New York Times, February 18, 2011
Study of Breast Biopsies Finds Surgery Used Too Extensively
Doctors say a needle biopsy is safer, less invasive and cheaper, and estimate that more than 300,000 women a year are having unnecessary surgery.
By DENISE GRADY
3 years ago I had an "abnormal" mammogram at the radiology department of a supposedly reputable hospital in NJ. It was interpreted as "highly suspicious for malignancy", and if I had chosen to go to a surgeon (as I was advised to do) for my followup I am ONE HUNDRED PERCENT certain I would have had some sort of invasive procedure. However through the advice of a breast cancer surviving colleague, I went to the Montclair Breast Center, where all they do is treat disorders and diseases of the breast. Because of their expertise and experience I was spared anything invasive, costly, and emotionally traumatic. The bottom line is that the radiologists at the hospital who are generalists were wrong in their interpretation and failed to do the study that would have shown them they were wrong. I also want to add that i had to wait FOUR WEEKS for my callback appointment after the initial screening mammogram was read as supposedly suspicious - I never would have even walked out the door at Montclair if there was anything questionable seen on the screening mammo.
I will never go anywhere else for my mammograms and urge women to skip the general radiology option and go to the specialists. Spare yourself grief, stress, and potentially money.
New York Times, February 8, 2011
Lymph Node Study Shakes Pillar of Breast Cancer Care
By DENISE GRADY
A new study finds that many women with early breast cancer do not need a painful procedure that has long been routine: removal of cancerous lymph nodes from the armpit.
The discovery turns standard medical practice on its head. Surgeons have been removing lymph nodes from under the arms of breast cancer patients for 100 years, believing it would prolong women’s lives by keeping the cancer from spreading or coming back.
Now, researchers report that for women who meet certain criteria — about 20 percent of patients, or 40,000 women a year in the United States — taking out cancerous nodes has no advantage. It does not change the treatment plan, improve survival or make the cancer less likely to recur. And it can cause complications like infection and lymphedema, a chronic swelling in the arm that ranges from mild to disabling.
Removing the cancerous lymph nodes proved unnecessary because the women in the study had chemotherapy and radiation, which probably wiped out any disease in the nodes, the researchers said. Those treatments are now standard for women with breast cancer in the lymph nodes, based on the realization that once the disease reaches the nodes, it has the potential to spread to vital organs and cannot be eliminated by surgery alone.
Experts say that the new findings, combined with similar ones from earlier studies, should change medical practice for many patients. Some centers have already acted on the new information. Memorial Sloan-Kettering Cancer Center in Manhattan changed its practice in September, because doctors knew the study results before they were published. But more widespread change may take time, experts say, because the belief in removing nodes is so deeply ingrained.
“This is such a radical change in thought that it’s been hard for many people to get their heads around it,” said Dr. Monica Morrow, chief of the breast service at Sloan-Kettering and an author of the study, which is being published Wednesday in The Journal of the American Medical Association. The National Cancer Institute paid for the study.
Doctors and patients alike find it easy to accept more cancer treatment on the basis of a study, Dr. Morrow said, but get scared when the data favor less treatment.
The new findings are part of a trend to move away from radical surgery for breast cancer. Rates of mastectomy, removal of the whole breast, began declining in the 1980s after studies found that for many patients, survival rates after lumpectomy and radiation were just as good as those after mastectomy.
The trend reflects an evolving understanding of breast cancer. In decades past, there was a belief that surgery could “get it all” — eradicate the cancer before it could spread to organs and bones. But research has found that breast cancer can begin to spread early, even when tumors are small, leaving microscopic traces of the disease after surgery.
The modern approach is to cut out obvious tumors — because lumps big enough to detect may be too dense for drugs and radiation to destroy — and to use radiation and chemotherapy to wipe out microscopic disease in other places.
But doctors have continued to think that even microscopic disease in the lymph nodes should be cut out to improve the odds of survival. And until recently, they counted cancerous lymph nodes to gauge the severity of the disease and choose chemotherapy. But now the number is not so often used to determine drug treatment, doctors say. What matters more is whether the disease has reached any nodes at all. If any are positive, the disease could become deadly. Chemotherapy is recommended, and the drugs are the same, no matter how many nodes are involved.
The new results do not apply to all patients, only to women whose disease and treatment meet the criteria in the study.
The tumors were early, at clinical stage T1 or T2, meaning less than two inches across. Biopsies of one or two armpit nodes had found cancer, but the nodes were not enlarged enough to be felt during an exam, and the cancer had not spread anywhere else. The women had lumpectomies, and most also had radiation to the entire breast, and chemotherapy or hormone-blocking drugs, or both.
The study, at 115 medical centers, included 891 patients. Their median age was in the mid-50s, and they were followed for a median of 6.3 years.
After the initial node biopsy, the women were assigned at random to have 10 or more additional nodes removed, or to leave the nodes alone. In 27 percent of the women who had additional nodes removed, those nodes were cancerous. But over time, the two groups had no difference in survival: more than 90 percent survived at least five years. Recurrence rates in the armpit were also similar, less than 1 percent. If breast cancer is going to recur under the arm, it tends to do so early, so the follow-up period was long enough, the researchers said.
One potential weakness in the study is that there was not complete follow-up information on 166 women, about equal numbers from each group. The researchers said that did not affect the results. A statistician who was not part of the study said the missing information should have been discussed further, but probably did not have an important impact.
It is not known whether the findings also apply to women who do not have radiation and chemotherapy, or to those who have only part of the breast irradiated. Nor is it known whether the findings could be applied to other types of cancer.
The results mean that women like those in the study will still have to have at least one lymph node removed, to look for cancer and decide whether they will need more treatment. But taking out just one or a few nodes should be enough.
Dr. Armando E. Giuliano, the lead author of the study and the chief of surgical oncology at the John Wayne Cancer Institute at St. John’s Health Center in Santa Monica, Calif., said: “It shouldn’t come as a big surprise, but it will. It’s hard for us as surgeons and medical oncologists and radiation oncologists to accept that you don’t have to remove the nodes in the armpit.”
Dr. Grant W. Carlson, a professor of surgery at the Winship Cancer Institute at Emory University, and the author of an editorial accompanying the study, said that by routinely taking out many nodes, “I have a feeling we’ve been doing a lot of harm.”
Indeed, women in the study who had the nodes taken out were far more likely (70 percent versus 25 percent) to have complications like infections, abnormal sensations and fluid collecting in the armpit. They were also more likely to have lymphedema.
But Dr. Carlson said that some of his colleagues, even after hearing the new study results, still thought the nodes should be removed.
“The dogma is strong,” he said. “It’s a little frustrating.”
Eventually, he said, genetic testing of breast tumors might be enough to determine the need for treatment, and eliminate the need for many node biopsies.
Two other breast surgeons not involved with the study said they would take it seriously.
Dr. Elisa R. Port, the chief of breast surgery at Mount Sinai Medical Center in Manhattan, said: “It’s a big deal in the world of breast cancer. It’s definitely practice-changing.”
Dr. Alison Estabrook, the chief of the comprehensive breast center at St. Luke’s-Roosevelt hospital in New York said surgeons had long been awaiting the results.
“In the past, surgeons thought our role was to get out all the cancer,” Dr. Estabrook said. “Now he’s saying we don’t really have to do that.”
But both Dr. Estabrook and Dr. Port said they would still have to make judgment calls during surgery and remove lymph nodes that looked or felt suspicious.
The new research grew out of efforts in the 1990s to minimize lymph node surgery in the armpit, called axillary dissection. Surgeons developed a technique called sentinel node biopsy, in which they injected a dye into the breast and then removed just one or a few nodes that the dye reached first, on the theory that if the tumor was spreading, cancer cells would show up in those nodes. If there was no cancer, no more nodes were taken. But if there were cancer cells, the surgeon would cut out more nodes.
Although the technique spared many women, many others with positive nodes still had extensive cutting in the armpit, and suffered from side effects.
“Women really dread the axillary dissection,” Dr. Giuliano said. “They fear lymphedema. There’s numbness, shoulder pain, and some have limitation of motion. There are a fair number of serious complications. Women know it.”
After armpit surgery, 20 percent to 30 percent of women develop lymphedema, Dr. Port said, and radiation may increase the rate to 40 percent to 50 percent. Physical therapy can help, but there is no cure.
The complications — and the fact that there was no proof that removing the nodes prolonged survival — inspired Dr. Giuliano to compare women with and without axillary dissection. Some doctors objected. They were so sure cancerous nodes had to come out that they said the study was unethical and would endanger women.
“Some prominent institutions wouldn’t even take part in it,” Dr. Giuliano said, though he declined to name them. “They’re very supportive now. We don’t want to hurt their feelings. They’ve seen the light.”
February 9, 2011
Breast Cancer and Lymph Nodes: Q. and A.
By THE NEW YORK TIMES
Béatrice de Géa for The New York Times Denise Grady
An article in Wednesday’s Times describes how a routine procedure for the treatment of early breast cancer — the surgical removal of cancerous lymph nodes from the armpit — has been found unnecessary for many patients. The finding turns 100 years of standard medical practice on its head.
Today the author of the article, Denise Grady, is taking questions about the finding and its implications. Please post your questions in the Comments box below.
Q.
From what I understand, removing even only one or two lymph nodes can result in chronic swelling of the arm. How certain is it that taking fewer nodes will result in a measurable reduction in the risk of developing lymphedema?
— Claudia Boyle, Mount Prospect, Ill.
A.
There is still a risk of lymphedema even after only a few nodes are taken for sentinel biopsy, but the risk is much lower than when many nodes are removed.
Q.
Is there any information on the advisability of not doing the lymph node removal for women who had a mastectomy, chemotherapy and radiation rather than lumpectomy?
— Donna Landerman, Bloomfield, Conn.
A.
The results apply to women whose condition is like those in the study: stage T1 or T2 tumors (less than two inches across), no palpable lymph nodes, no metastases to other parts of the body and no more than two positive lymph nodes on the sentinel node biopsy. A woman with these characteristics who is having a mastectomy and the other treatments would seem to fit the bill, but the ultimate decision has to be made with a surgeon and an oncologist.
Q.
My breast surgeon told me that lymph node ratio is also important, and I’ve seen studies to support it. They’ve shown that a person who has 1 positive lymph node out of 20 removed does better than a person who had 1 out of 5 who does better than the person who had 1 out of 1. This implies that that there is some survival benefit to the patient who has more nodes removed. Can you find out from your sources: what about the studies that show that lymph node ratio is important? Does this new study trump them, and if so why? Also, what about the length of follow-up in this study?
Breast cancer can recur at any time — even 25 years after initial diagnosis. I’m very glad for all these treatments that improve 5-year survival rates, but are they just pushing back our relapses to a later date? If so, the results of this study may be premature. Are they planning to continue following-up on these patients?
— Breast Cancer Patient, NYC
A.
There is evidence that a higher number of positive nodes is associated with a worse outcome, because it may mean that the cancer is more advanced or spreading more quickly. In the past, the number was used to help plan what kind of chemotherapy to give. But the doctors interviewed for the article published on Wednesday said that in most cases nowadays, the number of lymph nodes does not determine the treatment. Women with any positive nodes are advised to have chemotherapy or hormone-blocking treatment, or both, and the chemotherapy is the same regardless of the number of nodes.
As the article states, the researchers considered the follow-up time long enough to detect a difference in local cancer recurrence rates, meaning in the armpit, because those tend to occur fairly early. There was no difference. A local recurrence is not trivial: It would require more treatment, and 20 to 25 percent of women who have local recurrences ultimately die from the cancer.
It is true that cancer can return at any time. More follow-up time would be more reassuring. I don’t know whether there will be continuing follow-up of these women, but I will ask and post the answer.
Q.
My niece has Stage 3C melanoma. She recently had a number of lymph nodes removed. She originally had two nodes removed that were diagnosed as positive. Thereafter, she had additional nodes removed that were negative. Does the data you’ve written about, as it pertains to lymph nodes, translate to specific cancers other than breast cancer?
— Dave Collopy, Hilo, Hawaii
A.
No, the data really applies only to patients with breast cancer, and only to breast cancer patients like the women in the study.
Q.
I am curious about your opinion of reaching a negative conclusion based on a statistical sample. First of all, the type of error that may be associated with such a conclusion — i.e. that there is in fact a difference that was not detected — is typically not controlled and therefore can float to unknown values.
Second, there is little discussion in the newspapers about the fact that your or any metanalysis is no more a guarantee than any initial study, but merely a statistical evaluation of the likelihood of having detected (or not detected) a real effect.
— Dr. S, Valhalla, N.Y.
A.
The New York Times did not reach a conclusion. We are reporting the conclusion that the authors of a peer-reviewed journal article reached, that the editorialist in the journal supported, and that cancer centers are already putting into practice. We did ask two independent experts on medical statistics at two different universities to evaluate the study. They had some quibbles, but nothing serious enough to throw the findings into question. This was not the first study in this area; there have been others in the past, all pointing in the same direction — to the idea that at least some patients can be spared axillary dissection and the serious complications that it can cause.
Q.
I have not seen raised in this discussion the issue of genetic findings related to the familial propensity for breast cancer if that diagnosis is a part of the clinical picture. How are suspected lymphatic involvement and possible surgical intervention influenced by genetic findings? Thank you.
— MJM, Shenandoah Valley, Va.
A.
We asked this question of Dr. Monica Morrow, an author of the study and chief of the breast service at Memorial Sloan-Kettering Cancer Center in Manhattan. Her reply:
Genetic breast cancer doesn’t influence how we treat the nodes. Due to the increased risk of second breast cancers, many of these women chose mastectomy. Women with mastectomy require axillary dissection if the nodes are involved.
Q.
Surgeons have been removing lymph nodes from the armpits of breast cancer patients for 100 years. Why has it taken so long to find out that not every patient needs this surgery?
A.
The procedure is a holdover from the era of the radical mastectomy, before radiation treatment and chemotherapy existed and when the only hope for controlling cancer was to try to cut it all out. Removing lymph nodes became part of the standard of care, because the nodes might harbor cancer cells that could spread around the body.
Before the sentinel node technique was developed, there was no way to find which nodes were most likely to be the ones where cancer cells would land; to be on the safe side, the only thing surgeons could do was to take out as many nodes as possible. Women suffered from side effects, like lymphedema, that could be severe, but the prospect of a cancer recurrence was worse, so doctors and patients alike were afraid of what would happen if the nodes were not removed. Only when it became apparent that the sentinel node biopsy was reliable did it become possible to ask the next question: If just one or two nodes are positive, do they all have to come out? The answer seems to be no.
Part of what makes it possible to leave the nodes alone is that there are now more effective combinations of chemotherapy and radiation, which can wipe out microscopic traces of disease that might be left behind.
Q.
Which women still need to have their lymph nodes dissected?
A.
Surgeons say that the lymph nodes must come out if they are big enough to feel or show up as cancerous on imaging. Surgeons will also remove nodes if there are three or more positive sentinel lymph nodes (sentinel lymph node biopsy is described in the article).
Surprises can also turn up in the operating room, doctors say. Occasionally, the sentinel node biopsy will give a false-negative result, which means failing to find cancer even though it is present. That can happen if, for instance, the sentinel node is very cancerous and the lymphatic vessels that feed it are choked off and do not pick up the dye. Then, the dye may go to a different node, one that does not have cancer. Knowing this is possible — and knowing that the sentinel node biopsy, though highly reliable, is not infallible — surgeons look and feel around in the armpit carefully during the operation and make judgment calls about what to remove and what to leave alone.
Q.
Why are the study findings said to apply only to women who have whole-breast irradiation, and not partial breast irradiation?
A.
Whole-breast irradiation hits part of the armpit, and therefore some of the lymph nodes. This is what the women in the study received, and researchers think it may have wiped out any cancer in the nodes that were left behind. They say they are also unsure about whether the findings would apply to women who have irradiation while lying prone, on their stomachs. In that position, the radiation may not reach the armpit.
Q.
The study findings apply to 20 percent of patients — about 40,000 women a year in the United States, according to your article. What about the other 80 percent?
– Brandon, Berkeley, Calif.
A.
Here is a further explanation: First of all, 20 percent (the estimate of the study’s lead author, Dr. Armando E. Giuliano) refers to 20 percent of all the newly diagnosed cases of invasive breast cancer each year. This does not include noninvasive breast cancer, or DCIS, ductal carcinoma in situ. The total is about 207,000, so 20 percent is roughly 40,000 women. That is about how many women would match those in the study, in terms of tumor status, affected lymph nodes and course of treatment.
To answer the question about the other 80 percent, we need to look at how many women get a breast cancer diagnosis at various stages. The figures from the American Cancer Society indicate that 60 percent of all patients have “localized” breast cancer. That means they do not have affected lymph nodes. They do not have to worry about extensive axillary dissection, as lymph node removal is known; their sentinel node will be clean. Another 33 percent of women have “regional” disease, meaning that the cancer has reached lymph nodes. These are the patients who might match those in the study.
By Dr. Giuliano’s estimate, about two-thirds of these women will match the study criteria, and one-third will not, so for that one-third, about 10 percent of breast cancer patients over all, node dissection may be needed. Another 5 percent of all patients have “distant” disease at the time of diagnosis, meaning the cancer has already spread to organs or bones. I don’t know if lymph node surgery is of use or benefit to women whose disease is already advanced. In the remaining 2 percent of cases, the stage of the disease at diagnosis is not known.
New York Times, September 22, 2010
Mammograms’ Value in Cancer Fight at Issue
A radiologist reviewing mammogram images at the Elizabeth Center for Cancer Detection in Los Angeles. Most health officials recommend the screenings, but experts disagree over their value.
By GINA KOLATA
A new study suggests that increased awareness and improved treatments rather than mammograms are the main force in reducing the breast cancer death rate.
Starting in their 40s or 50s, most women in this country faithfully get a mammogram every year, as recommended by health officials. But the study suggests that the decision about whether to have the screening test may now be a close call.
The study, medical experts say, is the first to assess the benefit of mammography in the context of the modern era of breast cancer treatment. While it is unlikely to settle the debate over mammograms — and experts continue to disagree about the value of the test — it indicates that improved treatments with hormonal therapy and other targeted drugs may have, in a way, washed out most of mammography’s benefits by making it less important to find cancers when they are too small to feel.
Previous studies of mammograms, done decades ago, found they reduced the breast cancer death rate by 15 to 25 percent, a meaningful amount. But that was when treatment was much less effective.
In the new study, mammograms, combined with modern treatment, reduced the death rate by 10 percent, but the study data indicated that the effect of mammograms alone could be as low as 2 percent or even zero. A 10 percent reduction would mean that if 1,000 50-year-old women were screened over a decade, 996 women rather than 995.6 would not die from the cancer — an effect so tiny it may have occurred by chance.
The study, published Thursday in The New England Journal of Medicine, looked at what happened in Norway before and after 1996, when the country began rolling out mammograms for women ages 50 to 69 along with special breast cancer teams to treat all women with breast cancer.
The study is not perfect. The ideal study would randomly assign women to have mammograms or not. But, cancer experts said, no one would do such a study today when mammograms are generally agreed to prevent breast cancer deaths. In the study, which is continuing, women were followed for a maximum of 8.9 years. It is possible that benefits may emerge later.
Nonetheless, the new study is “very credible,” said Dr. Barnett Kramer, associate director for disease prevention at the National Institutes of Health.
“This is the first time researchers used real populations to compare the effects of treatment and mammography in the modern era of treatment,” Dr. Kramer said. “It shows the relative impacts of screening versus therapy in an era in which therapy has been improving.”
Dr. Otis Brawley of the American Cancer Society said in a statement that the investigators used “careful methodology.” The society, Dr. Brawley said, “believes that the total body of the science supports the fact that regular mammography is an important part of a woman’s preventive health care.”
Dr. Carol Lee, a radiologist at Memorial Sloan-Kettering Cancer Center and chairwoman of the breast imaging commission of the American College of Radiology, said the new study affirmed that mammography saves lives.
“Mortality from breast cancer is decreasing, and I have to believe that screening mammography has played a part,” Dr. Lee said.
In their study, the investigators analyzed data from all 40,075 Norwegian women who had received a diagnosis of breast cancer from 1986 to 2005, a time when treatment was changing markedly.
In that period, 4,791 women died. And, starting in 1996, Norway began offering mammograms to women ages 50 to 69 and assigning multidisciplinary treatment teams to all women with breast cancer, similar to the teams at many major medical centers in the United States. The question was, Did the program of mammograms and optimal new treatment with coordinated teams of surgeons, pathologists, oncologists, radiologists and nurses lower the breast cancer death rate?
The investigators found that women 50 to 69 who had mammograms and were treated by the special teams had a 10 percent lower breast cancer death rate than similar women who had had neither.
They also found, though, that the death rate fell by 8 percent in women over 70 who had the new treatment teams but had not been invited to have mammograms. And Dr. Kramer said he knew of no evidence that breast cancer was more easily treated in women over 70 than in women ages 50 to 69.
That means, Dr. H. Gilbert Welch of Dartmouth wrote in an additional analysis in an accompanying editorial, that mammography could have reduced the breast cancer death rate by as little as 2 percent, an amount so small that it is not really different from zero.
Two percent is an estimate, Dr. Welch said. But, he said, whatever the effect of mammograms is, “all the signals here are that it is much smaller than we believed.”
Dr. Laura Esserman, a professor of surgery and radiology at the University of California in San Francisco, said it tells her that “if you get the same treatment and the outcome is the same if you find it earlier or later, then you don’t make a difference when you find it early.”
And screening has a cost, Dr. Welch said. Screening 2,500 50-year-olds for a decade would identify 1,000 women with at least one suspicious mammogram resulting in follow-up tests. Five hundred would have biopsies. And 5 to 15 of those women would be treated for cancers that, if left alone, would have grown so slowly they would never have been noticed.
When the study was planned, the scientists expected that screening would be even more effective than it was in studies from decades ago. After all, mammography had improved and, in Norway, each mammogram was independently read by two radiologists, which should make it less likely that cancers would be missed. The researchers expected mammograms to reduce the breast cancer death rate by a third.
“We were surprised,” said Dr. Mette Kalager, the lead author of the paper who is a breast surgeon at Oslo University and a visiting scientist at the Harvard School of Public Health.
Marvin Zelen, a statistician at the Harvard School of Public Health and the Dana-Farber Cancer Institute, who was a member of the research team said even though the mammography benefit is small, if he were a woman he would get screened.
“It all depends on how you approach risk,” Dr. Zelen said. His approach, he says, is “minimax” — he wants to minimize the maximum risk — which, in this case, is dying of a cancer.
Dr. Kalager came to the opposite conclusion. She worries about the small chance of benefit in light of the larger chance of finding and treating a cancer that did not need to be treated.
“Since I’m a breast cancer surgeon, I know what being treated is like,” she says. The decision to be screened, she says, “is a matter of personal preference. Is it worth it to risk becoming a patient without it being necessary?”
Many women may still want mammograms, she says, and that is fine.
“I think we have to respect what women want to do.”
A version of this article appeared in print on September 23, 2010, on page A1 of the New York edition.
New York Times, September 29, 2010
Mammogram Benefit Seen for Women in Their 40s
By GINA KOLATA
Researchers reported Wednesday that mammograms can cut the breast cancer death rate by 26 percent for women in their 40s. But their results were greeted with skepticism by some experts who say they may have overestimated the benefit.
The study’s authors include Dr. Stephen Duffy, an epidemiologist at the University of London, and Dr. Laszlo Tabar, professor of radiology at the University of Uppsala School of Medicine in Sweden, who have long been advocates of mammography screening. Their paper is published online in the journal Cancer and will be presented on Friday at a meeting sponsored by the American Society for Clinical Oncology and five other organizations.
The study’s conclusions contrast with those of a report last year by the United States Preventive Services Task Force, an independent group that issues guidelines on cancer screening, questioning the benefit of screening women younger than 50.
The new study took advantage of circumstances in Sweden, where since 1986 some counties have offered mammograms to women in their 40s and others have not, according to the lead author, Hakan Jonsson, professor of cancer epidemiology at Umea University in Sweden.
The researchers compared breast cancer deaths in women who had a breast cancer diagnosis in counties that had screening with deaths in counties that did not. The rate was 26 percent lower in counties with screening.
The study, said Dr. Jennifer C. Obel of the oncology society, “captured the real-world experience of mammograms in this age group.” She suggested that all women, starting at age 40, should “speak to their doctors about mammograms.”
Other experts were not convinced. One problem, said Dr. Peter C. Gotzsche of the Nordic Cochrane Center in Copenhagen, a nonprofit group that reviews health care research, is that the investigators counted the number of women who received a diagnosis of breast cancer and also died of it. They did not compare the broader breast cancer death rates in the counties.
It is an important distinction, Dr. Gotzsche said, because screening finds many cancers that do not need to be treated or found early. With more harmless cancers being found in the screened group, it will look like the chance of surviving breast cancer is greater in that group. “The analysis is flawed,” he said.
Dr. Jonsson said the aim of screening “is to find breast cancers early and to reduce mortality from breast cancer.” He and his colleagues plan to look at the overdiagnosis later, he said.
But Donald Berry, a statistician at MD Anderson Cancer Center, said the overdiagnosis problem was a serious one. “We are finding cancers that would never be found if we didn’t look,” he said. “Small wonder people think screening is great — some of the cancers it finds were not lethal in the first place.”
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.”