelson, a nurse at a breast-health nonprofit center in Arcata, Calif.
Medical practitioners are divided about the proper role of ultrasound in breast-cancer screening. Wendie Berg, a radiologist at a clinic in Lutherville, Md., who was the lead author of the study published in JAMA, says she recommends ultrasound screening to some women who don't have evidence of very high risk that would justify an MRI. "It is a judgment call. The denser the breast, the more difficult the mammogram is to read, the more likely I am to recommend an ultrasound," she says.

But Constance Lehman, a University of Washington professor of radiology who led a study published last year in the New England Journal on MRI screening, says she never advises ultrasound for patients. "We find it ineffective as a screening tool," she says. "It's not even in the same ballpark" as an MRI.

Extra Screening

The American Cancer Society says some women may need more than a mammogram to screen for breast cancer.

Women at high risk should also get an annual MRI.

For women at moderate risk, there isn't enough evidence for or against MRI screening.

Annual mammograms are still the staple prescription for women at average risk.

The Wall Street Journal, February 27, 2008

In a surprise decision, the Food and Drug Administration played against type and gave approval for Avastin as a treatment for metastatic breast cancer. It was the right option for terminally ill women, who will gain another weapon against a disease that kills about 40,000 every year.

In clinical trials, Genentech's biologic drug was shown to control the growth and spread of tumors, doubling the amount of time before illness worsened. That translates into an improvement in quality of life, and the results were corroborated by further studies.

Avastin shouldn't have been controversial. But an FDA panel ruled that "progression-free survival" was not sufficient, because the agency's usual acid test for anticancer agents is extending life overall. Such an analysis overlooks the real benefits to women in the months they have left. But as late as last week, it looked as though approval would be delayed or rejected outright.

The "accelerated approval" granted to Avastin is contingent on follow-up trials, and Avastin could be pulled from the market if future research fails to demonstrate that treatment prolongs life. In an interview with us on Monday, oncology drugs chief Richard Padzur said that the FDA was "not demanding" a survival advantage but would consider it a factor. In 2005, the lung cancer drug Iressa was approved and then withdrawn under similar conditions, and the danger is that history will repeat itself.

As for the notion that the decision portends a shift in the way the FDA evaluates cancer drugs, Dr. Padzur assured us that it is "not a new step in our regulatory decision making." He emphasized that prolonging life was still the FDA's primary criterion, and noted that Avastin was green-lighted because its quality-of-life benefits were "statistically robust." Yet the narrowness with which the FDA balances risk and reward was the reason Avastin was contentious -- especially Dr. Padzur's statistical models.

FDA evaluation methods insist on large average effects and simplistic mortality rates. Only about 10% of patients responded to Iressa, for instance, and could be identified by genetic tests; but these targeted results didn't mesh with the arbitrary FDA approach. Other innovative medicines like Provenge (for prostrate cancer) and Junovan (for pediatric bone cancer) are pointlessly blocked by Dr. Padzur's division, and the risk is that Avastin still could be too, whatever its current reprieve.

The finality of life-and-death decisions makes the approval of such drugs fundamentally a moral issue. Avastin may have slid beneath the wire, but the FDA hasn't changed its morally indefensible standard, and further drug approvals are still subject to the whims of a bureaucracy that puts statistical models above the choices of dying patients.

The Wall Street Journal, December 10, 2007

Scientists Link Gene's Role in Breast Cancer

Associated Press
10 December 2007
The Wall Street Journal
(Copyright (c) 2007, Dow Jones & Company, Inc.)

Researchers say they've discovered a major reason why women who inherit a mutated version of the gene BRCA1 run a high risk of breast cancer, and that finding might aid the search for new treatments.

A second gene, called PTEN, plays a key role, scientists said in a study released yesterday.

Scientists have long known that BRCA1 normally repairs damage to other genes. So if it is crippled by mutations, the unrepaired damage could be expected to lead to cancer. But the specifics of that story have been murky.

The new study fingers PTEN, which normally acts as a brake on cancer. The researchers found evidence that in breast cancers associated with a BRCA1 mutation, PTEN is often broken and doesn't get repaired. That sets off a chemical cascade that leads to malignancy.

This is "probably a major way" that defects in BRCA1 can produce breast cancer, said Ramon Parsons of Columbia University, who reports the work with colleagues on the Web site of Nature Genetics.

PTEN was discovered about 10 years ago, and scientists know a lot about it and the chemical pathway that gets activated when PTEN is disabled, he said. Drug companies have been testing drugs in animals that seek to treat tumors by interrupting that cascade, and they have gotten some encouraging results, he said.

Breast cancers associated with the BRCA1 gene are generally aggressive and have a poor prognosis. BRCA1 and its cousin BRCA2 account for less than 15% of all breast cancers.

The Wall Street Journal, May 30, 2006

Mammograms: Digital vs. Film --- Doctors Worry That Women Are Delaying Test to Wait For Still-Scarce Technology

By DAVID ARMSTRONG
1276 words
30 May 2006

FOR THE 23 million U.S. women who get mammograms each year, there is an increasingly urgent question: digital or film?

Interest is growing in the digital version of the breast-cancer screening test, driven in part by a study last fall in the New England Journal of Medicine that said digital was better for some women. The findings quickly became a marketing tool for makers of digital-mammography machines and hospitals that have them. Sales of the machines have been rising, with one major manufacturer citing digital equipment as the driving force behind record second-quarter revenue.

But some hospitals and doctors are concerned that the advantages of digital are being overestimated and may be causing women to delay getting a mammogram until digital machines arrive in their area. Still only about 11% of the 8,800 U.S. mammography facilities are estimated to have digital.

The advice from doctors: Don't wait, especially if you are in one of the groups for whom digital has no demonstrated advantages. The study found that digital was better at detecting cancer only for premenopausal women, those under 50 years old, or those who have dense breasts. The majority of women who get mammograms are over 50, and looking at the 40,000 women in the study as a whole, the new technology was found to be no better than film overall.

Past research on the use of digital-mammography machines, which were first approved by the federal Food and Drug Administration in 2000, showed no overall benefit compared with film, though the studies may have been too small to identify benefits in subgroups.

"One thing that concerns radiologists is that women will think film isn't good," says Kathleen Brant, chairwoman of the breast imaging and intervention division at the Mayo Clinic in Rochester, Minn. "Our position is it is best to have a mammogram of any kind rather than no mammogram."

Dr. Brant says a lot more women are asking their doctors about digital. At the Mayo Clinic, which has both kinds of machines, women who fall into one of the categories shown to benefit from digital are generally referred for a digital exam, she says. But most women still receive film mammograms at the facility.

The Michigan Cancer Consortium -- a network of hospitals, insurers and private and public health groups -- issued a position paper on digital mammography last month in response to the large number of questions it was getting from patients and hospitals. The consortium advised that "although digital mammography can detect cancers that might be missed by film mammography," that isn't true for all women. The organization recommended that when both types of screening are available, the decision be tailored to each woman.

The FDA may soon make it easier for digital-mammography makers to bring new machines to the market. An advisory committee voted last week to put digital-mammography machines in a class where manufacturers must prove only that their equipment is substantially similar to products already on the market. Currently, manufacturers often have to conduct costly clinical trials testing safety and efficacy before gaining approval for the machines. The committee action still needs agency approval.

For hospitals and physicians, there is another reason to favor digital mammography. The insurance reimbursement for digital screening is much higher. The national average for Medicare reimbursement (which many insurance companies base their own rates on) is $85.65 for film mammography and $135.29 for digital. For years, mammography has been a money loser for many hospitals. While the digital machines are as much as four times as expensive to purchase, over time the higher reimbursement rates could produce more-profitable returns.

Many breast-cancer specialists believe it is only a matter of time before digital mammography is the standard screening tool. That is largely because all of radiology is going digital, from magnetic-resonance-imaging scanners to CT machines. One major maker of digital-mammography equipment, Hologic Inc. of Bedford, Mass., last month reported a 46% increase in revenue for the second-quarter compared with the year prior, citing strong sales of its digital-mammography equipment. Other big makers of the digital equipment include Siemens AG and General Electric Co.

Both digital and film mammograms take X-ray images of the breast. The traditional method uses film to capture and display the image. Digital mammography is filmless, and captures the X-ray as an electronic image. The images themselves are similar, but one potential advantage of digital is that it allows radiologists more leeway to magnify or enhance the image. Some radiology centers say digital equipment delivers less radiation. But most experts note that the level of radiation in film mammography is already extremely low.

Digital images are also easier to store, and can be quickly shared among specialists at different locations. Storing large numbers of film images of mammograms can be expensive. As a result, "ultimately the cost will be less" with digital, says Max Wicha, the director of the University of Michigan Comprehensive Cancer Center.

The issue of whether digital mammograms are actually better for detecting cancer than traditional film X-rays remains a matter of debate. An editorial accompanying the New England Journal of Medicine study concluded the "advantage offered by digital mammography appears to be limited to a minority of women who undergo screening, since most women who get a mammogram are over 50 and post-menopausal."

The U.S. Preventive Services Task Force, a government appointed panel of health experts, recommends women over 40 undergo a mammogram at least every other year. The task force found the screening benefit was greatest for women aged 50 to 69. A spokeswoman says the task force is scheduled to release an update of its breast-cancer screening recommendations next year.

The American College of Radiology has no position on digital vs. film, and officials there say it is more important that women get at least some form of mammography regularly.

The New England journal study, which was funded by the National Cancer Institute, didn't look at whether or not digital screening resulted in fewer women dying from cancer, notes Mark Ebell, a physician and researcher at Michigan State University in East Lansing, Mich., who is an expert on evidence-based medicine. "The benefit may be so small that is not cost-effective," he says. The study researchers say they are now conducting a cost-effectiveness analysis of the digital technology.

Dr. Ebell worries the higher cost of digital mammography will make the screening unaffordable for women without health insurance.

"There is no reason to get any more of these [digital] units because they haven't been shown to have a benefit for the overall population," says Carolina Hinestrosa, an executive vice president for National Breast Cancer Coalition, a nonprofit group in Washington that lobbies for more federal funding of breast-cancer research. "From a public-health standpoint, we don't think it is a wise thing to do."

The Wall Street Journal, May 30, 2006

HEALTH JOURNAL
The Case for Soccer: How Exercise, Diet May Cut Girls' Later Breast-Cancer Risk

By TARA PARKER-POPE

MOST WOMEN start worrying about breast cancer in their 40s, a time when doctors start to recommend regular mammograms.

But a growing body of evidence shows that a woman's risk for breast cancer may be determined far earlier in life. Cellular changes that can lead to cancer likely begin in childhood when breast tissue is just beginning to develop.

So while strategies like diet, exercise and -- for high-risk women -- prevention drugs like Tamoxifen may help stave off breast cancer in midlife, scientists are also beginning to look at prevention efforts for young girls. What's increasingly clear is that the health decisions parents make for their daughter in preschool, adolescence and the late teen years have the potential to dramatically alter her risk for breast cancer as she becomes a woman.

To understand why, it helps to know how breast tissue develops. During early childhood, breast tissue is mostly dormant until the pituitary gland and ovaries produce enough hormones, including estrogen, to accelerate breast growth. This happens when a girl starts menstruating and continues for several years. This stretch of rapid cell growth appears to be a particularly vulnerable one for the breast, and may be the time when the first cellular changes that can lead to breast cancer are most likely to occur. As a result, health behaviors at a young age may have a particularly big impact on a girl's lifetime risk, and girls with a high family risk for breast cancer may reap even greater benefits.

Here are some theories on what can parents do to lower their daughters' risk.

-- Encourage exercise at a young age. Exercise early in life appears to lower a girl's hormone levels, and potentially delay the onset of her first period. The average age of first period today is about 12, but some girls start periods as early as nine or 10. Girls who don't get their periods until the age of 13 or 14 have a lower lifetime risk for breast cancer.

Exercise before puberty lowers body fat and also damps down hormone production by the pituitary gland, keeping hormone levels low longer and thereby delaying menstruation. "It's important to start things young," says Anne McTiernan, director of the Prevention Center at the Fred Hutchinson Cancer Center in Seattle and author of the book "Breast Fitness." Dr. McTiernan suggests an hour of daily exercise for girls, including recess and gym class.

The benefit of exercise continues into the teen years even after a girl starts her period, possibly by lowering body fat, which produces estrogen. Some of the most compelling evidence that athleticism in the late teen years influences breast-cancer risk comes from studies by Harvard researchers looking at breast-cancer risk among 5,400 former college athletes and nonathletes. The college athletes, the vast majority of whom also took part in high-school sports, had a dramatically lower risk for breast cancer. Among women of all ages, breast-cancer risk was 40% lower among former college athletes.

To help kids stay active, try signing them up for the same sports and lessons their friends are taking. A Purdue University study of sixth graders found that the most physically active kids were those who had a close friend taking part in the same activity. Parents who exercise are also more likely to have kids who exercise.

-- Limit Junk Food. Some research suggests that diet early in life and into adolescence can influence breast-cancer risk. In February, a Harvard study suggested a child's preschool diet could affect breast-cancer risk. Women who frequently ate french fries in preschool had a 27% higher risk for breast cancer as adults.

Modest reductions in fat intake during puberty can lower levels of hormones in a girl's body. Girls who eat diets higher in fiber appear to get their first period later. Some evidence suggests that increasing soy in the teen diet can also lower long-term breast risk. Even though the data on adolescent diet and breast-cancer risk are mixed, it makes sense to encourage girls to eat fruits and vegetables and avoid unhealthy fats.

"It's not going to hurt girls to have these foods in their diet," says Sally Scroggs, senior health education specialist at University of Texas M.D. Anderson Cancer Center, Houston.

-- Talk about alcohol. It's already clear that women who drink more than one serving of alcohol a day have a higher risk for breast cancer. But some data suggest that the age at which a woman starts drinking influences risk. Teens and young women who consume high levels of alcohol before the age of 25 may be at higher risk for breast cancer. When talking to kids about drinking, parents should tell daughters that lower breast-cancer risk is among the many potential benefits of responsible drinking.

-- Discuss birth-control options. It's a controversial notion, but the use of birth-control pills during the teen years may also increase risk for breast cancer. An analysis of more than 150,000 women around the world showed women who started using oral contraceptives as teenagers were at higher risk for breast cancer than women who started the pill later in life. The increased risk is slight, so the tradeoff for preventing an unwanted teen pregnancy may be worth it to many parents. But teenagers also need to be concerned about sexually transmitted diseases, so for sexually active girls, condoms may be a better choice.

The bottom line is that it's never too early to start thinking about a girl's long-term breast health. To get a better sense of your overall risk for breast cancer, take the quiz at www.yourdiseaserisk.com .

The Wall Street Journal, May 9, 2006

HEALTH JOURNAL
The Breast Cancer Link: Study Offers Insight Into Long-Term Estrogen Use

By TARA PARKER-POPE

NEW DATA on estrogen show the risk of breast cancer is lower than previously believed and begin to answer questions about how long women can safely use the hormone.

The research, from Harvard University's Nurses' Health Study, is the latest piece of the increasingly complicated estrogen puzzle. The study looked at estrogen use among 28,835 nurses and whether long-term use affected risk for breast cancer.

The study showed there was no statistically significant increase in breast cancer risk with up to 20 years of estrogen use. But after 20 years of use, the risk of breast cancer jumped by 42%, according to the report published today in the Archives of Internal Medicine. The data also suggested that the breast cancer risk may be slightly lower during the first 10 years, but there weren't enough cancer cases among the women studied to make the number statistically reliable.

The data, which paint the clearest picture to date about how long a woman can use estrogen without increasing her risk for breast cancer, should be reassuring to the majority of women using hormones to relieve hot flashes and other symptoms of menopause. Of the 4.4 million U.S. women who use menopause hormones today, about 3.5 million take only estrogen. An additional 900,000 women take a combination of estrogen and progestin. (Progestin is added to blunt the effects of estrogen on the uterus and prevent endometrial cancer. Women take estrogen by itself if they've had a hysterectomy.)

Twenty years is far longer than most women today are advised to take hormones. Although duration of use varies, most doctors suggest women limit hormone use to less than five years.

But as many as 10% of menopausal women may still suffer debilitating symptoms for several years after menopause, requiring them to stay on the drugs longer. Other women who might require long-term use are those in their 30s and 40s who experience surgically induced menopause, caused by removal of their ovaries. To prevent a debilitating drop in estrogen, these women may need to stay on the drugs for 15 to 20 years until the time of natural menopause.

"This is reassuring to women who are contemplating taking estrogen alone for 10 to 15 years," says study author Wendy Chen, researcher at Brigham and Women's Hospital in Boston. "There are also a lot of women who went through menopause in the '70s and '80s who have been on estrogen for a long period of time. The question is should they still remain on estrogen?"

While the latest research is good news for most women using menopause hormones, it continues to raise questions about progestin and whether it's the real culprit in many of the health risks recently associated with hormone use. Studies have shown that using estrogen and progestin in combination is linked with a slightly higher risk of breast cancer after about five years of use.

The new data from the nurses study are also consistent with a controversial finding of the government-funded Women's Health Initiative. The WHI reported in April that using estrogen for an average of seven years didn't increase the risk of breast cancer and may even have lowered it. The study shocked the medical community because it contradicted decades of earlier research that suggested estrogen was linked with a higher risk for breast cancer.

But one big problem with the WHI is that it was stopped a year early, because government health officials cited a slight increase in stroke risk among older women in the study. The WHI investigators lamented that year of lost data because it would have added credibility to the surprising finding.

Now the Nurses' Health Study has looked at the estrogen-breast cancer link for far longer than a clinical trial could ever do. The nurses study is an observational study that tracks the health habits of women over time without dictating any particular treatment. A clinical trial, like the WHI that compares a treatment to a placebo, is far more expensive to conduct for long stretches of time.

"There isn't ever going to be a clinical trial in which women will take estrogen for 15 or 20 years," says Dr. Chen. "It's a relevant question to women who are currently on estrogen, and they're deciding `How long should I remain on it?'"

Most of the nurses' data before the 20-year mark didn't reach the point of statistical significance, meaning the findings could just be due to chance. The data showed that breast cancer risk was about 10% lower in the first 10 years of estrogen use, but the risk increased slightly over the next 10 years, but none of those findings were statistically meaningful because there were so few cancer cases among the women studied.

The 20-year mark was the first point in time when the data showed a statistically significant link with breast cancer. The investigators noted that among cancers that have hormone receptors for both estrogen and progesterone, which account for 44% of the cases studied, the risk for breast cancer increased sooner, at the 15-year mark.

Another important finding of the study showed that estrogen use for 20 years or more poses a higher risk to thin women than overweight women. The theory is that overweight women have more natural circulating estrogen from body fat, so hormones in a pill are less of a shock to the system than in a thin woman. The nurses' data showed that after 20 years of use, thin women had a 77% higher risk for breast cancer compared with thin women who didn't use hormones. Overweight women had a 25% higher risk after 20 years compared with overweight women who didn't use hormones.

The Wall Street Journal, April 12, 2006

Benign Finding: Study Challenges Tie of Estrogen Use To Breast Cancer --- Data Defy Longtime Beliefs, Hint at Risk for Progestin; Some Remain Skeptical --- A Hormone's Many Effects

By TARA PARKER-POPE

For years doctors have warned that using the hormone estrogen during menopause puts a woman at higher risk for breast cancer. Now data on thousands of women suggest that the warning may have been unnecessary.

Investigators in the federally funded Women's Health Initiative found that using estrogen doesn't increase the risk of breast cancer and may even lower it. Estrogen users were 20% less likely to develop breast cancer after an average of seven years taking the drug than women taking a placebo, according to results being reported today in the Journal of the American Medical Association.

The 20% figure isn't statistically significant and by itself doesn't support the use of estrogen to prevent breast cancer. But the study's data do give much-needed reassurance to millions of women who take estrogen to treat menopause symptoms or cope with the effects of a hysterectomy.

The results also raise questions about the safety of another hormone, progestin, which many women take with estrogen. Doctors started adding progestin to the hormone mix in the 1980s to help avert a form of uterine cancer. But the new data, combined with earlier Women's Health Initiative results, suggest that progestin may be the culprit in raising breast-cancer risk.

"The breast-cancer story seems to be different from what we thought," says Marcia Stefanick, the Stanford University professor who has led much of the WHI research.

Like many results from the $750 million Women's Health Initiative, the new estrogen data won't escape controversy. The WHI studies have been plagued by design challenges and differing interpretations of the data. In the latest study, more than half of the 10,739 postmenopausal women in the study stopped taking their pills. Most of the women were also overweight, a factor known to influence breast-cancer risk.

The National Institutes of Health stopped the estrogen study earlier than planned, leaving the researchers tantalizingly short of firmer answers about estrogen and breast cancer. As a result, some researchers say it's a mistake to exonerate estrogen just yet.

"This is just one of these flukes because every other bit of information we have tells you that estrogen increases risk of breast cancer in postmenopausal women," says Malcolm Pike, a professor of preventive medicine and a longtime hormone researcher at the University of Southern California's Keck School of Medicine. "The notion that says this one study can turn over every other piece of scientific evidence we possess is nonsense."

The WHI, begun in 1991, is the largest randomized clinical trial of women's health and has studied everything from low-fat diets to vitamin D. Unlike earlier large-scale studies, it randomly assigned women to take hormones or a placebo, providing a scientific way to measure the effects of hormones-taking.

Since the 1960s, women have increasingly used hormones to cope with menopause symptoms such as hot flashes, which are triggered by fluctuating levels of a woman's natural estrogen due to aging. The hormones undoubtedly relieve symptoms for many. The question has always been how the drugs influence the risk of health problems -- particularly the two biggest killers, cancer and heart disease.

The first part of the WHI raised alarms on both counts. In that part, researchers studied 16,608 older women, half taking estrogen plus progestin and the other half taking a placebo. The study was stopped early in July 2002 when safety monitoring showed that the hormone users had more heart attacks and breast cancer. Some researchers challenged the data, citing design questions including the predominance of older women in the study. Still, the breast-cancer finding seemed solid because it was in tune with earlier studies.

After the first part of the WHI was stopped, researchers continued a parallel WHI trial, which compared women who took estrogen alone against those taking a placebo. These women all had undergone a hysterectomy, or removal of the uterus. That meant they weren't at risk for cancer of the endometrium, the lining of the uterus. Since the only reason for taking progestin was to prevent endometrial cancer, these women didn't need it.

Many scientists expected that the breast-cancer risk from estrogen alone would resemble the risk from estrogen plus progestin. That view was based on several important studies in the mid- to late 1990s in which researchers tracked the health habits of women over time without dictating any particular treatment. These observational studies linked estrogen use by itself to a higher risk of breast cancer.

Thus the surprise at the new results: Far from raising breast-cancer risk, estrogen seems to offer a slight protective effect. When an initial version of the findings was published in April 2004 in JAMA, many researchers dismissed the data as a statistical anomaly that was likely due to chance.

After WHI investigators subsequently submitted a more-detailed analysis of the breast-cancer data to JAMA, reviewers for the medical journal continued to raise questions. Hormone use changes the way the breast looks in a mammogram and could make it harder to spot tumors. The reviewers wanted to be sure they were really seeing fewer cases of cancer in the estrogen takers and wanted more details about the mammograms and breast biopsies. All the questions delayed publication until today.

"It's a lot harder to publish something that goes contrary to what people believe," says Dr. Stefanick.

At this point, the WHI investigators don't believe women should use hormones to prevent breast cancer. Nonetheless, some additional analyses raise the possibility that estrogen may in fact offer protection. Because 54% of women had stopped taking pills by the study's end, investigators decided to also analyze data from just those women who consistently took their medications. Among these women, breast cancer risk was lowered by 33% -- a trend that is considered statistically valid. When investigators looked at specific cancers, estrogen appeared to lower risk for ductal carcinoma -- the most common type of breast cancer -- by 29%.

Why did earlier studies show opposite results? One answer may be that hormone users in earlier studies were more likely to get mammograms, says Rowan Chlebowski, a WHI investigator and breast-cancer researcher at the University of California, Los Angeles. Doctors would have found more cancer in estrogen users simply because they were looking harder.

In fact, one earlier study supports the new results. A little-noticed 2003 study in the Journal of Clinical Oncology looked at the mammograms of nearly 375,000 postmenopausal women. Women who used estrogen for five years or more were 8% less likely to be diagnosed with breast cancer compared with nonusers.

Still, several quirks in the WHI study population are likely to raise debate. Nearly half the women in the estrogen-only study were obese, so it's possible that the results are less applicable to thin women. The reason: Fat is a source of estrogen, and it may be that overweight women have so much natural estrogen from fat that adding more from pills doesn't make much difference.

Also, 41% of the women in the study had both their ovaries removed, a practice that can lower breast-cancer risk. Women in the WHI studies used Premarin, a complex mixture of estrogens derived from horse urine that may work differently than other forms of estrogen on the market.

The WHI study of estrogen-only users was supposed to continue through 2005 but officials at the National Institutes of Health stopped it a year early in February 2004. Although an independent safety monitoring board had narrowly decided that the study could continue, the NIH overruled it, citing a slight increase in stroke risk among the estrogen users.

In hindsight, the early end to the study made it harder to reach conclusions about estrogen and breast-cancer risk. Dr. Chlebowski says it would be "nicer" to have the data from the extra year. "The investigators wanted to keep the study open," he says, but the decision was the NIH's to make.

NIH director Elias Zerhouni says the agency consulted outside experts as well as the safety board and investigators. He says the data about stroke and blood-clot risks had to take precedence over the still-unclear breast-cancer data, which "was really counter to what we know about estrogens."

"We weighed the risk-benefit and decided it was time to protect the patients rather than look at potential positive data on the breast cancer side," says Dr. Zerhouni. "A trial when you're dealing with healthy people has to have a much lower tolerance for complications."

The WHI estrogen results could fuel new avenues of research into the role estrogen plays in breast cancer. Scientists already know that certain breast cancers thrive in the presence of endogenous estrogen -- the kind made by a woman's body. Medications such as tamoxifen or new aromatase inhibitors help stave off breast cancer either by blocking natural estrogen's effects or interfering with production of it. Yet doctors also sometimes use high doses of estrogen to treat breast cancer in certain patients.

How could adding estrogen to a woman's body possibly reduce her risk for breast cancer? Scientists think a woman's natural estrogen may affect breast-cancer risk differently than estrogen taken in the form of pills, patches and creams. However, researchers say the issue needs much more investigation.

The new results are also likely to make doctors take a harder look at progestin. Its use took off in the 1980s, after women were frightened away from estrogen because of reports that it dramatically raised the risk of uterine cancer. To solve the problem, doctors began prescribing progestin, which was known to blunt the effects of estrogen on the uterus, thereby preventing endometrial cancer.

But in trying to prevent one form of cancer, doctors may have inadvertently raised the risk of another. "It was an accepted dogma that estrogen was the bad guy for the breast and endometrium," says Kent Osborne, director of the breast center at the Baylor College of Medicine in Houston. "Now it's turning out that it's progestin that's bad for the breast and estrogen that's bad for the endometrium."

Recently some doctors have tried giving progestin only a few times a year rather than every month. This may be enough to protect the uterine lining from precancerous changes without exposing women's breasts to the long-term effects of progestin.

"I'd like to see a shift in this country away from using so much progestin," says Hugh S. Taylor, an associate professor at Yale University School of Medicine. "Many ob-gyns are thinking this but they are afraid to do it."

The Wall Street Journal, March 22, 2006

Test for Breast-Cancer Risk Could Miss Mark --- As Many as 12% of Women With Strong Family History Get Inaccurate Reading

By THOMAS M. BURTON

A widely used diagnostic test for genetic breast-cancer risk misses 10% to 12% of women who are at high risk, making them think their chance of getting cancer is lower when in fact it remains substantial, a new study shows.

The findings are based on a relatively small sample of patients. But they have potential implications for thousands of women with a family history of breast cancer, who rely on the test to guide them in protecting their health.

The test is designed to detect mutations in certain genes, known as BRCA1 and BRCA2. Women who have these mutations are known to have an 80% lifetime risk of breast cancer, and many women with a strong family history of breast cancer are advised to get tested. Women who get a positive result are faced with a wrenching choice: Live with the knowledge they will very likely get cancer, or take dramatic steps such as prophylactic mastectomies.

Of the 180,000 new U.S. breast-cancer cases each year, 5% to 10%, or up to 18,000, are a hereditary form linked to the BRCA genes, according to Mary-Claire King of the University of Washington, the lead author of the study, which is published in this week's Journal of the American Medical Association.

In the study, researchers examined a commercially available test that is the sole method used in the U.S. to detect the BRCA gene mutations. It is made by Myriad Genetics Inc. of Salt Lake City, and costs about $3,000 for a full spectrum of blood work. Dr. King and colleagues found that test misses some cancer-causing mutations. And they estimate that perhaps 10% to 12% of high-risk women who get a negative result from their commercial test in fact remain at very high risk because of what she calls "cryptic mutations" that went undetected by the test.

Precisely how many women this could affect is uncertain, but they could well number in the thousands, according to Dr. King, who is also the geneticist who first identified the presence of BRCA1. Of the approximately two million U.S. women currently living with breast cancer, Dr. King estimates that perhaps 20,000 cases could be women with the genetic mutations that would be undetected by commercial testing.

Myriad Genetics officials said the numbers probably are considerably smaller. Gregory C. Critchfield, president of Myriad's Myriad Genetic Laboratories unit, said the company is developing a new test that would resolve uncertainties for high-risk women who get negative results on their BRCA1 and BRCA2 test. The new test could be available this year, he said.

Dr. King's research nonetheless leaves a sizable question mark for many women with a strong family history of breast or ovarian cancer. Certain BRCA1 and BRCA2 mutations predispose women to a very high risk of ovarian, as well as breast, cancer. "Without appropriate education, people may take a negative test to mean they don't have to worry," said Mark Robson, clinic director of the clinical genetics service at New York's Memorial Sloan-Kettering Cancer Center. "We continue to recommend that women, even after a negative test, continue to do screening and follow-up."

The research, by Dr. King and colleagues from the University of Washington and from cancer institutes in the Slovak and Czech Republics, focuses on 300 women from families with four or more cases of breast or ovarian cancer, but with negative results in their BRCA tests. Using a separate diagnostic test called MLPA, the researchers found that about 12% in fact had genetic mutations in the BRCA1 and BRCA2 genes or in two other genes, CHEK2 and TP53, that also increase cancer risk but not as dramatically as the BRCA genes.

"Our results suggest that genetic testing, as currently carried out in the United States, does not provide all available information to women at risk," the authors write. Executives from Myriad Genetics said in an interview that these findings apply only to women in what they term "ultra high-risk families" suffering four or more cases of breast or ovarian cancer.

For high-risk women with negative test results, their next steps are complex. Dr. King and colleagues said a follow-up MLPA test "appears to be the most efficient and cost-effective strategy to identify genomic rearrangements in BRCA1 and BRCA2." However, Dr. King said the MLPA, while available in many European hospital labs, is generally not available in the U.S.

At leading cancer centers today, many doctors already have been telling women that negative test results don't mean they're in the clear. "Genetic counseling is a long-term relationship. You have to maintain that contact" with patients regardless of their BRCA test results, said Larry Norton, director of the breast-cancer center at Memorial Sloan-Kettering. Of Dr. King's research, he said, "This is a very important piece of work, but not the final word."

Now, said Dr. Norton, high-risk women with negative BRCA test results still are asked to consider the various choices they would face even if their tests were positive. That often means MRI tests instead of mammograms, because MRIs can be more precise. It generally means screening at young ages for breast and ovarian cancer. "We tend to want to screen a decade earlier than the earliest onset in their family," he said.

Some women also are choosing mastectomies to avoid cancer, and this even includes women who have received negative BRCA test results. Some women opt for removal of ovaries, as well. Screening tests for ovarian cancer are "not wonderful," Dr. Norton said. "That's one area where we strongly recommend removal of the ovaries when the child-bearing years are over."