New York Times, June 8, 2010
Findings May Alter Care for Early Breast Cancer
By ANDREW POLLACK
CHICAGO — For many women with early-stage breast cancer, treatment may become considerably less arduous, researchers say.
A new study found that certain women getting a lumpectomy may not need an operation to remove underarm lymph nodes, a procedure that can leave them with painfully swollen arms. Compared with not removing the nodes, the surgery did not prolong survival or prevent recurrence of the cancer.
And a second study found that a single dose of radiation, delivered directly to the site of the tumor right after a woman has a lumpectomy, was as effective as the six or so weeks of daily radiation treatments that most women now endure.
“We’re now getting really good long-term survival for breast cancer,” said Michael Baum of University College London, the lead investigator of the radiation study, which was presented here at the annual meeting of the American Society of Clinical Oncology. “The theme is now how can we improve the quality of life for women.”
There is some controversy about whether women should be treated at all for certain early breast abnormalities that some experts say may never hurt them. But if a woman is to be treated, doctors would agree the treatment should be as painless and convenient as possible while retaining effectiveness.
Removal of the underarm lymph nodes next to a cancerous breast was long the standard treatment. In the 1990s doctors began to remove and examine only the sentinel node, the one to which cancer would be likely to spread first. Usually the other nodes are removed only if cancer is found in the sentinel node, which happens in about one quarter of cases.
The more extensive removal, called axillary node dissection, can cause restricted mobility of the arm and painfully swollen arms or fingers.
The study presented here involved 991 women who had had lumpectomies, radiation therapy and a positive sentinel lymph node. Half had the other lymph nodes removed and the others did not.
After five years there was no difference in survival or disease recurrence between the two groups. Some 82.2 percent of the women who had the dissection were alive and disease free compared with 83.8 percent of those who did not. Cancer recurred in the breast or nearby in 4.3 percent of those who had the operation and 3.4 percent in those who did not.
“The evidence is overwhelming that the operation might not be necessary,” the lead investigator, Dr. Armando Giuliano of the John Wayne Cancer Institute in Santa Monica, Calif., said.
About a quarter of women had cancer in the nodes other than the sentinel one, based on the results from those who had the nodes removed. But somehow, this residual cancer did not hurt the patient. That is perhaps because of the radiation the women received. For that reason, Dr. Giuliano said, the results of the study apply only to women who undergo a lumpectomy followed by radiation, not women who undergo complete breast removal, who do not typically get radiotherapy.
One shortcoming was that the trial enrolled only about half the number of patients intended, limiting its ability to draw conclusions. Dr. Giuliano said doctors and patients were reluctant to participate because they feared forgoing node dissection would endanger lives.
Dr. Jennifer K. Litton, a breast cancer specialist at the M. D. Anderson Cancer Center in Houston, said the results could change practice but added, “I don’t think this is going to change overnight.”
She said the study involved only women with tumors that had a relatively favorable prognosis and longer follow-up was needed because cancer can recur after five years.
The radiation study tested a procedure that uses a probe to deliver a high dose of radiation directly into the breast where the tumor has been removed by lumpectomy and while the woman is still under anesthesia. Some women undergo a mastectomy instead of more limited breast-conserving surgery because they do not want the weeks of radiation therapy or live too far from a radiation center.
Dr. Dennis R. Holmes of the University of Southern California, who was one of the investigators in the trial, said one of his patients ran a marathon two weeks after getting the one-time shot of radiation. “That would have been very unlikely in someone receiving standard breast radiotherapy,” he said.
The study involved 2,232 women. After about four years, there were six recurrences within the affected breast in the women who received the single-dose, or intraoperative, radiation and five cases among those who received conventional radiotherapy.
Statistically, the experimental procedure was “non-inferior” to the standard practice. The frequency of major toxicity was similar in the two groups, the authors reported in The Lancet, which published the study online on Saturday. The trial was designed by academic investigators and mainly paid for by University College London Hospitals and the British and German governments. Carl Zeiss, the company that makes the machine used, picked up some expenses. Dr. Baum, the lead investigator, is a consultant to the company.
Dr. Bruce G. Haffty, chairman of radiation oncology at the Robert Wood Johnson Medical School in New Jersey, said “the follow-up isn’t as long as you’d like it to be.” He said cancer can recur after four years and a large dose of radiation can cause tissue damage that might not show up for three to 10 years.
New York Times, December 29, 2009
Old Ideas Spur New Approaches in Cancer Fight
By GINA KOLATA
Mina Bissell will never forget the reception she got from a prominent scientist visiting Lawrence Berkeley National Laboratory, where she worked. She gave him a paper she had just published on the genesis of cancer.
“He took the paper and held it over the wastebasket and said, ‘What do you want me to do with it?’ Then he dropped it in.”
That was 20 years ago, and ever since, Dr. Bissell and a few others have struggled for acceptance of what seemed a radical idea: Gene mutations are part of the process of cancer, but mutations alone are not enough. Cancer involves an interaction between rogue cells and surrounding tissue.
The idea seemed messy and unduly complicated. And cancer genes seemed comparatively clear-cut. So it was often ignored or dismissed as researchers focused on genes and on isolated cancer cells growing in Petri dishes in laboratories.
Now, though, more and more researchers are plunging into those murky depths, studyingtumors in their cellular environments. And, once they do, they say, they can explain many anomalies of cancer. The new focus on a cancer’s surroundings, researchers say, is a major shift in thinking about why cancer occurs and how to stop it.
As yet, the research has not led to cures, and scientists expect the real fruits of their efforts — if they occur at all — will be years in the future.
But as the war on cancer drags on, nearly 40 years after it began, scientists say new directions are urgently needed. The death rate has barely budged for most cancers, and the gene mutation strategy has so far had a limited effect. That is probably because cancer cells have so many genetic abnormalities. If one mutated gene is attacked, others take over.
So some researchers are taking a fresh look at ideas that were dismissed as folklore — a blow to the breast might spur cancer, an infection might fuel cancer cells, a weak immune system might let cancer spread. They also say the new approach may help explain mysteries, like why the breast cancer rate plummeted when women stopped taking menopausal hormones. One answer may be that hormone therapy changes normal cells of the breast and may allow some tiny tumors to escape from the milk ducts where breast cancer starts.
The basic idea — still in the experimental stages — is that cancer cells cannot turn into a lethal tumor without the cooperation of other cells nearby. That may be why autopsies repeatedly find that most people who die of causes other than cancer have at least some tiny tumors in their bodies that had gone unnoticed. According to current thinking, the tumors were kept in check, causing no harm.
It also may mean that cancers grow in part because normal cells surrounding them allowed them to escape. It also means that there might be a new way to think about treatment: cancer might be kept under control by preventing healthy cells around it from crumbling.
“Think of it as this kid in a bad neighborhood,” said Dr. Susan Love, a breast cancer surgeon and president of the Dr. Susan Love Research Foundation. “You can take the kid out of the neighborhood and put him in a different environment and he will behave totally differently.”
“It’s exciting,” Dr. Love added. “What it means, if all this environmental stuff is right, is that we should be able to reverse cancer without having to kill cells. This could open up a whole new way of thinking about cancer that would be much less assaultive.”
Some companies are taking note. Genentech, for example, is investigating the way some skin, ovarian, colon and brain cancers signal surrounding cells to promote cancer growth. The company has an experimental drug that it hopes might block this signaling.
Others are studying drugs like statins or anti-inflammatory drugs that may act by affecting signals between surrounding cells and cancers. But, says Dr. Robert Weinberg, a cancer researcher at M.I.T., “this is not a clearly articulated scientific agenda, in large part because we still know too little about these signals and how their release is controlled.”
The researchers are cautious. They, more than anyone else, know the blind alleys of cancer research over the past few decades. And no one is suggesting that controlling a tumor’s environment will, by itself, cure cancer.
And they are not discounting cancer-causing genes. But even some who have made their careers studying cancer genes say a tumor’s environment can no longer be ignored.
“I am an unabashed cancer geneticist,” said Dr. Bert Vogelstein, director of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins. “The genetic alterations in the cancer cells are the proximate cause of the malignancy.”
But, Dr. Vogelstein said, “one cannot fully understand that disease unless one understands” the tumor’s environment.
It can be a reciprocal interaction, especially as cancers grow and become more advanced. The surrounding cells might let cancers start, but once they do, cancers appear to change the surrounding cells to help fuel the cancers’ growth.
“This notion is not a flash in the pan that will come and go,” said Dr. Weinberg, who, in 1981, discovered the first human oncogene, a naturally occurring gene that, when mutated, can cause cancer.
And Dr. Bissell is now hailed as a hero, with an award named after her.
“You have created a paradigm shift,” the Federation of American Societies for Experimental Biology wrote in a letter announcing that she had won its 2008 Excellence in Science award.
Struggle for Acceptance
Dr. Barnett Kramer, associate director for disease prevention at the National Institutes of Health, recently discovered a paper that startled him. It was published in the medical journal The Lancet in 1962, about a decade before the war on cancer was announced by President Richard M. Nixon. In it, Dr. D. W. Smithers, then at Royal Marsden Hospital in London, argued that cancer was not a disease caused by a rogue cell that divides and multiplies until it destroys its host. Instead, he said, cancer may be a disorder of cellular organization.
“Cancer is no more a disease of cells than a traffic jam is a disease of cars,” Dr. Smithers wrote. “A lifetime of study of the internal-combustion engine would not help anyone understand our traffic problems.”
Dr. Kramer said: “I only wish I had read this paper early in my career. Here we are, 46 years later, still struggling with issues this author predicted we’d be struggling with.”
Others say the time was just not right for such ideas. They know, they say, because they were excoriated when they advanced them.
Dr. Bissell said she had struggled for decades to find acceptance for her ideas.
She was not alone. In 1975, not long after Dr. Bissell started her work, another scientist published a hard-to-refute seminal experiment that seemed to indicate that cancer cells could become normal in the right environment.
The scientist, Beatrice Mintz of the Fox Chase Cancer Center in Philadelphia, inserted mouse cancer cells into early mouse embryos. The embryos grew into mice with cells from the cancer, a teratocarcinoma, and cells from the original embryo. The cancer cells had certainly been incorporated into the mouse embryo, but they were defanged, developing normally. Yet the same cancer cells will spread and kill an adult mouse if they are injected under the skin or into the abdomen.
“It was a sensational experiment,” Dr. Mintz said.
Dr. Bissell also thought the experiment was sensational. But she wanted to know why cells would become deadly tumors in one location and not another.
At the time, she was working with Rous sarcoma virus, or R.S.V., which causes fatal tumors in chickens when inserted into cells. Then, one of her postdoctoral fellows, Dr. David Dolberg, unearthed papers suggesting that the cancer virus would behave differently in chicken embryos.
They injected the virus into embryos. The old papers were correct.
“That meant that if you put the virus in cells in an embryo, you don’t get cancer,” Dr. Bissell said. “And if you put it in a chicken, you do.”
Dr. Bissell and Dr. Dolberg’s paper — the one the visiting scientist dropped into a wastebasket, thinking it ridiculous and clearly wrong — was published in the journal Nature in 1984. The scientist was not the only one who scoffed, Dr. Bissell said.
She interprets the response to the sociology of science.
“The people who are successful become vested in their ideas,” Dr. Bissell said. “It becomes extraordinarily difficult for new ideas to find their way.”
But, to her, the R.S.V. experiments were a clarion call.
Sleeping Cells Awakened
Next, Dr. Bissell did an experiment that gave some credence to an old idea oft dismissed.
Over and over, doctors and patients tell stories of injuries that seemed to spur a cancer. A blow to the breast, an operation, and suddenly cancer takes off. It may mean nothing, just an effort to explain the seemingly inexplicable.
Yet some stories end up in publications. For example, says Dr. Michael Baum, emeritus professor of surgery at University College London, there is a report of eight men with advanced testicular cancer who had surgery to remove the tumors, followed by “a sudden and dramatic exacerbation of the disease.” Animal studies find similar effects, Dr. Baum says.
And in breast cancer, he says, observations of women whose cancer accelerated after breast surgery as well as mathematical modeling indicates that surgery at the site of a dormant tumor can spur it to grow. In some unusual cases, chronic inflammation, as can happen with hepatitis B and C viruses, for example, is thought to lead to cancer. The current hypothesis is that chronic liver inflammation can disrupt the normal architecture of cells, allowing cancers that might have lain dormant to thrive.
Most likely, if wounding or inflammation has an effect, it happens only under unusual conditions and if tiny cancers are already present at the site of the wound.
That is what happened when Dr. Bissell did an experiment in chickens.
She knew that when she injected a chicken with R.S.V., the cancer-causing virus, the bird would develop a huge tumor at the site of the injection. But Dr. Bissell had injected the virus into the bird’s blood. Why weren’t there tumors everywhere?
She reasoned it through.
“What do we do when we inject?” Dr. Bissell asked. “Well, we make a wound. We injected the virus in one wing and got a huge tumor. What would happen if we injected the virus in one wing and wounded the other wing?”
She tried it. A huge tumor grew where she had injected the virus and another grew on the other wing where she had made the wound.
Researchers are not saying that infections or simple cuts or most cancer operations will cause cancer or make an existing cancer spread. Most likely, if there is an effect, it happens only if tiny cancers are already present at the site of the injury.
“Obviously it’s more than just surgery,” Dr. Love said. “The majority of people who have surgery don’t have a problem.”
But, she said, the findings tell her that if people have a choice of more or less invasive surgery — laparoscopy versus open surgery, for example — they might want to choose the less invasive.
“And I say this as a surgeon who likes to put her hands in and muck around,” Dr. Love added.
Dr. Kramer said that made sense, but added: “Would I avoid operations? No. I don’t think the evidence is good enough.”
A bigger risk than wounding, Dr. Bissell says, is simply aging, in which cell architecture crumbles, which is why people get wrinkles, for example. And it may be why most cancer occurs in older people.
“I think that this is unfortunately a fundamental problem in cancer,” Dr. Bissell said. “Unfortunately, we haven’t discovered what to do about aging.”
One of the great mysteries about breast cancer is what to make of tiny tumors known as ductal carcinoma in situ, or D.C.I.S. They are so small they cannot be felt and so common they account for about a quarter of tumors found with mammograms. But, studies show, most stay in the milk ducts, where they originate, never spreading to the rest of the breast where they can become lethal.
The problem is that doctors cannot tell the dangerous D.C.I.S. tumors from the harmless ones, so they treat all such tumors as if they were dangerous.
Dr. Kornelia Polyak of Harvard Medical School, like many others, thought she could solve the problem. From the start, she thought, dangerous D.C.I.S. might have genes different from those of D.C.I.S. that remains harmlessly enclosed in milk ducts. Dangerous D.C.I.S. would look like invasive breast cancer cells and harmless D.C.I.S. would not.
But, she found, D.C.I.S. cells looked just like cells from aggressive breast cancers — gene expression patterns, mutations and cell maturation patterns were all the same.
“It’s just that one tumor is inside the duct, and the other is outside the duct,” Dr. Polyak said.
“That was surprising,” she added. “Why is it D.C.I.S. if it looks like invasive cancer?”
She looked at cells surrounding D.C.I.S.
The first thing she noticed was that when D.C.I.S. broke free of a milk duct, the duct’s outer layer had broken down. It could be that the duct falls apart because the cancer is bursting out. Or it could be that the cancer is escaping the duct because the outer layer disintegrated — which is what her research showed. As long as the milk duct is intact, D.C.I.S. cells cannot escape.
She also found that when breast tissue is injured, wound healing can destroy the crucial outer layer of ducts, allowing D.C.I.S. to escape. That is what happens in animals, and it is her hypothesis that it happens in humans.
It made her ask about biopsies. They are unavoidable, as she knows, because she recently had one herself. And they cannot be a huge factor in causing cancer or millions of women would be getting breast cancer at the site of their biopsies — and they are not.
Still, she worries. “Frankly, this has not been studied extensively,” Dr. Polyak said. “People don’t like to bring it up.”
A Nudge Over Time
The dream of many cancer researchers is to find a way to prevent a cancer cell’s environment from allowing it to grow. They could then prevent cancer.
And in one situation, they might have accidentally stumbled upon a possible method.
The discovery began with a surprise in 2003, when breast cancer rates in women 50 and older suddenly fell 15 percent, after the rates for all women had steadily risen since 1945. The pattern held in 2004.
The drop was traced to the release of a large federal study in 2002 that reported that Prempro, a hormone therapy for menopause that was supposed to keep women healthy and protect them from heart disease, actually made heart disease more likely and slightly increased the risk of breast cancer.
Sales plunged after the report was released, as millions of women stopped taking the drug.
But cancer is supposed to take years, even decades, to develop. How, some asked, could cancer rates drop so quickly?
Could it be possible that the hormone treatment somehow changed the environment of naturally occurring cancer cells and let them progress?
Dr. Karla Kerlikowske, professor of medicine, epidemiology and biostatistics at theUniversity of California, San Francisco, now believes that is a possibility. A combination of estrogen and progestin, like that in Prempro, may change the structure and activity of breast tissue, Dr. Kerlikowske finds, making breast tissue denser, a condition that has nothing to do with how breasts look or feel. Breast density is a cellular structure seen on mammograms and has long been associated with higher cancer risk.
Her hypothesis is that hormone therapy can give “that little bit of nudge over a long enough period to promote breast cancer,” Dr. Kerlikowske said.
For some cancers destined to be aggressive, she suggests, it probably makes no difference if a woman takes hormones because the cancer will spread anyway. But she thinks that “for the average person, it becomes very important.”
That, of course, makes it even harder to figure out cancer.
“If it was easy,” Dr. Polyak said, “we would have done it already.”
This article has been revised to reflect the following correction:
Correction: December 30, 2009
Because of an editing error, an article on Tuesday about new cancer treatments based on older ideas misspelled part of the name of the university that is home to the Ludwig Center for Cancer Genetics and Therapeutics. It is Johns Hopkins University, not John Hopkins.
The New York Times, September 14, 2009
Risks: Breast Cancer Drugs Bear Health Cautions
By RONI CARYN RABIN
Women who take drugs like raloxifene or tamoxifen can reduce their risk of developing invasive breast cancer by up to half, but they may be at greater risk for potentially serious blood clots, according to a new paper that reviews the risks and benefits of the drugs.Skip to next paragraph
For every 1,000 women who take the medications each year, 7 to 10 fewer cases of breast cancer will develop, researchers said.
But both medications increase the risk of blood clots, with the highest risk for tamoxifen: for every 1,000 women who take tamoxifen each year, four to seven additional cases of blood clots occur, according to the study, which appears this week in Annals of Internal Medicine.
Tamoxifen also increases the risk of endometrial cancer and cataracts.
A third drug, tibolone, which is not approved in the United States but is used elsewhere, was included in the study. It significantly reduces breast cancer risk but increases the risk of strokes in older women, the paper reported.
And all three drugs reduce the risk of fractures.The paper assessed the risks and benefits of the drugs when used by healthy women who have never had breast cancer but are considered at greater risk for the disease.
Most of the data analyzed by the study was drawn from eight large clinical trials.
http://www.nytimes.com/2009/09/15/health/15risk-.html?_r=1&scp=3&sq=breast%20cancer%20&st=cse
The New York Times, August 14, 2009
Screening Could Lead to More Potent Cancer Drugs
By NICHOLAS WADE
Researchers have discovered a way to identify drugs that can specifically attack and kill cancer stem cells, a finding that could lead to a new generation of anticancer medicines and a new strategy of treatment.
Many researchers believe that tumor growth is driven by cancerous stem cells that, for reasons not understood, are highly resistant to standard treatments. Chemotherapy agents may kill off 99 percent of cells in a tumor, but the stem cells that remain can make the cancer recur, the theory holds, or spread to other tissues to cause new cancers. Stem cells, unlike mature cells, can constantly renew themselves and are thought to be the source of cancers when, through mutations in their DNA, they throw off their natural restraints.
A practical test of this theory has been difficult because cancer stem cells are hard to recognize and have proved elusive targets. But a team at the Broad Institute, a Harvard-M.I.T. collaborative for genomics research, has devised a way of screening for drugs that attack cancer stem cells but leave ordinary cells unharmed.
Cancer stem cells are hard to maintain in sufficient numbers, but the Broad Institute team devised a genetic manipulation to keep breast cancer stem cells trapped in the stem cell state.
The team, led by Piyush B. Gupta, screened 16,000 chemicals, including all known chemotherapeutic agents approved by the Food and Drug Administration. The team reported in the Thursday issue of Cell that 32 of the chemicals selectively went after cancer stem cells. These particular chemicals may or may not make good drugs, but the screening system proves, the researchers say, that it is possible to single out cancer stem cells with drugs that leave ordinary cells alone. Only one of the 32 chemicals is approved as a drug for cancer. Another approach to concentrating on cancer stem cells, based on the use of antibodies, was reported this month by OncoMed Pharmaceuticals, a company founded by Michael F. Clarke, a Stanford researcher who in 2003 discovered cancer stem cells in breast tumors.
If effective drugs against cancer stem cells can be developed, one obvious strategy would be to use them in combination with standard chemotherapeutic agents, so that all types of cells in a tumor could be attacked. That way, cancer would be attacked as AIDS is now — with a cocktail of chemicals that blocks all escape paths. Both the AIDS virus and cancer cells can change DNA to dodge an effective drug, but are thought to perish if confronted with many drugs at once.
Standard chemotherapy is effective because the chemicals are applied in such large doses that they kill all cells. But this approach is stressful for the patient.
“You could probably lower the doses considerably with a combination of drugs that attacked specific types of cell,” Dr. Gupta said.
Eric S. Lander, director of the Broad Institute, said: “If we make a drug that kills 99.9 percent of the cells in a tumor but fails to kill the 0.1 percent, that is the real problem. It’s a pyrrhic victory.”
Dr. Lander said that given the new screening system and the idea of using combinations of drugs against cancer, there was “a potential for a real renaissance in cancer therapeutics.”
“We have not been able to do that yet with cancer,” he added, “but if we could, it’s a numbers game, and we win.”
The cancer stem cell theory has been thrust into the spotlight in recent years with the discovery of stem cells in many types of solid tumors, including those of the breast, brain, prostate, colon and pancreas. This month, a Stanford team led by Irving Weissman reported finding the stem cells of bladder cancer.
But the theory is not without critics.
“The cancer stem cell hypothesis has in the past year been challenged on many fronts,” said Bert Vogelstein, a leading cancer geneticist at Johns Hopkins University. “For example, a paper on melanomas last year showed that 100 percent of melanoma cancer cells were cancer stem cells.”
If many of a tumor’s cells are stem cells, then existing chemotherapy agents are clearly killing them, Dr. Vogelstein said, and the cancer stem cell theory is not an effective guide to finding new drugs.
The theory has also aroused opposition because, in its extreme, it implies that standard chemotherapy goes after the wrong targets and is ineffective.
“It’s the most amazing polarity that I’ve seen,” Dr. Clarke, the Stanford researcher, said of the debate over stem cells among cancer researchers. “It’s like two religions fighting.”
Some advocates of the idea believe that to dissolve tumors, it would be necessary to go after only cancer stem cells, if such drugs existed. But the Broad Institute team and others take the view that a combination of drugs attacking each of the types of cells in a tumor would be best.
One reason for using a combination of drugs is the suspicion that mature cancer cells may be able to convert themselves back into stem cells, a route that is apparently prohibited to normal mature cells.
“The possibility is that the nonstem cells in a tumor may regenerate de novo new stem cells,” said Robert Weinberg, a leading cancer biologist at M.I.T. and, a co-author with Dr. Lander of the Cell report. “If one had ways of treating both the stem cells and the nonstem cells, then the de novo generation of stem cells would be dealt with.”
The basic insight of the cancer stem cell theory is that there is a hierarchy of cells in a tumor, with the stem cells at the top generating the mature cells that are the majority. Most researchers accept that this is a good description of leukemias because Gleevec, a highly effective drug for chronic myelogenous leukemia, does not kill stem cells, and the leukemia returns if the treatment is stopped.
But with solid tumors, Dr. Vogelstein said, “the jury is out.” If stem cells are common in solid tumors, not just a small resistant reservoir of cells, “then there’s no difference between the stem cells and the bulk cancer — so a screen for drugs to kill melanoma cells is by definition also going to kill the melanoma’s cancer stem cells.”
Still, in Dr. Vogelstein’s view, the Broad Institute’s new screening method is important whether or not the cancer stem cell theory is correct. “Because most of the compounds in use now clearly aren’t doing the job we’d all like,” he said, “then novel methods for screening could be extremely valuable.”
The Broad Institute researchers hope that pharmaceutical companies will use their screening method to begin to develop drugs against cancer stem cells.
The New York Times, April 22, 2009
Breast-Feeding Benefits Mothers, Study Finds
By RONI CARYN RABIN
Most doctors agree that breast-feeding is best for babies' health. Now a large study suggests that the practice benefits mothers as well: women who have breast-fed, it says, are at lower risk than mothers who have not for developing high blood pressure, diabetes and cardiovascular disease decades later, when they are in menopause.
The benefits increase with duration of past breast-feeding, the study found. Women who had breast-fed for more than a year in their entire lifetimes were almost 10 percent less likely than those who had never breast-fed to have had a heart attack or a stroke in their postmenopausal years. They were also less likely to have diabetes, hypertension and high cholesterol.
The study found that even those postmenopausal women who had breast-fed for just one month had lower rates of diabetes, high blood pressure and high cholesterol, although the risk of heart disease after such limited breast-feeding was comparable to that among mothers who had never breast-fed.
The research, which is to be published in the May issue of the journal Obstetrics & Gynecology, analyzed data on some 139,681 women who had enrolled in the Women's Health Initiative, a long-term national study of postmenopausal women.
Women who reported a lifetime history of more than a year of breast-feeding were 20 percent less likely to have diabetes, 12 percent less likely to have hypertension, 19 percent less likely to have high cholesterol and 9 percent less likely to have had a heart attack or a stroke by the time they enrolled in the Women's Health Initiative.
The new study's chief author, Dr. Eleanor Bimla Schwarz, assistant professor of medicine at the University of Pittsburgh, said of breast-feeding, ''We've known for a long time that it's important for the baby's health, but we now know it's important for mothers' health as well.''
Other experts cautioned, however, that while the study demonstrated an association between breast-feeding and health benefits, there was not necessarily a causal relationship. Women who breast-feed may simply lead more healthful lives than those who do not, these experts said, noting that the new analysis might not have been able to account for all the differences between the two groups.
Breast-feeders ''may be healthier women who take better care of themselves,'' said Dr. Nieca Goldberg, medical director of the N.Y.U. Women's Heart Center.
''This is a nice association,'' Dr. Goldberg said of the findings, ''but we don't know from the study what the physiological mechanism is.''
If there is such a mechanism, Dr. Goldberg suggested, it could lie in oxytocin, a hormone crucial to milk production. Oxytocin is known to relax blood vessels, she said, and may make them more flexible and more resistant to the buildup of plaque.
Breast-feeding is also known to play a role in healing after pregnancy, by causing uterine contractions that help restore the uterus to its original size more quickly. Further, women burn extra calories when making milk, helping them eliminate fat stores accumulated during pregnancy.
Other recent studies have suggested breast-feeding may also reduce the risk of osteoporosis and both breast and ovarian cancer, as well as Type 2 diabetes.
New York Times, February 12, 2009
Bone Drugs May Help Fight Breast Cancer
By GINA KOLATA
A drug of a class commonly used to combat bone loss may reduce by a third the chance that some breast cancers will spread or recur, a large study has found.
While it may sound odd to treat cancer with a drug that acts on bone, evidence is accumulating that such drugs may do more than just prevent the loss of bone. Other studies are testing the drugs in patients with prostate or lung cancer.
The new study, published in Thursday’s New England Journal of Medicine, involved 1,803 premenopausal women with tumors that were fueled by estrogen. As part of their treatment, all received drugs that shut down their ovaries, preventing them from making estrogen, along with drugs that stymie cancer cells from using estrogen to grow.
Half also got the bone drug zoledronic acid, or Zometa, as an intravenous infusion twice a year for three years. Those who took the drug had a 36 percent reduction in cancer recurrences and metastases, compared with women who did not get it. After nearly four years, 54 women who received zoledronic acid and 83 who did not had a recurrence of their cancer or had a new cancer in the opposite breast or a metastasis to their bones.
Some cancer researchers said they wanted to see the results from two other large studies of bone drugs and breast cancer before advocating that all women with breast cancer get such drugs. The studies, which include both premenopausal and postmenopausal women, are nearing completion, and their results should be available within the next few years. But the new study has buoyed researchers’ hopes.
“This is really a landmark study,” said Dr. James N. Ingle, head of the breast cancer research program at the Mayo Clinic Cancer Center. “It’s a reason for real enthusiasm.”
But for now, he said, “I think it is the general consensus that we are not ready to make this a standard treatment.”
Others are more persuaded.
Dr. Marc E. Lippman, a breast cancer expert who is chairman of the department of medicine at the University of Miami, said many women taking hormonal therapy for breast cancer already take drugs to protect their bones. The hormonal therapy deprives the body of the bone-building effects of estrogen. So, he said, why not give these women zoledronic acid, the bone drug used in the study?
“This is something of a mitzvah,” Dr. Lippman said. “The very therapy you might want to do to counteract the toxicity” of the hormonal therapy “has an additional advantage.”
“I think you have to give it,” he said.
The idea of using a drug like zoledronic acid arose from research into why some cancers, like breast cancers, have a predilection to spread to bone.
One reason, Dr. Ingle said, is that cancer cells interact with a type of bone cell, osteoclasts, whose role is to break down bone. Breast cancer cells that migrate to the bones stimulate osteoclasts. Osteoclasts then produce substances that stimulate the cancer cells.
“You get this vicious cycle,” he said.
Drugs used to treat osteoporosis, the bone-thinning disease that often occurs in the elderly, home in on osteoclasts and stop them from releasing substances that cause bone loss. As the osteoclasts stop working, they die.
So the idea arose: Perhaps osteoporosis drugs might prevent cancer cells from growing in bones.
Other studies of the osteoporosis drugs, known as bisphosphonates, indicated that they might also have other anticancer effects. In the laboratory, at least, they stopped cancer cells from growing new blood supplies. And bisphosphonates made cancer cells self-destruct in laboratory studies.
In addition, said Dr. Eric P. Winer, a breast cancer specialist at the Dana-Farber Cancer Institute in Boston, still other studies indicated that bisphosphonates affected how well cancer cells stuck to surrounding tissue and whether they were able to invade other tissue and proliferate.
And, said Dr. Michael Gnant of the Medical University of Vienna, the lead author of the new study, recent research indicates that particularly in the early stages of many cancers, there is a population of tumor cells that migrate to the bones and hide in bone marrow. Bisphosphonates, he said, might squelch those cells, affecting the ability of the disease to recur.
“This is a general mechanism for all cancers,” Dr. Gnant said. “Not just cancers that metastasize to bone.”
The idea for the cancer studies began when researchers, like Dr. Trevor J. Powles, a professor of breast oncology at Parkside Oncology in London, started asking whether bisphosphonates could treat cancer that had already spread to bone. They could, it turned out, and zoledronic acid and other bisphosphonates were subsequently approved for that use and shown to prevent further spread of cancer in bones. In fact, Zometa is approved only for bone complications of cancer, like fractures — it is not licensed as an osteoporosis drug.
Those discoveries led Dr. Powles and his colleagues and, independently, two other groups of researchers, to ask whether the drugs, in the high doses used to treat cancer, might prevent breast cancer from spreading in the first place.
The results, published a few years ago, were mixed. Dr. Powles’s study found that when women took a bisphosphonate their cancer was less likely to spread to their bones and they lived longer. Another study also found that the cancer was less likely to spread. But the third study found no effect.
Dr. Gnant, in the meantime, had begun a much larger study with intravenous zoledronic acid at a much lower dose, given twice a year for three years. The concern with the drug is a rare and very serious side effect, osteonecrosis of the jaw. But in this study at least, it did not occur.
And the surprising result of his study, if it holds up, indicates that zoledronic acid could add a benefit to existing breast cancer therapy that is nearly the same magnitude as the benefit conferred by chemotherapy or hormonal therapy alone.
But Dr. Gnant urges caution.
“While everyone is very excited, we still need to be conservative about what we recommend to patients,” he said. “In clinical science we do clinical trials. I am still hesitating to say, ‘Well, this is good for everyone.’ In the history of science we sometimes extrapolated and turned out to be absolutely wrong.”
“The right way to proceed,” Dr. Gnant said, “is to wait for data to come in from other studies.”