Angelina Jolie's mother had breast cancer and died of ovarian cancer, and her maternal grandmother also had ovarian cancer — strong evidence of an inherited, genetic risk that led the actress to have both of her healthy breasts removed to try to avoid the same fate, her doctor says.

Jolie, 37, revealed on Tuesday that she carries a defective BRCA1 gene that puts her at high risk of developing breast and ovarian cancer. She had mastectomies in February followed by reconstruction with implants in April, Dr. Kristi Funk said in an interview with The Associated Press.

Funk treated Jolie at the Pink Lotus Breast Center in Beverly Hills and detailed her care on the center's website. She would not disclose when Jolie learned she carried the faulty gene, which gives a woman up to an 87 percent lifetime risk of developing breast cancer and up to a 54 percent chance of ovarian cancer.

"This family history would certainly meet any insurance carrier's criteria to cover genetic testing," Funk wrote.

It is unclear whether Jolie will have her ovaries removed, although she wrote in her op-ed piece in the New York Times that she "started with the breasts" because they posed the highest cancer risk.

Removing the ovaries is often advised for women with such gene mutations, said Dr. Charis Eng, a medical geneticist and cancer specialist at the Cleveland Clinic who had no role in Jolie's care.

"We usually say 'try to have your kids'" and then have your ovaries removed by age 40, Eng said. It's not possible to remove every speck of breast tissue, but removing the breasts and ovaries leaves very little behind that could develop cancer, so it dramatically lowers a woman's risks, she said.

On the surgery center's website, Funk described Jolie's three operations, which were done through the crease underneath each breast. Jolie's partner, actor Brad Pitt, "was on hand to greet her as soon as she came around from the anesthetic, as he was during each of the operations," Funk wrote.

On Feb. 2, Jolie had a procedure aimed at preserving the nipples, which usually are removed when a mastectomy is done to treat breast cancer. Half of the skin is lifted from the surface of the breast tissue and a small disc of tissue is taken to be checked for cancer.

The tissue proved healthy and on Feb. 16 she had the two mastectomies. Doctors also took an unusual step: injecting dye to determine which lymph nodes in her arms were draining fluid from the breasts. Those nodes would be most likely to contain cancer if any turned out to be lurking in the breast, Funk explained.

When a preventive mastectomy is done, "there's a 2 to 8 percent chance" of finding cancer, even though there was no indication of cancer beforehand, Funk said. Stitches or a tiny clip can be placed to show the location of these key "sentinel" lymph nodes in case Jolie ever were to develop cancer in the future and those nodes would need to be checked again.

Also during this operation, doctors placed a tissue expander, a balloon-like device that is slowly inflated with saline to stretch the skin and make room for a permanent implant. Even though the implant could have been done at the time of the mastectomy, Jolie chose the two-step procedure to optimize the final cosmetic appearance.

Four days after her mastectomies, "I was pleased to find her not only in good spirits with bountiful energy, but with two walls in her house covered with freshly assembled storyboards for the next project she is directing," Funk wrote on the website.

On April 27, doctors did her reconstruction, using a newer teardrop-shaped implant plus sheets of cadaver skin, which "creates like a sling under the implant" to give a more natural look, Funk said.

The website describes how women with gene mutations that raise their risk for cancer are monitored starting at age 18, but Funk said she could not disclose when Jolie was tested and learned she had the BRCA1 gene. About 5 percent to 10 percent of breast cancers and about 15 percent of ovarian cancers are thought to be due to BRCA gene mutations.

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More opt for preventive mastectomy

Don't judge us, mastectomy patient says

Angelina Jolie's surprising announcement that she'd had both breasts removed to reduce her risk of getting cancer has brought renewed attention to the controversial procedure.

Rates of women who are opting for preventive mastectomies have increased by an estimated 50 percent in recent years, experts say. And surveys show they are happy with the decision.

Splash News

Undated photo of Angelina Jolie, her mother, Marcheline Bertrand, and her brother, James. Bertrand died of cancer in 2007. She was 56.

But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring. Women can take tamoxifen or one of several newer drugs called aromatase inhibitors and reduce their risk by as much as 50 percent.

For Jolie, the chance to prevent cancer was worth losing her breasts, she wrote in the New York Times. 

Like many other women having the procedure, Jolie, who is 37 and a mother of six, says she did not want to live in dread of the cancer that killed her mother at age 56. “I decided to be proactive and to minimize the risk as much I could,” she wrote.

Since genetic tests for breast cancer risks have become available, the numbers of women choosing to be tested and then to have their breasts removed has shot up, says Dr. Todd Tuttle, chief of surgical oncology at the University of Minnesota.

Jolie said she had a mutation of the BRCA1 gene, which raises the risk of both breast and ovarian cancer. “My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer, although the risk is different in the case of each woman,” she wrote. She says she also plans to have her ovaries removed at some point.

In Jolie's case, her decision was "absolutely indicated," said Tuttle. At 37, Jolie is young to worry about breast cancer. But studies also show that the younger a woman is when she develops breast cancer, the more aggressive the disease is.

Other genes can raise or lower the risk that BRCA1 and BRCA2 mutations confer. And these mutations are rare. The U.S. Preventive Services Task Force recommends that only women with a strong family history even think about getting a BRCA genetic test –which is only 2 percent of U.S. women.

But why are so many women opting for surgery when survival rates for breast cancer are 93 percent if it’s caught at the earliest stages and 88 percent at stage 1?

“I have postulated that one of the downsides of breast cancer awareness is that there is a situation of hyperawareness. Women in the United States are just assuming they are going to get breast cancer,” Tuttle says. The actual rate is about 12 percent. About 1 in 8 U.S. women will develop breast cancer, and while 230,000 women were diagnosed with breast cancer last year, just under 40,000 died of it.

Dr. Sandra Swain, president of the American Society of Clinical Oncology, agrees that women shouldn't just assume they are at high risk. But she doesn't think there's any such thing as too much awareness.

"To me, you never can be too aware," says Swain, medical director of the Washington Cancer Institute at MedStar Washington Hospital Center. "I think people speaking out like Angelina Jolie are very good. She is very thoughtful about it." Jolie got genetic counseling and got an assessment of her own personal risk. "That's a good model," Swain said.

It’s hard to determine the precise number of women who are opting to have surgery for a medical condition they don't yet have. Private insurance companies have the best information, and there’s not an easy way to get it and compile a database.

Tuttle’s done a lot of research looking at how many women chose to have both breasts removed when cancer was found in one breast. Although the risk of developing cancer in the healthy breast is fairly low, many women choose to have both breasts removed when a tumor develops in one.

One study showed that women aged 55 and younger with a family history of breast cancer in both breasts – a high-risk group – had about a 16 percent risk of developing cancer in the second breast over the next 10 years. Older women would have an even lower risk. Yet the rates of prophylactic mastectomies among these women doubled between 1998 and 2005.

“It is pretty clear that the use of double mastectomy for women with cancer in one breast has exploded,” Tuttle told NBC News.

Another way to look at rates is to study women with a form of pre-cancer called lobular carcinoma in situ, or LCIS for short. LCIS does not always progress to cancer, but some women choose to have their breasts removed after a diagnosis, Tuttle says.

“Rates of prophylactic mastectomy for women with LCIS increased by 50 percent since the year 2000,” Tuttle said. He presented a study to the American Society of Breast Surgeons last week showing rates of women have preventive mastectomies after LCIS went from 12 percent in 2000 to 18 percent in 2009.

Jolie’s decision resonated with women like Lizzie Stark, 31, of Edison, N.J., who had a preventive double mastectomy two years ago after learning she had the BRCA1 gene. Her immediate response was empathy for the movie star – “This is a terrible decision to have to make” – and gratitude that Jolie chose to go public.

“I think it’ll make it easier, the more women who come out and talk about it,” said Stark.

Private insurers usually pay for both the removal and the reconstruction, including implants, if a doctor indicates the need. And the results are good if done by a good surgeon, studies show. Women usually feel good about their choice, also – surveys of women who have had double mastectomies show little regret.

But women may not realize just how serious the surgical procedure is, Tuttle says.

“I wonder if one of the reasons driving this trend is women underestimate the extent of this operation,” he said. “Prophylactic mastectomy with immediate reconstruction is a big operation. It can be five to six hours,” Tuttle says. “There can be complications and re-operations.”

And recovery can take a “good month”,  he added.  

“Prophylactic mastectomy is permanent and irreversible,” the National Cancer Institute cautions. “This surgery causes significant loss of sensation in the breast, which can have an impact on sexuality.”

Stark, who also had nipple-sparing reconstructive surgery, said she appreciated that Jolie made a point of saying that the surgery didn’t diminish her sexuality.

“I did feel like I lost my femininity,” Stark said. “Because it is a part of your body associated with femininity. I started wearing girlier clothes than I had before. I started wearing more makeup and plucking my eyebrows. But you don’t have to lose your femininity.”

Jolie explains the motivation behind her decision: control. "Life comes with many challenges. The ones that should not scare us are the ones we can take on and take control of," she writes.

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Angelina Jolie says she has undergone a preventive double mastectomy after being told that she had an 87 percent risk of breast cancer, along with a 50 percent risk of ovarian cancer.

In an article published in the opinion section of Tuesday's New York Times, Jolie said her decision was informed by her mother's long fight against cancer. Marcheline Bertrand died in 2007 at age 56.

Jolie said she hoped that other women would find encouragement from her story. 

"I choose not to keep my story private because there are many women who do not know that they might be living under the shadow of cancer," Jolie said in the Times article. "It is my hope that they, too, will be able to get gene tested, and that if they have a high risk they, too, will know that they have strong options." 

Jolie, an Oscar-winning actress and activist, said she carries a gene, BRCA1, that increases the risk of breast and ovarian cancer. According to Jolie and a fact sheet from the Cancer Institute at Stanford Medicine, women with the BRCA1 gene have an average of a 65 percent lifetime risk for breast cancer, along with heightened risk of the cancer at an early age. Jolie is 37. 

Jolie said three months of medical procedures that the mastectomies involved were completed April 27. She said the surgery included implants to reconstruct her breasts.

She said that her partner, Brad Pitt, was present for the surgeries. She said her six children, who range in age from 11 to 4, saw nothing that made them uncomfortable.

"They can see my small scars and that’s it," Jolie wrote. "Everything else is just Mommy, the same as she always was. And they know that I love them and will do anything to be with them as long as I can."

Other famous women with the BRCA1 or BRCA2 genes have undergone preventive double mastectomies, including reality star Sharon Osbourne, wife of rocker Ozzy.

"I've had cancer before and I didn't want to live under that cloud," Osborne said in an interview last fall.

In January, Miss America contestant Allyn Rose, representing the District of Columbia, announced that she carries another genetic mutation -- not BRCA1 or BRCA2 -- and plans to have a double mastectomy after her year of serving as Miss D.C.

Friends and fans were quick to support Jolie via messages on Twitter. Actress Marlee Matlin called her "brave, honest (and) strong." And "Veronica Mars" star Kristen Bell praised Jolie's article as "admirable."

Slideshow: Angelina Jolie

Toby Melville / Reuters

Highlights from her Oscar-winning acting career, family life with Brad Pitt and worldwide humanitarian efforts.

Launch slideshow

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A batch of new gene discoveries nearly doubles the number of genes known to cause three of the most common cancers – breast cancer, prostate cancer and ovarian cancer. While each gene alone affects only a small number of people, taken together they help explain one-third of cases of these cancers, researchers reported on Wednesday.

It took a giant study to find all the genes – nearly 200,000 people took part at 160 institutions. The findings can not only help doctors decide who needs more frequent screening for cancer, but may eventually help target treatments that will work better for particular patients, the researchers said.

People with several of the genetic changes linked with cancer will have a much higher-than-average risk of the cancers, the researchers said. They published their findings in a series of 13 papers in several medical journals, including Nature Genetics and Nature Communications.

“By looking for people who carry most of these variations we will be able to identify those who are at the greatest risk of getting these cancers and then targeting screening tests to these individuals,” said Douglas Easton of Britain’s University of Cambridge, who led some of the studies.

“We now have 76 common genetic variants which are associated with breast cancer risk,” Easton told a news conference. Combined with other research, including the well-known breast cancer genes BRCA1 and BRCA2, genetic susceptibility explains 40 percent of breast cancer cases, he said.

“Any one of those (variants) is so tiny they don’t affect much,” Dr. Fergus Couch of the Mayo Clinic in Rochester, Minn., who worked on the project, told NBC News. “But when we put them together into a complex model … It’s the power of everything together that can make a difference.”

The researchers found 23 new genes linked with prostate cancer and three more for ovarian cancer. Now researchers know about 78 different genes associated with higher prostate cancer risk, and 16 of them are associated with aggressive disease.

The three cancers affect 2.5 million people globally, killing about a third of them. They all are driven by hormones.

“The most immediate practical application is probably going to be for women already at high risk of (breast cancer),” Easton said. A woman with a BRCA1 or BRCA2 mutation already has a very high chance of breast cancer. If she also has one or more of these other alterations, she’s at even higher risk.

Women who have a BRCA1 mutation along with most of the other, newly discovered mutations have an 80 percent chance of developing breast cancer by age 80, the researchers found.

“The 1 percent of people who have lots of these alterations could see their risk of developing prostate cancer increase by nearly 50 percent and breast cancer by 30 percent,” Easton said.

People may soon be able to take a genetic test to see what their risk is. They could then opt for early screening to watch for the disease. “This will be ready for prime time in a little more than a year,” Couch predicted.

Right now, guidelines vary on when women should get mammograms, for instance. Some guidelines call for annual screening starting at age 50; others say women only need them every two years.

A woman with a high genetic risk might opt to start having mammograms at age 30 or younger. There’s also confusion around testing for prostate cancer. U.S. experts say men shouldn’t be routinely screened using a blood test called a PSA test, because it causes too many “false positives” – when men are initially told they may have cancer but it turns out they don’t.

But men with a high genetic risk might opt to have frequent PSA tests.

“These results are the single biggest leap forward in finding the genetic causes of prostate cancer yet made,” said Rosalind Eeles  of Britain’s Institute of Cancer Research.

“They allow us, for the first time, to identify men who have a very high risk of developing prostate cancer during their lifetime,” she added.

The genes play a variety of roles in cancer. Some are supposed to stop the out-of-control growth that marks a tumor; some help cancer cells spread.

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NBC News

The chatroom posts always start with words like "Help!” or “I’m flipping out”. And they’re all the same story -- a woman having a routine mammogram is called to come back for follow-up. She’s not told why, and the wait can be as long as six months.

A study published on Monday shows many women suffer intense stress after such a call -- and  that the stress lasts long after a follow-up mammogram, ultrasound or biopsy shows they are cancer-free.

Most women are just fine, of course. But the study, published in the Annals of Family Medicine, suggests that doctors need to address the possibility of anxiety, even extreme anxiety, over a false-positive test result.

“False-positive findings on screening mammography causes long-term psychosocial harm: Three years after a false-positive finding, women experience psycho-social consequences that range between those experienced by women with a normal mammogram and those with a diagnosis of breast cancer,” John Brodersen and Volkert Dirk Siersma of the University of Copenhagen concluded in their report.

A 42-year-old woman wrote about her experience in one women’s health chatroom. “LADIES-HELP I’m flipping out,” she writes. “I am scared out of my mind. I have dry heaves because there’s nothing to vomit.”

The woman, whose identity could not be confirmed, got a letter asking for a follow-up visit to get additional imaging after a routine mammogram. “I called to make the appt & it's going to be A WEEK before they can fit me in!” she writes. “I am waiting for a call back from my Dr. to see if I can get any more info. I am SO SCARED!!!!!!!”

Talya Salz, who’s done some research on the anxiety that follows mammograms, says it’s not hard to imagine what women are going through. “At least in the initial period, you are going through the motions of imagining what it would be to have breast cancer,” Salz,  who studies cancer survivors at Memorial Sloan-Kettering Cancer Center in New York, told NBC News.

Salz and colleagues did their own study of the psychological impact of having a false-positive mammogram in 2010. Their meta-analysis -- a study of studies -- showed that women who got a false positive were more likely to be anxious and distressed about breast cancer. Other studies have shown a similar effect. The latest study followed 454 women for three years.

“The risk of having false positives differs greatly from one country to another. The cumulative risk in Europe and the United States of false positives in 10 screening rounds ranges from 20 percent to 60 percent,” Broderson and colleagues wrote.

They compared women who had an abnormal mammogram that turned out to be nothing to women who did have breast cancer.

“Women with breast cancer experienced greater negative changes in psychosocial consequences than women with false positives, who again experienced greater negative changes than women with normal findings,” the researchers wrote. “In the two scales regarding inner calm and existential values, however, there was no statistically significant difference between women with false positives and those with breast cancer up to six months’ follow-up.”

Breast imaging specialist  Dr. Alice Rim of the Cleveland Clinic in Ohio says this means doctors need to do a better job right after women get their mammograms.

“One of the most important things that I can do as a physician in a screening program is make sure the doctors have a talk with their patients,” said Rim, who was not involved with the latest study. “What does it mean when they call you back? It could be nothing.”

What looks like a tumor on an X-ray may be a cyst, or it maybe nothing at all. Sometimes growths just disappear, for reasons doctors don't quite understand. "You have to take a 3-dimensional object -- a breast -- and smash it onto a two-dimensional view," Rim said.

Rim says her clinic is careful about sending letters to women saying they need a follow-up mammogram. “Getting the letter is very scary,” she said. “Sometimes women don’t know what to do. They are freaking out.” Rim said often her clinic will call a patient before she gets the letter to explain what it means -- and what it doesn’t mean.

”We try to hold off on sending letters on a Friday or Saturday because there is no one to call,” Rim said.

This anxiety is of one of several reasons the U.S. Preventive Services Task Force recommends that women over 50 only get a mammogram every other year, and why the group says it might not be necessary for every woman aged 40 to 50 get a mammogram.

“We don’t think about the negative results of all the testing that we do until we get a scary result,” Salz said. But Salz and Rim agree -- this doesn’t mean women should not get mammograms, which can find breast cancer before it has spread and while it is easiest to treat.

While women may be anxious, Salz says, it doesn’t usually reach the point of damaging their lives. “We are not talking about anxiety that is going to send you to get medication,” she said.

But anxiety may deter women from coming back for their next routine screening -- and that’s not good, Salz said.

Cutting back to screening every other year can cut back the anxiety, too, a study funded by the National Cancer Institute earlier this year found. It found that over 10 years, 61 percent of women who have annual mammograms will get called back for what turns out to be a false positive, compared to 42 percent of women getting the screening tests every other year.

And another study published Monday confirms that women can safely skip every other year.

The team from the University of California San Francisco and Seattle’s Group Health Research Institute looked at data from more than 900,000 women. They found that women aged 50 to 74 who got screened every other year were no more likely to have advanced stage cancer or big tumors than women screened more frequently -- even if they had so-called dense breasts, which are harder to read on an X-ray.

“For women 50 to 74 years old with dense breasts who are cancer-free, we estimated that more than half will be recalled for additional mammography at least once over the course of 10 years of annual screening,” said Rebecca Hubbard of Group Health Research Institute, who worked on the study.

“Screening every other year decreases this risk by about a third. The risk of false-positive results is even higher for women who begin annual screening at age 40.”

But the study also found that for women 40 to 49 who had extremely dense breasts, if they only got screened every other year they were almost twice as likely to have advanced stage cancer if a tumor was later found, and more than twice as likely to have a large tumor.

Women under 50 with dense breasts need to decide with their doctors whether to have annual mammograms, they wrote in the Journal of the American Medical Association’s JAMA Internal Medicine. But they should also “be informed that annual screening leads to a high cumulative probability of a false-positive mammography result because of the additional screening examinations.”

As for the 42-year-old woman who was so anxious she vomited?

"I had a biopsy done last week. The nurse called me with my results this morning...& they were benign!" she wrote. "I am very relieved! This has been the longest week of my life."

By Sharon Begley
Reuters
Women who have ever had breast cancer might want to walk away from the brie, the butter and the black cherry (and every other flavor) ice cream. 

According to a study of 1,893 women, breast cancer survivors who average as little as one serving per day of high-fat dairy foods have a 49 percent higher risk of dying from breast cancer than those who eat little or no high-fat dairy.

In absolute terms, breast cancer survivors who consumed the most high-fat dairy had about a 12 percent risk of dying of the disease.

The elevated mortality risk is therefore "modest," said lead author Candyce Kroenke, a staff scientist at Kaiser Permanente, the nonprofit healthcare provider. "But since it may not be so difficult to lower your consumption of high-fat dairy, I think if you have breast cancer it's worthwhile."

The research, published on Thursday in the Journal of the National Cancer Institute, is notable because more than a dozen studies since the late 1980s have examined whether consuming milk, cheese, ice cream and other dairy products is related to breast cancer. The results have been a confusing muddle: Some studies found that women who eat a lot of dairy have a higher risk of breast cancer, others found they have a lower risk and still others found no effect either way.

The Kaiser study is the first to separate out the effects of high- and low-fat dairy on women diagnosed with breast cancer.

The hormone connection might apply beyond breast cancer. A 2012 study found that drinking more whole milk was associated with worse survival among men with prostate cancer, while skim milk was associated with higher survival.

"This is a very well-done study by highly regarded researchers," said Dr. Michelle Holmes, associate professor of medicine and epidemiology at Harvard Medical School and Harvard School of Public Health, who was not involved in the research. It advances scientists' understanding of how diet affects breast cancer, she said, and presents women with a simple dietary choice: "It's for each woman to decide, but if you don't eat high-fat dairy you can get the same nutrients from other sources," including low-fat versions.

Total dairy intake had no effect on how the women - who had been diagnosed with stage 1, 2 or 3A invasive breast cancer and most of whom were post-menopausal - fared over the 11.8 years, on average, that the researchers tracked them.

But high-fat dairy, which means whole milk or cream and anything made with them such as cheese and ice cream, did make a difference.

Breast cancer survivors who ate one or more servings per day (according to a 120-item questionnaire they answered) also had a 64 percent greater risk of dying from all causes, but that was expected: A high-fat diet has long been associated with cardiovascular disease, among other illnesses.

The cancer risk was more surprising, if only because scientists have speculated that the vitamin D and calcium in milk might protect against cancer.

Instead, the estrogens in milk might be the problem, researchers say. These hormones, which promote some breast cancers, reside in milk fat. Less milk fat means less estrogens, so the estrogen content of skim, 1 percent and 2 percent milk and products made from them is relatively low.

Another reason to suspect estrogens rather than fat itself was that eating more saturated fat of all kinds did not raise the women's chances of dying of breast cancer as strongly as high-fat dairy did. That suggests that fat consumption per se is unrelated to breast-cancer mortality: nuts, chocolate, coconut and vegetable fats such as those in avocados did not increase the risk. 

Courtesy of Stephanie Carson

Stephanie Carson, 38, was diagnosed with breast cancer at 29. She's part of a growing trend of very young women who are diagnosed with breast cancer that has spread.

More young women are being diagnosed with advanced breast cancer, doctors reported on Tuesday. It is a very small increase in a group of people who only rarely develop cancer, but it’s significant enough to have experts asking why.

The biggest increase was seen in women aged 25 to 34. It’s bad news because when women are diagnosed this young, usually the cancer is more aggressive, there’s no good way to screen for it and because there is no cure, even if the women can control it they face decades of life as breast cancer patients.

Stephanie Carson is one of them. Diagnosed at age 29, she’s now 38 and on disability from her job as a software engineer. Breast cancer robbed her and her husband of all hope of having a family.

“At the time it was definitely a shock. The cancer tumor was literally growing before my eyes,” Carson told NBC News. “Every day it was getting bigger, so it was very aggressive.” She had a double mastectomy, but the cancer had already spread to both her lungs.

This is what doctors believe is typical of breast cancer in younger women: It grows faster, spreads more quickly, and is harder to treat. While the five-year survival rate for breast cancer that has not spread is 93 percent, for women 39 and under whose cancer has spread, it’s only 31 percent.

Dr. Rebecca Johnson of Seattle Children's Hospital and University of Washington in Seattle was working with a cancer nonprofit, Critical Mass: The Young Adult Cancer Alliance and wanted to see if there were any differences in rates of cancer for young adults.

Johnson, a pediatric oncologist and breast cancer survivor herself, looked at National Cancer Institute data from 1973 to 2009. She and colleagues broke it down by age, ethinic group, diagnosis and other factors.

They found a steady increase starting in 1976 of breast cancer that had spread out of the breast among 25- to 39-year-old women. The rate went from 1.53 per 100,000 women in 1976 to 2.9 per 100,000 women in 2009, Johnson and colleagues wrote in their report in the Journal of the American Medical Association. That represents an average increase of just 2.07 percent per year, a relatively small rise, but it shows no signs of abating, the authors noted.

“This change translates into a tripling of the incidence of metastatic breast cancer over the 34-year period,” Johnson told NBC News. “In 1975, our projections show there were about 250 cases per year of metastatic breast cancer in young adult women. In 2009, it was about 800.”

The study looks only at data, and Johnson isn’t sure of why the cases might be increasing. It’s not more or better screening --women this young are not routinely screened for breast cancer. She also doesn’t believe doctors are finding more cases because they are trying harder to see if the cancer has spread in these young women.

“If that was the case, then it would be like a pie, with a larger piece of the pie being distal disease,” Johnson said. “But there’s been no decrease in any other stage of breast cancer.’

Obesity is a risk factor for breast cancer in middle-aged women and that’s worth more study, Johnson says. But she notes that obesity actually lowers the risk of breast cancer among the youngest women. Some studies have suggested a combination of obesity, a lack of exercise and overeating may raise the risk and that’s worth looking at, she says.

It is possible chemicals could somehow be a cause. There are also theories that viruses may be involved -- a virus causes cervical cancer and head and neck cancer, for instance.

Dr. Sandra Swain, a breast cancer specialist at Washington Hospital Center in Washington D.C. and president of the American Society of Clinical Oncology, says women are putting off pregnancy longer and that could have an effect.  “Having kids younger decreases the risk of breast cancer by half,” she says.

Swain also believes higher rates of obesity may be a factor. She stresses that the results should be confirmed in larger studies, and says even if they are confirmed, the findings are not a cause for panic.

“There’s actually a decrease in mortality, especially in younger women, probably because our treatments are better,” Swain says.

Carson’s a living example of this. She’s had surgery, radiotherapy, several types of chemotherapy and treatment with new “smart bomb” drugs. She’s about to start a new round of treatment with a drug the Food and Drug Administration approved just last week – Kadcyla -- which combines a strong chemotherapy drug with Herceptin, a genetically engineered immune system protein that homes in on tumor cells.

“Hopefully it will knock things out again,” Carson says cheerfully. She’s covered by her husband’s health insurance -- he’s a software engineer, too.

All the therapy has taken a toll.

“The side-effect that hurt me the most recently -- I was in a clinical trial in Seattle three years ago, an immune therapy trial, and it gave me headaches,” Carson says. “I have had a headache every day since since then. I have had a headache for three years. That is one reason I had to stop working.”

Carson uses some alternative approaches to cope, like qigong, a meditative version of a Chinese martial art. And she works with other young women with breast cancer through the Young Survival Coalition.

“I can help them deal with some of the feelings of isolation,” Carson says. “It is strange to be this age and on disability. You feel kind of retired, but your peers are all raising families and working full time,” she adds. “I can relate to the feeling of not being able to have children.”

Young cancer patients also have higher rates of other cancers, such as leukemia, that are caused by the chemotherapy and radiation. They also risk heart disease, for the same reasons.

Breast cancer is the biggest cancer killer of U.S. women, after lung cancer. It will be diagnosed in about 235,000 U.S. men and women this year and will kill 40,000, according to the American Cancer Society.

The risk goes up with age. About one in eight cases of invasive breast cancer are found in women under 45. Less than 1 percent -- 0.43 percent -- of women aged 30 will develop breast cancer within the next 10 years, and only 4 percent will get it by age 70. About 35 out of every 1,000 women now aged 60 will develop breast cancer over the next 10 years, according to the Centers for Disease Control and Prevention.

Johnson, the researcher, is now 44. She was one of the luckier young survivors of breast cancer. She was diagnosed at 27 and her tumor had not spread beyond the breast. She found a lump by chance and waited several months before she had it checked. “I was super-busy,” she said. So her advice to young women? "If there’s a general take-home message it would just be for awareness. If you find a breast lump, you need to know that breast cancer can happen,” she said.

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• Breast-saving therapy may save lives, too

The Food and Drug Administration approved a new "smart bomb" drug on Friday that can help women with one of the most hard-to-cure types of breast cancer.

The new drug added several months of life to women with a type of breast cancer called HER2-positive breast cancer, whose tumors had spread despite treatment. While it wasn’t a cure, it did add some healthy months of life to patients whose outlook was otherwise hopeless.

The drug is called Kadcyla, and it works in an unusual way. It combines an older drug, Herceptin, with a highly toxic type of chemotherapy called DM1. The Herceptin hones in on the tumor cells, which absorb the package and are then destroyed by the DM1, which is too strong to deliver like standard chemotherapy. It’s a member of a new class of drugs called antibody-drug conjugates or ADCs.

“Kadcyla delivers the drug to the cancer site to shrink the tumor, slow disease progression and prolong survival," Dr. Richard Pazdur, director of the FDA's office of hematology and oncology products, said in a statement.

In a trial of 991 women with advanced HER2 breast cancer, those who got Kadcyla lived on average 5.8 months longer than those getting more standard chemotherapy, researchers reported last year in the New England Journal of Medicine. It meant about 2 ½ years of life after diagnosis, compared to two years for those on standard therapy.

“Only a few studies in metastatic breast cancer have shown an improvement in overall survival. It’s tough to do,” Dr. Sunil Verma of the Sunnybrook Odette Cancer Centre in Toronto, who led the study, said in a statement on the National Cancer Institute’s website.

Genentech, which makes the drug, is now focusing on the ADC formula. The hope is it can cause fewer side-effects than ordinary chemo, which can affect healthy tissue. Herceptin is a synthetic immune system protein or monoclonal antibody called trastuzumab.

“We currently have more than 25 antibody-drug conjugates in our pipeline and hope this promising approach will help us deliver more medicines to fight other cancers in the future,” Dr. Hal Barron, the company’s chief medical officer, said in a statement.

It's not cheap. A nearly 10-month course of therapy costs $94,000, Genentech says.

Genentech promised the FDA it would help patients pay for it. “People who do not have health insurance, or who have reached the lifetime limit set by their insurance company, might qualify to receive Kadcyla free of charge,” the company said in a statement. Herceptin alone costs more than $4,000 a month.

The drug is not without side-effects. It can damage the heart, liver and lungs and pregnant women can’t take it.

Breast cancer is the biggest cancer killer of women, after lung cancer. It’s diagnosed in about 235,000 U.S. men and women every year and kills 40,000, according to the American Cancer Society.

About 20 percent of cases are known as HER2-positive breast cancer. That means the tumor cells make extra amounts of a protein called human epidermal growth factor receptor 2. It makes for a very aggressive type of cancer and it’s more likely to come back after treatment than other breast cancers.

Women newly diagnosed with HER2 breast cancer should still be treated first with Herceptin alone for a year, the National Cancer Institute says. But doctors may test the new drug in some volunteers to see if it works better.

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By Denise Lavoie 
Associated Press

Four sisters who claimed their breast cancer was caused by a drug their mother took during pregnancy in the 1950s reached a settlement Wednesday with Eli Lilly and Co. in the first of scores of similar claims around the country to go to trial. 

Neither Eli Lilly nor lawyers for the women would disclose the financial terms of the settlement, which was announced on the second day of testimony during a federal trial in Boston.

Eli Lilly said it continues to believe its medication "did not cause the conditions alleged in this lawsuit" but the settlement was in its "best interest."

"Settling this trial helps us get back to what we want to focus on as a company; developing important new medications through research and partnerships with doctors and patients," it said in a statement.

A total of 51 women, including the Melnick sisters, filed lawsuits in Boston against more than a dozen companies that made or marketed a synthetic estrogen known as DES.

DES, or diethylstilbestrol, was prescribed to millions of pregnant women over three decades to prevent miscarriages, premature births and other problems. It was taken off the market in the early 1970s after it was linked to a rare vaginal cancer in women whose mothers used it.

Studies later showed the drug did not prevent miscarriages.

Attorney Aaron Levine, representing the Melnick sisters, told the jury during opening statements that Eli Lilly failed to test the drug's effect on fetuses before promoting it as a way to prevent miscarriages.

Lawyer James Dillon, for Eli Lilly, told the jury that there was no evidence the drug causes breast cancer in the daughters of women who took it.

Dillon also said that no medical records show the mother of the four Melnick sisters took DES or that, if she did take it, it was made by Eli Lilly. Leading researchers at the time recommended that DES be used for pregnant women who had consecutive miscarriages, he said.

DES was not patented and was made by many companies.

The Melnick sisters, who grew up in Tresckow, Pa., said they all developed breast cancer in their 40s.

Levine told the jury their mother did not take DES while pregnant with a fifth sister and that sister has not developed breast cancer.

The four Melnick sisters also had miscarriages, fertility problems or other reproductive tract problems long suspected of being caused by prenatal exposure to DES. They were diagnosed with breast cancer between 1997 and 2003 and had treatments ranging from lump-removal surgery to a full mastectomy, radiation and chemotherapy.

Thousands of lawsuits have been filed alleging links between DES and vaginal cancer, cervical cancer and fertility problems. Many of those cases were settled.

Attorney Andrew Meyer, who's handled numerous medical malpractice cases, said the settlement in this case could signal settlements in other cases.

"When one settles a case, they recognize they can lose it," he said. "The reason they can lose it is because there's enough evidence for the plaintiffs to be able to win it. So it's not just optics, it isn't."

Columbus, Ohio, resident Irene Sawyer also is suing Eli Lilly, alleging that her prenatal exposure to DES caused her breast cancer. She called the settlement "a huge victory" for DES daughters.

"The bottom line is that this company put out a drug without testing, without knowing the consequences of this drug," she said. 

It's wonderful, she said, that drug companies "are starting to realize this is not right, that there are consequences."

The discovery that a protein which triggers milk production in women may also be responsible for making breast cancers aggressive could open up new opportunities for treatment of the most common and deadliest form of cancer among women.

Found in all breast cells, the protein ELF5 tries to activate milk production even in breast cancer cells, which does not work and then makes the cancer more aggressive, according to scientists in Australia and Britain.

"The discovery opens up new avenues for therapy and for designing new markers that can predict response to therapy," said lead author Professor Chris Ormandy from the Garvan Institute of Medical Research in Sydney.

In 2008, Ormandy's work linked ELF5 to milk production.

The latest research by Ormandy and his team, published in the journal PLOS Biology on Friday, went a step further to find the link between ELF5 and breast cancer.

"Cancer cells can't respond properly (to ELF5), so they ... acquire some characteristics ... that make the disease more aggressive and more refractory (resistant) to treatment with existing therapies," Ormandy said by telephone.

Ormandy and his team grew human breast cancer tissues, genetically manipulated to contain high amounts of ELF5, in petri dishes and saw how the protein proliferated aggressively.

Findings may help targeted therapy

Breast cancer is the most commonly diagnosed cancer and the top cause of cancer death among women, accounting for 23 percent of total cancer cases and 14 percent of cancer deaths in women.

To decide on treatment, doctors normally need to find out if the cancer has receptors for the hormones estrogen and progesterone, which, in the case of breast cancer patients, promote growth in their tumors.

Two-thirds of breast cancers are usually positive for estrogen receptors, which then require anti-hormonal therapies that lower estrogen levels in the patient or block estrogen from supporting the growth of the cancer.

For the remaining one-third of patients, their cancers do not have receptors, which means they won't benefit from hormonal therapies. Such patients are usually given other treatments, such as chemotherapy.

Ormandy's team found that cancers with these receptors had low levels of ELF5, while those without receptors had significantly higher levels of the protein.

"What we have shown in this paper is high ELF5 tumors are dependent on ELF5 for their proliferation and if we block ELF5 in high ELF5 tumors, we will block proliferation and that will treat the tumor," Ormandy said.

"If we can develop a drug that targets ELF5, it will be very useful for that group of women," he said.

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Breast cancer patients who take the drug tamoxifen for 10 years instead of just the recommended five can further cut their chances of having the disease come back or kill them, researchers reported on Wednesday.

The surprise findings could change treatment, especially for younger women. Earlier research suggested that taking the hormone-blocking drug for longer than five years didn't help and might even be harmful.

In the new study, researchers found that women who took tamoxifen for 10 years lowered their risk it would come back by 25 percent. They were 29 percent less likely to eventually die of breast cancer compared to those who took the pills for just five years.

In absolute terms, continuing on tamoxifen kept three additional women out of every 100 from dying of breast cancer within five to 14 years from when their disease was diagnosed. When added to the benefit from the first five years of use, a decade of tamoxifen can cut breast cancer mortality in half during the second decade after diagnosis, researchers estimate.

Some women balk at taking a preventive drug for so long, but for those at high risk of a recurrence, "this will be a convincer that they should continue," said Dr. Peter Ravdin, director of the breast cancer program at the University of Texas Health Science Center in San Antonio.

He reviewed results of the study, which was being presented Wednesday at a breast cancer conference in San Antonio and published by the Lancet medical journal.

About 50,000 of the roughly 230,000 new cases of breast cancer in the United States each year occur in women before menopause. Most breast cancers are fueled by estrogen, and hormone blockers are known to cut the risk of recurrence in such cases.

Tamoxifen long was the top choice, but newer drugs called aromatase inhibitors — sold as Arimidex, Femara, Aromasin and in generic form — do the job with less risk of causing uterine cancer and other problems.

But the newer drugs don't work well before menopause. Even some women past menopause choose tamoxifen over the newer drugs, which cost more and have different side effects such as joint pain, bone loss and sexual problems.

The new study aimed to see whether longer treatment with tamoxifen could help.

Dr. Christina Davies of Britain’s University of Oxford and other researchers assigned 6,846 women who already had taken tamoxifen for five years to either stay on it or take dummy pills for another five years.

They saw little difference in the groups five to nine years after diagnosis. But beyond that time, 15 percent of women who had stopped taking tamoxifen after five years had died of breast cancer versus 12 percent of those who took it for 10 years. Cancer had returned in 25 percent of women on the shorter treatment versus 21 percent of those treated longer.

Tamoxifen had some troubling side-effects: Longer use nearly doubled the risk of endometrial cancer. But it rarely proved fatal, and there was no increased risk among premenopausal women in the study — the very group tamoxifen helps most.

"Overall the benefits of extended tamoxifen seemed to outweigh the risks substantially," Dr. Trevor Powles of the Cancer Centre London wrote in an editorial published with the study.

The study was sponsored by cancer research organizations in Britain and Europe, the United States Army, and AstraZeneca PLC, which makes Nolvadex, a brand of tamoxifen, which also is sold as a generic for 10 to 50 cents a day. Brand-name versions of the newer hormone blockers, aromatase inhibitors, are $300 or more per month, but generics are available for much less.

The results pose a quandary for breast cancer patients past menopause and those who become menopausal because of their treatment — the vast majority of cases. Previous studies found that starting on one of the newer hormone blockers led to fewer relapses than initial treatment with tamoxifen did.

Another study found that switching to one of the new drugs after five years of tamoxifen cut the risk of breast cancer recurrence nearly in half — more than what was seen in the new study of 10 years of tamoxifen.

"For postmenopausal women, the data still remain much stronger at this point for a switch to an aromatase inhibitor," said that study's leader, Dr. Paul Goss of Massachusetts General Hospital. He has been a paid speaker for a company that makes one of those drugs.

Women in his study have not been followed long enough to see whether switching cuts deaths from breast cancer, as 10 years of tamoxifen did. Results are expected in about a year.

The cancer conference is sponsored by the American Association for Cancer Research, Baylor College of Medicine and the UT Health Science Center.

By Julie Steenhuysen and Steve Orlofsky
Reuters

As many as a third of cancers detected through routine mammograms may not be life threatening, according to a study published on Wednesday that raises fresh questions about the benefits of breast cancer screening.

The study, which looked at three decades of U.S. government data, found more than 1 million women may have been over diagnosed for breast cancer, needlessly exposing them to the anguish of a breast cancer diagnosis and the ordeal of treatment.

"It's a lot of women. It's a very substantial harm," said Dr. Gilbert Welch of The Dartmouth Institute for Health Policy & Clinical Practice in New Hampshire.

But proponents of mammograms have already begun poking holes in the study, by Welch and Dr. Archie Bleyer of St. Charles Health System in Oregon and published in the New England Journal of Medicine. While mammograms are not perfect, the proponents say, their benefits still outweigh the risks.

Welch has made overdiagnosis a major focus of his research. In an earlier study, he concluded that as many as 1 million U.S. men had been over diagnosed with prostate cancer since the introduction in 1986 of the widely used PSA test.

Such studies contradict the deeply ingrained belief that cancer screening is always good because it saves lives, an idea that is being steadily challenged by studies examining the harms of screening.

"We're not the first to suggest this, and it has come at a very huge human cost - the cost of telling a large number of women they have cancer and treating women for cancer with chemotherapy and radiation and surgery," Welch said in a telephone interview.

In 2009, the U.S. Preventive Services Task Force, a government-backed advisory panel, issued new guidelines that suggested women should start routine mammograms at age 50 rather than 40, in part because the tests have such high false positive rates and the benefits in lives saved did not outweigh the worry and anguish caused by the false positive results.

That conclusion, which was based on a review of published studies, contradicted years of messages about the need for routine breast cancer screening starting at age 40 and triggered a backlash from cancer doctors, advocacy groups and lawmakers who said the tests save lives and are worth the risk of a false positive test result every now and then.

An independent panel of advisers in Britain that reviewed data from 11 studies backed up critics of the task force, saying that for every 10,000 50-year-old women invited to have a mammogram over the next 20 years, screening would prevent 43 deaths and result in 129 cases of over diagnosed breast cancers, preventing one breast cancer death for every three over diagnosed cases.

The matter, however, is still far from settled.

Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, said the new study was an "interesting conversation starter" but not the final say about the value of mammography in the early detection of breast cancer.

"It points out issues that many if not all experts agree on, but the degree of the number of women have been impacted and the true impact of the negative side of mammography is something that other researchers would disagree with," he said.

In the latest study, Welch and Bleyer looked to see how well mammography was working as a screening tool.

They figured that to reduce the rate of death from cancer, screening needs to not only find more early-stage cancers; it must also reduce the number of cancers that are discovered at a late stage, when treatments are less likely to work.

Using government health and census data, the team compared breast cancer diagnosis between 1976-1978, before mammogram screening was widely used, with data in 2006-2008, when routine mammograms had become well established.

They found that the introduction of screening mammography in the United States has doubled the number of cases of early-stage breast cancer detected each year, but the rate at which women are diagnosed with late-stage cancer has only fallen by 8 percent.

"You see with mammography a dramatic increase in early-stage disease, but you don't see much compensatory decrease in late-stage disease. That means you are finding a whole lot of early cancers that were never destined to become late-stage," Welch said.

Welch said that mammogram screening is likely not doing much to catch cancers at an even earlier stage of the disease, when they are more treatable.

The researchers estimated that breast cancer was over diagnosed in 1.3 million U.S. women in the past 30 years. In 2008 alone, they estimated that breast cancer was over diagnosed in more than 70,000 women, accounting for 31 percent of all breast cancers diagnosed.

Welch said the findings cannot answer the question of whether women should get screened for breast cancer, nor does it suggest that there are no benefits, but the findings do challenge the assumption that mammograms are always a good idea.

"I can't discount that there may be a tiny fraction of women who are helped by screening, but we can say it is very small - much smaller than conventional wisdom," he said.

Others were quick to dismiss the findings, saying the study by Welch and Bleyer was fundamentally flawed because it underestimates the annual rate of breast cancer growth.

Dr. Debra Monticciolo, a spokeswoman for the American College of Radiology and president of Society of Breast Imaging, said the paper was an "extensive analysis based on false assumptions."

For their analysis, the researchers assumed in their "best guess" estimate that breast cancer rates would remain fairly stable over the study period, increasing at a rate of about a quarter of a percent a year.

"They are off by a factor of 4," said Monticciolo, who said the real figure is closer to 1 percent increase per year.

"If you recognize breast cancer had been increasing for 1 percent per year, there is no overdiagnosis."

Welch dismissed the criticism as a "circling of the wagons" by a specialty group that is "simply not open" to consider that there might be any problems with mammography.

"It's is a lot easier to make a simple (and misleading) case for screening, than it is to try to do better. But it is not in the best interest of our patients," he said.

Dr. Colin Begg of Memorial Sloan-Kettering Cancer Center of New York said he thinks the study makes a pretty good case for overdiagnosis, but he questions the authors' assertion that the benefits of mammography are small.

"We have had umpteen randomized trials out there that show there is a mortality benefit of about 15 percent," he said.\

Begg said the authors are concerned that women are being encouraged to get mammograms when it may not be in their best interest, but he said all screening tests have risks as well as benefits.

Breast cancer is the second-leading cause of cancer death in women, exceeded only by lung cancer, according to the American Cancer Society.

"I'm assuming most women who get mammograms are vastly more concerned about preventing their death from breast cancer than they are about the false positives of mammography," he said.