By Sherry Baker
HealthDay Reporter
Tuesday, March 11, 2008
TUESDAY, March 11 (HealthDay News) -- There's good news for the 60 percent of women with breast cancer whose malignancies are estrogen-driven: Researchers say taking the aromatase inhibitor (AI) drug letrozole (Femara) can cut risk of a recurrence by more than half.
That benefit was seen even when women initiated the drug one to seven years after they stopped treatment with the anti-estrogen drug tamoxifen, the study found.
In other findings, letrozole lowered the risk of breast cancer metastasis by 61 percent, according to the researchers. The drug also reduced the odds of a tumor forming in a breast that was initially cancer-free by more than 80 percent, said a team reporting in the April issue of theJournal of Clinical Oncology.
"We were expecting letrozole to work from the earlier, initial results, but the actual magnitude of benefit was a bit surprising. For any woman who has had hormone-sensitive breast cancer in the past, our results show a big reduction in recurrence if letrozole is initiated any time between 1 and 7 years after 5 years of tamoxifen -- that's up to 12 years after diagnosis," said lead researcher Dr. Paul E. Goss, director of Breast Cancer Research at Massachusetts General Hospital Cancer Center, Boston.
The findings are expected to be applied immediately to receptor-positive breast cancer treatment, Goss said.
There was one slight down side to letrozole therapy: Just over 5 percent of the 1,500 women taking the drug reported a new diagnosis of osteoporosis or bone fracture, compared to about 3 percent of 800 study participants who were not on the regimen, the researchers said.
Tamoxifen, which blocks estrogen receptor cells, is standard adjunct treatment for estrogen-sensitive cancers, but the benefits of the drug drop significantly after five years. Aromatase inhibitors block the other, less potent sources of estrogen in the body by keeping androgens from the adrenal glands and other tissues from transforming into estrogen.
The current study was based on data collected from the original MA.17 trial, conducted through the National Cancer Institute of Canada and also led by Goss. MA. 17 was designed to study whether letrozole could reduce tumor recurrence and increase survival in breast cancer patients after five years of tamoxifen treatment.
In October of 2003 , the study was ended a year earlier than originally planned when preliminary data showed that women taking letrozole were significantly less likely to have a cancer recurrence. Study participants in the placebo arm were offered letrozole when the study was halted. According to Goss, that gave the researchers the opportunity to compare the recurrence rates in women from the placebo group who chose to take the AI with those who decided on no further treatment.
Based on the new findings, "we believe every patient who has previously taken tamoxifen should discuss the findings of this study with her oncologist. Our results suggest if you take anti-estrogen, aromatase inhibitor therapy at any point of diagnosis, it is going to impact your chances of not experiencing a recurrence," Goss said.
Another expert agreed that the findings are significant.
"This study shows that the hormonal driving pathways continue to be very active after the tamoxifen has ended. And, the fact you've got a 60 percent improvement in disease-free survival with the addition of letrozole is a very powerful argument for its inclusion in treatment," said Dr. Brian Leyland-Jones, executive director of the Winship Cancer Institute at Emory University in Atlanta.
"The only imperfection of this trial, in terms of its design, is that it was not randomized -- patients chose whether or not to continue on letrozole," Leyland-Jones said. "And the only negative note is the risk of osteoporosis and increased risk of fractures for those who switched to letrozole. So, the news is very good but not all perfect."
More information
SOURCES: Paul E. Goss, M.D, Ph.D., director, Breast Cancer Research, Massachusetts General Hospital Cancer Center, Boston; Brian Leyland-Jones, M.D., Ph.D., executive director, Winship Cancer Institute, Emory University, Atlanta; April 2008,Journal of Clinical Oncology
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FDA FINALLY APPROVES AVASTIN
February 25, 2008
(
Last year, specialists convened to determine the effectiveness of Avastin as a breast cancer treatment for the FDA. Although results did show minimal slowing in growth of the tumors by using Avastin, the drug failed to improve patient condition or to diminish the cancerous tumor entirely. Subsequently they voted 5 to 4 against the approval of Genetech’s request and provided the results of their study to the FDA with their recommendation.
“All they had was progression-free survival in one trial, no increase in quality of life and patient deaths in the Avastin group,” said Fran Visco, President of National Breast Cancer Coalition. “We’re very confused why the FDA made this decision.”
Health experts fear that the decision made by the FDA to approve Avastin with very little proof of affectivity could set as precedence for other pharmaceutical companies with similar products to push for approval by the bureau thereby lowering the standards of breast cancer treatment in the market from the initial object of complete recovery to merely survival.
“If the FDA sets a precedent of approving a drug based on progression free survival, people are afraid they may stop looking at survival as the most important endpoint,” said Dr. Kay Dickersin, director of the Center for Clinical Trials at
Meanwhile, the Breast Cancer Organization was optimistic of Avastin’s approval for breast cancer treatment as a new option for patients. “The benefits we’re looking at here matter because they give patients hope,” said Margaret C. Kirk, the group’s chief executive. “Without disease progression they may survive to see a discovery that can help them.”
http://www.newsli.com/2008/02/25/fda-approves-avastin-as-breast-cancer-drug/
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CUT-OFF CANCER PATIENT TO GET $9MILLION IN DAMAGES
By Thomas Watkins – Associated Press 2/25/08
LOS ANGELES (AP) — A woman who had her medical coverage canceled as she was undergoing treatment for breast cancer has been awarded more than $9 million in a case against one of California's largest health insurers.
Patsy Bates, 52, a hairdresser from
On Friday, arbitration judge Sam Cianchetti ordered Health Net to repay that amount while providing $8.4 million in punitive damages and $750,000 for emotional distress.
"It's hard to imagine a situation more trying than the one Bates has had to endure," Cianchetti wrote in the decision. "The rug was pulled out from underneath, and that occurred at a time when she is diagnosed with breast cancer, one of the leading causes of death for women."
Bates, a mother of two, said she screamed when she heard about the damage award.
"I am elated," she said.
Bates' attorney William Shernoff said he wanted other insurers to take notice of the award.
"We are going to put a stop to this practice," he said.
Health Net said it was implementing a freeze on policy cancelations that would last until the company sets up a third-party review panel to scrutinize cases.
"Obviously we regret the way that this has turned out, but we are intent on fixing the processes to maintain the public trust," spokesman David Olson said.
The award came a day after the
Health Net acknowledged that such a program existed in 2002 and 2003 but was subsequently scrapped.
"It's hard to imagine a policy more reprehensible than tying bonuses to encourage the recision of health insurance that helps keep the public well and alive," Cianchetti wrote in the Bates decision.
Bates had been insured with another company but was persuaded to switch over to a Health Net policy after an agent suggested she could save money.
She said she had undergone surgery to remove a tumor and had received her first two chemotherapy treatments when doctors stopped treating her because her bills were going unpaid.
"I was devastated. I didn't know what was going to happen," Bates said. "It's boggling that someone can do that to you."
Bates went on to complete her cancer treatment through a state-funded program.
Health Net also said it would review its practices and the way its brokers and agents are trained.
http://ap.google.com/article/ALeqM5jf3kOQZF8y9J9WqUVv0NCuUHA_OgD8V07A204
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MORE PROOF
STUDY: EXERCISE INCREASES BREAST CANCER
SURVIVAL RATE
Anita Weier — 2/25/2008
Women who exercise after a breast cancer diagnosis can improve their chances of survival, according to a study by researchers at several universities and cancer centers, including UW-Madison.
The six-year study indicated women with breast cancer who engaged in moderate to vigorous exercise had a 35 to 49 percent decreased risk of dying from the disease. Women who had the most physical activity had higher survival rates than those with the lowest level.
A research team including investigators from the University of Wisconsin School of Medicine and Public Health made the findings in a study published in the February edition of Cancer Epidemiology Biomarkers & Prevention.
"The results suggest that women with breast cancer who exercise are more likely to survive longer than women who are less active," said epidemiologist Amy Trentham-Dietz, a
She also published a separate study last year showing that women who are active have a lower risk of developing breast cancer.
In the new study, researchers surveyed about 4,500 participants from
The principal researchers were Crystal Holick, an epidemiologist formerly from the
Holick said that the new findings back up Trentham-Dietz's previous research and show that being active is important for women as a long-term lifestyle choice. The American Cancer Society also recommends 30 minutes of moderate activity at least five days a week.
The study was funded through grants from the Susan G. Komen Breast Cancer Foundation, the Avon Foundation and the National Cancer Institute.
http://www.madison.com/tct/news/274162
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CALLING ALL
SURVEY ON BREAST CANCER CARE
Breast Cancer Care is calling on people in communities across
The findings of the questionnaire will identify key issues for those affected by breast cancer, and help influence and develop the charity's policy and campaign agendas in
Anna Wood, Head of Policy and Campaigns at Breast Cancer Care, the
"Some of the questions also touch upon the future of healthcare, which will enable us to determine which areas of concern need to be raised with policy-makers and the Government.
"This really is your chance to have your say on the development of future breast cancer treatment, information and services.
"It's important that we get as many responses as possible to give us a clear picture of the current situation. So whatever your experience of breast cancer, please take the time to complete this important survey."
The survey is divided into sections relating to treatment, care, information and support. However, these themes are not exhaustive and people will have the chance to raise any issues that are not addressed in the questionnaire.
To receive a copy of the survey either log on to www.breastcancercare.org.uk and follow the Campaigning links or call Laura Brandon, Campaigns Officer at Breast Cancer Care, on 0207 960 3458.
http://www.thisiswiltshire.co.uk/news/headlines/display.var.2069652.0.survey_on_breast_cancer_care.php
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MUSHROOM COMPOUND BOOSTS EFFICACY OF BREAST CANCER DRUGS
By David Liu, Ph. D.
SUNDAY FEB 24, 2008 (Foodconsumer.org) -- A compound found in Chinese medicinal mushroom Coriolus versicolor may help enhance efficacy of certain breast cancer drugs, according to a new Chinese study published in the March 2008 issue of International Journal of Oncology.
The researchers from the
Earlier the researchers have found this compound was able to enhance the cytotoxicity of certain S-phase targeted-drugs on human leukemic HL-60 cells via some cell-cycle and apoptotic-dependent pathways.
In the current study, breast cancer cells treated with the PSP had a longer DNA synthesis time, suggesting that the compound boosted the apoptotic effect of Doxo and VP-16 via creating an S-phase trap in the human breast cancer cell line ZR-75-30.
Wan JM and colleagues conclude in their study report "the anticancer potentials of PSP is not limited to leukemia but may also be used as an adjuvant therapy for breast cancers."
http://foodconsumer.org/7777/8888/C_ancer_31/022406532008_Polysaccharopeptide_enhance_efficacy_of_breast_cancer_drugs_printer.shtml
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SHEDDING LIGHT ON A CAUSE OF BREAST CANCER
February 21, 2008 01:31 PM ET | Ben Harder
Brightly lit communities have high rates of breast cancer, according to a new study of cancer data and satellite images of light pollution.
Brightly lit communities have high rates of breast cancer, according to a new study of cancer data and satellite images of light pollution.
When
Consider some of the evidence: Blind women have low rates of breast cancer. So do women in underdeveloped countries, where artificial lighting is an uncommon luxury. By contrast, female nurses and other women who frequently work night shifts have high breast cancer rates. The reason, experts believe, is that their schedules expose them to illumination during what should be the darkest hours of their days, and that disrupts the body's production of the cancer-suppressing hormone melatonin. In lab experiments, human breast tumors have been found to grow relatively quickly when fed by the blood of women who have been in a brightly lit room in the middle of the night. When blood is drawn from women who've been sitting in darkness, it's richer in melatonin and less nourishing to the cancer.
Based on those and other observations, a unit of the World Health Organization announced in December that shift work is a "probable human carcinogen." But shift work may be merely the tip of
In fact, any woman whose community is filled with streetlamps and other light sources may face an unnaturally high risk of breast cancer. A new study, slated to appear in the journal Chronobiology International, finds that breast cancer incidence is about 73 percent higher in communities with the greatest amount of artificial light at night than in communities with the least. The researchers assessed different communities' nocturnal light levels by analyzing satellite images of how much illumination escapes into space. (You can see this Washington Post article for details.)
Light pollution seems to have other untoward consequences, including harmful effects on animals like migratory birds and sea turtles. But the apparently carcinogenic effects of light pollution have received—and arguably deserve—the lion's share of scientists' attention. No one has paid more notice to the light-cancer connection than Richard Stevens, the University of Connecticut Health Center epidemiologist who first proposed a possible link more than two decades ago. Stevens collaborated on the new study with four colleagues in
He was quick to say that the study falls short of proving cause and effect. But it's consistent, he said, with the hypothesis that light at night accounts for a "substantial fraction of breast cancer."
"Lighting the night is as important an ecological issue for the planet as global warming," he added. "In addition to its effects on all life forms, unnecessary lighting of the night accounts for a lot of fossil fuel consumption and also contributes to global warming."
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DETECTING BREAST CANCER EARLY
DOCTORS CATCH CANCER EARLIER WITH SPECIAL MRI
January 1, 2006 — A new kind of MRI machine helps doctors diagnose breast cancer earlier. Patients lie on their stomach and their breasts are placed in two coils, which focus radio waves and allow for more complete images that give a three-dimensional look inside the breast.
Two-hundred thousand women will be diagnosed with breast cancer this year in the
Suzette Lipscomb knows how to get the most out of every moment and she plans to share most of those moments with her little girl, Ava. "I always wanted a little girl, but I was a little afraid that I may pass on some type of tendency toward the disease," Suzette says.
The disease she feared? Breast cancer. Her grandmother beat it and so did she. It wasn't easy though, during her battle she was forced to make a difficult decision. Suzette says, "I was trying to make a decision as to whether or not to remove both my breasts."
Richard Reitherman, a breast radiologist at CAD Imaging Sciences in
"She and her surgeon know exactly how big the tumor is, so it gives her the best treatment," Dr. Reitherman says. For Suzette it showed her second breast was clear.
A dye injected into the patient helps pinpoint cancer and if chemotherapy treatments are working. In the scan, the red areas are cancer -- cancer that was missed in a mammogram. In fact, 20 percent of women who don't have the cad-sciences MRI will need a second surgery, something Suzette was able to avoid.
"I feel like the luckiest woman alive that not only did I have my cancer caught early enough that I'm alive, but that I was able to have a child," Suzette says.
Not all women are candidates for this cadsciences MRI. It's used for women who have already been diagnosed and need to know a course of action. It's also used for women who are high risk and have a family history of the disease. The procedure takes about 30 minutes; results are available 15 minutes later.
BACKGROUND: Women have a new imaging tool set to help diagnose breast cancer. The 3TP method generates a unique color-coded map by measuring changes (color and intensity) in contrast agent concentration in normal and cancerous tissues over time. It provides information that is not readily available from traditional mammography or MRI. In addition, the 3TP system is ergonomically designed to be comfortable for the patient, regardless of breast size.
HOW MRI WORKS: Magnetic resonance imaging uses radiofrequency waves and a strong magnetic field instead of X-rays to provide clear and detailed pictures of internal organs and tissues. These radio waves are directed at protons in hydrogen atoms -- one of the most abundant atoms in the human body, because of the body's high water content. The waves "excite" the protons, and when they "relax," they emit strong radio signals. A computer can turn those signals into a high-contrast image showing differences in the water content and distribution in various bodily tissues. It is becoming increasingly popular as an alternative to traditional X-ray mammography for the early diagnosis of breast cancer because women aren't exposed to the same radiation they experience with X-rays.
ABOUT BREAST CANCER: Breast cancer is a type of cancer in which cells in the breast become abnormal and grow and divide uncontrollably, eventually forming a mass called a tumor. Some tumors are benign, meaning that they do not invade other types of tissue, although if they become big enough, they can interfere with some bodily functions, such as the flow of blood or urine. Malignant tumors have cells that can invade nearby tissues. When a cancer "metastasizes," cells from the original tumor break off and travel to other parts of the body via the blood or lymph systems. More than 75 percent of breast cancers begin in the milk ducts within the breast. The next most common site is in the glandular tissue that makes the milk.
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CHICKEN ANITOBODIES TO HELP DETECT HER2
BREAST CANCER
ScienceDaily (Feb. 25, 2008) — Generations of mothers have served up chicken soup to remedy the common cold, but now the therapeutic fowl may find use in diagnosis as well. Researchers at the National Institute of Standards and Technology (NIST), the National Cancer Institute (NCI) and the scientific research firm SAIC recently showed how chicken antibodies may one day improve the detection of an aggressive form of breast cancer.
HER2 is one of a family of genes that help regulate the growth and proliferation of human cells. Normal cells have two copies of HER2, but about 20 to 25 percent of breast cancers have multiple copies of the gene, resulting in the overproduction of a HER2-encoded protein (called HER2) that stimulates tumors to be particularly fast growing and difficult to treat in a subset of breast cancer patients.
Patients with that form of breast cancer--about 40,000 women in the
In a paper in the International Journal of Cancer,* the NIST-NCI-SAIC research team found that chicken immunoglobulin Y (IgY) antibody created against the HER2 protein could be tagged with quantum dot (tiny, intense and tunable sources of colorful light) to more reliably detect the HER2 biomarker than the existing diagnostic tests using mammalian antibodies tagged with conventional fluorescent dyes. Overall, the improvement in sensitivity to the HER2 biomarker was about 40-50 percent.
The increased sensitivity of the HER2 quantum dot-based quantitative bioimaging system stems from the broad genetic differences between avian and human species. The chicken IgY antibody to HER2 reacts strongly with the target protein while ignoring other human proteins that can interfere with current diagnostic tests.
Other advantages of the novel NIST-NCI-SAIC system include faster and larger-scale production of the antibodies and a more reliable quantitative measure of HER2 biomarker level, in part because the quantum dot tags will stay bright and detectable while fluorescent dyes fade over time.
The research was funded under an interagency agreement between NIST and NCI. NIST also is funding the development of a standard reference material to support HER2 testing.
* Y. Xiao, X. Gao, G. Gannot, M.R. Emmert-Buck, S. Srivastava, P.D. Wagner, M.A.Amos and P.E. Barker. Quantitation of HER2 and telomerase biomarkers in solid tumors with IgY antibodies and nanocrystal detection. International Journal of Cancer, posted online Jan. 23, 2008.
Adapted from materials provided by National Institute of Standards and Technology.
http://www.sciencedaily.com/releases/2008/02/080219203526.htm
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GENE PROFILING PREDICTS RESISTANCE TO BREAST CANCER DRUG HERCEPTIN
ScienceDaily (Feb. 21, 2007) — Using gene chips to profile tumors before treatment, researchers at Harvard and Yale Universities found markers that identified breast cancer subtypes resistant to Herceptin, the primary treatment for HER2-positive breast cancer. They say this advance could help further refine therapy for the 25 to 30 percent of breast cancer patients with this class of tumor.
In the February 15 issue of Clinical Cancer Research, the researchers found that HER2-positive tumors that did not respond to Herceptin expressed certain basal markers, growth factors and growth factor receptors. One of these, insulin-growth factor receptor 1(IGF-1R), was associated with a Herceptin response rate that was half that of tumors that did not express IGF-1R.
They also discovered that resistant tumors continue to over-express the HER2 growth factor protein -- an important finding given that many scientists had thought that loss of HER2 was likely responsible for Herceptin resistance.
"Herceptin has revolutionized the care of HER2-positive breast cancer for many patients, but unfortunately, not for some. This work demonstrates that digging deeper into the molecular subtypes of these tumors helps us understand why some tumors are resistant and may point to ways to remedy that," said the study's lead author, Lyndsay Harris, M.D., associate professor and Director of the Breast Cancer Disease Unit at Yale University Medical Center.
If additional studies validate these findings, it may be possible to select those patients that will be resistant to Herceptin and treat them with additional drugs to restore Herceptin sensitivity, according to Harris. "Our goal is to see what the tumor tells us before any treatment starts and tailor therapy accordingly," she said.
To determine Herceptin sensitivity, investigators took a small tumor biopsy from 48 patients with newly diagnosed and operable stage II/III breast cancer. They examined the biopsy tissue using both single and multi-gene microarrays, looking for RNA that has been activated to produce proteins.
They then treated the women with a combination of Herceptin and the chemotherapy drug Navelbine weekly for 12 weeks. Although this is not the first study to test Herceptin use before surgery, it is the first to examine the use of Navelbine, a drug approved for lung cancer treatment, in combination with Herceptin to treat HER2-positive tumors. "We were motivated to use Navelbine because we found it has few side effects when used to treat metastatic breast cancer," said Harris, who conducted much of the research study at Harvard before moving to Yale.
After treatment, the tumors were surgically removed and gene chips were again used to examine RNA transcription -- making these investigators the first to use such a technique on Herceptin treated tumors. "This kind of profiling has been done to look at response to chemotherapy drugs, but not at Herceptin resistance," Harris said.
The researchers then divided tumors into groups depending on how well they responded to therapy, and examined the baseline and post-therapy RNA profiles to find genes that were more commonly expressed in Herceptin sensitive and Herceptin resistant tumors.
They first found that some single gene markers, such as HER2 and ER (estrogen receptor), did not change in the majority of tumors. "That tells us that the cancer cells are still creating HER2 surface proteins even as Herceptin is being used, and that means HER2 loss does not appear to be a mechanism of resistance in early stage breast cancer," Harris said.
Then, using multigene chips, the researchers derived a bevy of transcribed genes that likely play a role in Herceptin resistance. Some, such as IGF-1R, were suspected, because this protein is frequently over-expressed in breast tumors, Harris says, but others were not. For example, non-responding tumors were more likely to express genes associated with basal-like breast cancer, which the researchers found to be surprising. "Most basal-like tumors are HER2-negative," Harris said.
Herceptin resistant tumors were also more likely to express a variety of growth factors, suggesting that "activation of parallel pathways may release tumors from dependence on HER2 proliferation and survival," she said.
Although the study was not designed to look at outcome, the researchers determined that 42 of 48 patients had a clinical response (16 complete responses and 26 partial responses) from the neoadjuvant treatment, and five patients experienced cardiotoxicity. After a median 2.6-year-follow-up, three of 48 patients relapsed and one died of her disease.
The study was funded by the National Cancer Institute's SPORE grant to the Dana-Farber/Harvard Cancer Center and the Department of Defense Clinical Translational Research Award granted to Dr. Harris in 2003.
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EVEN TINY BREAST TUMORS CAN BE AGGRESSIVE AND MAY REQUIRE MAXIMUM THERAPY
Monday, December 17, 2007
SAN ANTONIO — Breast tumors that are 1 centimeter in size or smaller — no more than 0.4 inch in length — can still be very aggressive and may require more intensive therapy than is routinely offered today, say researchers at Mayo Clinic in Jacksonville, Fla.
The study, which is being presented at the San Antonio Breast Cancer Symposium, is one of the few that has looked at outcomes of women who have tiny tumors that have not spread to the lymph nodes. The findings suggest that outcome of two types of breast cancer — those classified as HER2 positive (HER2+) and triple negative — may not depend on size alone.
"This is a small study and so we can't make treatment recommendations from it, but it appears that biology and not only size matters when it comes to selecting therapy for small, invasive tumors," says the study's lead researcher, Surabhi Amar, M.D., a fellow in Hematology/Oncology at Mayo Clinic in
Currently, there are no definitive treatment guidelines for tumors less than 1 centimeter in size because clinical trials are usually conducted on women whose tumors are larger or are associated with lymph node involvement, Dr. Amar says. "We just don't have extensive data on tumors this small, so treatment becomes a matter of physician discretion."
Researchers at all three Mayo sites — Jacksonville; Scottsdale, Ariz.; and Rochester, Minn. — participated in the study, which examined 401 women who were treated for breast cancer between 2001 and 2005 at the breast cancer clinics in Jacksonville and Scottsdale.
The vast majority (87 percent, or 350 women) had tumors that were classified as ER/PR positive and HER2 negative (in short, HER2 negative/ER/PR+). Twenty-seven women (6.7 percent) had tumors that were HER2+ and 24 patients (5.9 percent) were diagnosed with triple negative cancer — that is, ER/PR negative and HER2 negative. These classifications refer to receptors present on the outside of the tumor cell that are fueling growth, and cancer that is ER/PR+ is considered the least aggressive of the three categories. Generally, studies have shown that in all patients diagnosed with breast cancer, 15 to 20 percent of breast cancers are HER2+ and about 10 to 15 percent are triple negative.
Patients were followed for an average of almost three years, and so far researchers have data on all patients with HER2+ and triple negative cancers and on 219 women with HER2 negative/ER/PR+ cancer. Researchers found that:
* There were many more grade 2 and grade 3 tumors in women with the two rarer subtypes — 92 percent in HER2+ cancer and 91 percent in triple negative cancer — compared to HER2 negative/ER/PR+ cancer (36 percent). Tumors are graded 1-3, and higher grade tumors are more likely to grow faster and be more difficult to treat than lower grade tumors.
* Cancer came back more frequently in HER2+ tumors (7.4 percent of patients relapsed) and triple negative cancers (12.5 percent), compared to HER2 negative/ER/PR+ cancer (1.3 percent).
* Although the overall outcome of these small, lymph-node-negative tumors was excellent (overall survival 97.4 percent, disease free survival 95.1 percent), these outcomes were different in the three subgroups studied. The death rate was higher in triple negative breast cancer: there was one death in the 24 patients with triple negative tumors, none in the HER2+ group of 27 women, and one death related to relapse in 219 women with HER2 negative/ER/PR+ cancer.
Although only small numbers of women have the rarer cancer subtypes included in this study, the findings suggest that women with HER2+ and triple negative tumors should receive as much treatment as possible in order to prevent cancer relapse, Dr. Amar says. Researchers found that only 35 percent of women with triple negative cancer were treated with adjuvant chemotherapy (chemotherapy after surgery) despite the higher grade of the tumors. "Chemotherapy may not work as well as we would like in these tumors, but, still, physicians who treat patients with triple negative cancer should be aware of the higher risk of relapse, even if tumors are quite small," she says.
Adjuvant chemotherapy was offered to 28 percent of patients with HER2+ tumors, and only 4 percent received the targeted therapy Herceptin, which has been designed specifically to treat this class of tumors. "Should Herceptin be offered to such small node-negative tumors? There is not enough data currently to answer this question," Dr. Amar says. "But this study definitely highlights the fact that HER2 positive tumors, even if very small, may warrant more aggressive therapy."
Only 3.9 percent of patients with HER2 neg/ER/PR+ cancer were treated with chemotherapy. "So although the rates of adjuvant chemotherapy use were significantly higher in the HER2+ and triple negative subgroups, these groups still showed a higher relapse rate," she says.
The study's senior investigator is Edith A. Perez, M.D., director of Mayo Clinic's Multidisciplinary Breast Clinic in
http://www.mayoclinic.org/news2007-jax/4385.html
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MAYO CLINIC-LED STUDY IMPROVES BREAST CANCER RISK PREDICTION IN WOMEN WITH ATYPIA
Women with at least three sites of cellular atypia in breast tissue are nearly eight times more likely than average women to develop breast cancer, according to findings of a
Several previous studies have shown that atypical hyperplasia (also called atypia) in breast tissue is a major risk factor for breast cancer. Women who have a breast biopsy and are diagnosed with atypia are considered at high risk. Many are counseled to consider preventive medications such as tamoxifen or other risk-reducing approaches. However, questions remained from prior research on whether a positive family history further increases risk in women with atypia and for how long the increased risk in women with atypia lasts.
"The most commonly used tool for risk prediction in women with atypia is the Gail model, which may predict inaccurately because our study shows that family history does not change risk significantly in women with atypia," says Amy Degnim, M.D., a Mayo Clinic surgeon and study author. "Our findings indicate that women with atypia have a higher absolute risk for breast cancer than previously estimated. This risk is 25 percent over 25 years and is much higher in women with multiple areas of atypia and calcification." The Gail model predicts risk by using age at onset of menses, age at birth of first child, number of previous breast biopsies, presence of atypia, and number of close relatives with breast cancer.
While the Mayo Clinic study found that family history did not further increase risk, age at diagnosis of atypia did affect risk, with younger women (under age 45) more than twice as likely to develop breast cancer compared to women diagnosed with atypia after 55. The number of areas of atypical hyperplasia was significant as well. With one area of atypia, breast cancer risk was 2.3-fold compared to the general population; this risk more than doubled when two sites were found and increased to nearly eightfold as sites increased to three or more. The group of women with the highest risk had three or more areas of atypia and calcification — with a 10.4-fold risk over the general population.
"With the ability to stratify the risk of breast cancer in women with atypia, we can have more informed discussions with our patients regarding their personal risk," says Dr. Degnim. "This will help us to have individualized discussions regarding how aggressively to pursue risk-reduction treatments."
These findings resulted from reviewing the records of 331 women with atypia identified within the Mayo cohort of 9,376 women who had benign breast biopsies surgically obtained between 1967 and 1991. More than half (55.9 percent) of the women were over age 55 when diagnosed with atypia, and 42.9 percent had a family history of breast cancer. The majority (68.6 percent) of women showed calcification in the biopsy tissue, and 40 percent had multiple sites of atypical hyperplasia.
The American Cancer Society reports that more than 240,000 women will be diagnosed in the
Other Mayo researchers included senior author Lynn Hartmann, M.D.; Marlene Frost, Ph.D.; Robert Vierkant; Shaun Maloney; V. Shane Pankratz, Ph.D.; Piet de Groen, M.D.; Wilma Lingle, Ph.D.; Karthik Ghosh, M.D.; Lois Penheiter; L. Joseph Melton III, M.D.; and Carol Reynolds, M.D. Collaborators from other institutions included Daniel Visscher, M.D., University of Michigan; Hal Berman, M.D. and Thea Tlsty, Ph.D., University of California, San Francisco; and Thomas Sellers, M.D., Ph.D., H. Lee Moffitt Cancer and Research Institute, Tampa, Fla.
The research was supported in part by a Department of Defense Center of Excellence Grant, the Susan G. Komen Breast Cancer Foundation, the Breast Cancer Research Foundation, and the Fred C. and Katherine B. Andersen Foundation. For more information about breast cancer and other research at
To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. MayoClinic.com is available as a resource for your health stories.
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NORMAL TISSUE NOT SPARED IN NEW FORMS OF BREAST CANCER RADIOTHERAPY
Tuesday, October 30, 2007
That because the short treatment, known as partial breast irradiation, focus radiation to a small sector of the breast through multiple beams, these beams can pass through the breast to the heart and lungs that lie behind, researchers found. Radiating the entire breast over weeks, as is standard practice, can expose much of the heart and lungs to long periods of lower dose radiation, they say.
These findings, presented at the annual meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO), suggest that both methods carry risks and benefits that may be equivalent, says the study's lead investigator, Laura Vallow, M.D.
"This tells us that the standard course of therapy isn't that bad in terms of its exposure to normal tissue, but also that, sometimes, partial breast irradiation may not spare as much normal tissue as we hope," Vallow says.
Oncologists are currently testing the two modes of radiotherapy - whole breast irradiation (WBI) and 3-D conformal partial breast irradiation (PBI) - in a large federally-supported clinical trial that is enrolling thousands of women across the country who have been diagnosed with early stage breast cancer and have undergone lumpectomy.
The hope is that a short course of radiotherapy will be as effective as the much longer course, and that this could lead to increased use of breast conservation over mastectomy, Vallow says. "Many women may be opting for a mastectomy instead of a lumpectomy in order to avoid weeks and weeks of radiation treatment," she says. "If the results of both methods are equivalent, then perhaps some of these women will choose less drastic surgery."
In two studies being presented at ASTRO, Vallow, along with Ashley Gale, M.S., Anudh Jain, M.D., and a team of physicists at Mayo Clinic Jacksonville, used radiological parameters that were prepared for patients in the clinical trial and employed computers to assess how much of normal heart and lung tissue would be exposed if either WBI or PBI were used.
"We suspect there are fundamental differences in the amount of exposure to radiation a patient has using these techniques, but no one has ever looked at how much normal tissue is spared," she says. "We are interested in the finer points of treatment planning, with the ultimate goal of making treatment more tolerable with less radiation exposure."
In the first study, the researchers analyzed radiation plans for 25 patients enrolled in the clinical trial and they calculated what radiation to the lung would be if WBI or PBI was used. They found that PBI exposes a slightly larger volume of the lung to low doses of radiation, but also exposes a smaller volume of lung to high doses than WBI does.
"Patients are getting more exposure overall to their lungs with partial breast irradiation but less lung tissue is irradiated to higher doses compared to whole breast irradiation," Vallow says.
For 14 of the same patients who had a lumpectomy in their left breast, investigators calculated radiation to normal heart tissue. They found that PBI and WBI delivered about the same amount of radiation to the heart of patients whose tumor was located in the middle of the breast. In patients whose tumors were closer to the armpit, PBI did not affect normal heart tissue, Vallow says.
"This study shows how far we have really come in the delivery of radiotherapy," she says. "We are looking for nuances of tissue exposure."
To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. MayoClinic.com is available as a resource for your health stories.
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DRUG COMBINATION SHRINKS BREAST CANCER
METASTASES IN BRAIN
ScienceDaily (Dec. 17, 2007) — A combination of a "targeted" therapy and chemotherapy shrank metastatic brain tumors by at least 50 percent in one-fifth of patients with aggressive HER2-positive breast cancer, according to data presented by Dana-Farber Cancer Institute investigators at the San Antonio Breast Cancer Symposium.
Lapatinib (Tykerb) and capecitabine (Xeloda) were paired in an extension of a Phase 2 clinical trial in which lapatinib given alone shrank brain metastases significantly in six percent of 241 patients.
In the extension trial, capecitabine was added to lapatinib in 49 patients whose metastases -- cancerous colonies in the brain spread from their primary cancer -- had progressed while on treatment. With the combination therapy, brain metastases shrank by 20 percent or more in 18 patients (37 percent) and shrank by at least 50 percent in 10 patients (20 percent), reported Nancy Lin, MD, of Dana-Farber's
"Very few medications have shown activity in the treatment of brain metastases, particularly in HER-2-positive metastatic breast cancer patients," said Lin, who led the study with Eric Winer, MD, director of the
Lapatinib is an oral small-molecule drug from GlaxoSmithKline that is approved along with capecitabine for treating patients with advanced or metastatic breast cancer whose tumors are driven by the abnormal growth signal, HER-2, and who have already undergone therapy including trastuzumab (Herceptin), a taxane drug, and an anthracycline compound. Lapatinib, like trastuzumab, blocks the HER-2 signal.
Up to one-third of women with advanced, HER-2-positive breast cancer may develop metastases to the brain.
"Although radiation treatment is often effective, as women live longer with metastatic cancer, some develop worsening of brain metastases despite radiation," said Lin. "Because cancer in the brain can have a major impact on quality of life, it is important to have treatment options to address this problem."
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BREAST CANCER RISK IN SMOKERS
Common gene boosts breast cancer risk in smokers
The gene involved, N-acetyltransferase 2 (NAT2), is believed to help clear the body of aromatic amines, a major carcinogen in tobacco smoke. The researchers found that women with the slower-acting form of this gene -- who represent 50 percent to 60 percent of the white population and 35 percent to 40 percent of African-Americans -- are more likely to get breast cancer if they smoke.
But the study's lead author said the finding shouldn't motivate people to undergo; instead, she said, it should spur them to quit smoking. "We still know very little about what these genes do and how they might affect risk-we think the most important thing for people to do is to live a healthy lifestyle," Dr. Christine B. Ambrosone of the Roswell Park Cancer Institute in
It has been known for years, Ambrosone noted, that the risk of bladder cancer is higher in people with the slow-acting gene version, known as the slow acetylator NAT2 genotype. However, research to date has not found any link between cigarette smoking and overall breast cancer risk. Scientists had theorized that smoking might actually reduce breast cancer risk because it can lower estrogen levels.
To investigate whether the presence of genetic mutations may influence the smoking-breast cancer relationship, Ambrosone and her colleagues analyzed data from 13 studies including a total of 11,922 women.
For women with the slow-acting gene, the researchers found, breast cancer risk increased with the number of pack years smoked, but smoking had no effect on breast cancer risk in women with the fast-acting genotype.
However, women with the slow-acting gene who smoked for at least 20 pack years -- the equivalent of a pack a day for 20 years --were 44 percent more likely to develop breast cancer than non-smokers. Theis iIncreased risk was seen for both premenopausal and postmenopausal women with the slow acetylator NAT2 gene.
"Because of the frequency of slow acetylator genotypes among non-Asian populations...smoking cessation programs need to be further targeted to women as a means for preventing breast cancer," Ambrosone and her colleagues conclude.
"What we believe is important is the public health message," the researcher said. "Here's one more adverse health outcome that smoking is likely related to."
SOURCE: Cancer Epidemiology, Biomarkers and Prevention, January 2008.
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Drug Found Effective In Treating, Preventing Breast Cancer
ScienceDaily (Nov. 1, 2007) — A new study of an estrogen-derived drug shows promise as a treatment for breast cancer and breast cancer metastases to bone. A drug that has shown promise in treating sarcoma, lung and brain cancers, demonstrates that the drug may also be effective in treating breast cancer, in particular the spread of breast cancer.
The study, which was done in mice, appears on the cover of the November issue of Cancer Research.
Urszula Iwaniec, an assistant professor in the Department of Nutrition and Exercise Sciences at OSU, is the one of the authors of the study, along with OSU professor Russell Turner and researchers from the Mayo Clinic. Iwaniec and Turner are both researchers at OSU's Skeletal Biology Laboratory.
In breast cancer, the cancer commonly lodges in the bone, destroying it in a debilitating painful process called osteolysis. Osteolysis can lead to bone fractures and causes patients to feel tired, or even to lose consciousness.
Iwaniec and Turner studied the effect of 2-methoxyestradiol (meth-oxy-es-tra-di-ol), or 2ME2, on the bone. 2ME2 is derived from estrogen and works by suppressing tumor growth and blocking the formation of new blood vessels that feed tumors.
"We were expecting the drug to have an effect, but we were not expecting to have as big of an effect as it did," Iwaniec said.
In studies of other cancers, 2ME2 has been shown to induce cancer cells to self-destruct. Otherwise, tumor cells evade this process allowing them to continually divide and spread throughout the body.
Clinical trials of 2ME2 for breast cancer patients are in progress. These trials are based on an oral version of 2ME2 to treat primary tumors, but this method has limitations as the oral version of 2ME2 is poorly suited to getting into the blood system and reaching tumors. Researchers resolved this problem by delivering 2ME2 by injection and found it was much more effective.
Researchers described 2ME2 as an "attractive candidate for controlling tumor growth, metastasis to bone and bone disorders," such as osteolysis caused by the spread of breast cancer.
"This is potentially of very substantial importance because this agent has few of the unpleasant side effects of most chemotherapy drugs and targets both bone resorption and the cancerous tumor cells," Turner said. "It really is the first agent that has been clearly demonstrated to do that."
Turner said current drugs that are used to prevent bone fractures and bone pain in cancer patients are not effective in targeting the tumor cells. Turner has spent the past decade studying 2ME2 as a treatment for osteoporosis and a rare bone cancer called osteosarcoma, and is excited about its prospects as a cancer treatment.
"Often, treatments that are good for cancer are bad for the bones," he said. "2ME2 appears to be capable of treating both. If you had a treatment that both reduced the risk of bone cancer and osteoporosis, it would be extremely significant."
In summary, the researchers found that 2ME2 could:
* Effectively target breast cancer cells;
* Prevent the spread of breast cancer cells to bone;
* Protect bone from osteolysis, which is a type of bone metastasis in which the bone is eaten away by cancer cells.
The next step for the Mayo Clinic and OSU researchers is to replicate and test the finding in clinical trials.
The study was funded by a grant from the National Institutes of Health and the Mayo Clinic.
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