Hormone test predicts ovarian function after chemotherapy for breast cancer

ScienceDaily (June 5, 2011) — A test that shows how many eggs a woman has in her ovaries may help young women with breast cancer know what their reproductive function will be after chemotherapy, a new study finds.

See Also:Health & MedicineWomen's HealthBreast CancerLung CancerMenopauseOvarian CancerColon CancerReferenceMenopauseHysterectomyOvarian cancerInfertility

The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.

Called the anti-Mullerian hormone (AMH) test, this blood test measures levels of an ovarian hormone that reflects the size of the ovarian reserve, or remaining egg supply. Currently, doctors use it to quantify a woman's ovarian reserve before in vitro fertilization treatments. Now researchers from Scotland have found that measurement of AMH indicates how likely it will be for a woman to still have eggs in her ovaries after chemotherapy, which can often damage a woman's eggs and cause infertility.

"Future reproductive function is a concern for many young women with cancer," said lead investigator Richard Anderson, MD, PhD, professor of clinical reproductive science at the University of Edinburgh. "This test will be of benefit to women with newly diagnosed cancer to help decide whether they need to take steps to preserve their fertility."

In the U.S. alone, breast cancer is diagnosed in more than 25,000 women younger than 45 each year, according to the American Cancer Society.

For this study, Anderson and his colleagues recruited 50 premenopausal women, ages 29 to 51, who had just received a diagnosis of early breast cancer. All women had normal menstrual cycles and were asked to keep a daily record of their menstrual cycle, as an index of ovarian activity, during the two years of the study. Before the women started chemotherapy, they gave blood samples for AMH testing. They again had AMH tests one and two years after starting treatment.

Before chemotherapy the median AMH level was 0.4 nanograms per milliliter (ng/mL). After cancer treatment the AMH level fell rapidly, becoming undetectable (below 0.16 ng/mL) in 68 percent of the women after one cycle of chemotherapy, the authors reported. By one-year follow-up, 11 women withdrew from the study, mostly because of cancer recurrence, Anderson said. Menstrual records were available for 39 women at one year and for 29 women at two years.

A low AMH measurement before treatment correlated well with amenorrhea, or absence of menstruation, after treatment. Women whose AMH before treatment was low (below 0.4 ng/mL) were 16 times likelier to have stopped menstruating after chemotherapy than women with a high pretreatment AMH value, Anderson said. The odds of losing ovarian function remained higher even after statistical analysis controlled for increasing age, which tends to lower AMH levels. Women whose AMH before chemotherapy exceeded 0.92 ng/mL were reportedly almost five times more likely to continue menstruating after treatment.

"Our data suggest that the AMH test, taken before cancer treatment, can help individualize a woman's infertility risk after chemotherapy for breast cancer," Anderson said.

He added that results of this study, which was funded by the U.K. Medical Research Council, are likely to apply to other types of cancer as well.

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Novel imaging agent targets breast tumor development

ScienceDaily (June 6, 2011) — Scientists presented new research at SNM's 58th Annual Meeting that has the potential to help physicians detect breast cancer by imaging the proliferation of blood vessels carrying oxygen and nutrients to breast tumors. Their study is evaluating a new imaging agent that is naturally drawn to angiogenesis -- the development of new blood vessels in tissues both normal and cancerous. This process turns malignant during the growth stage of many cancerous tumors including those in breast tissue.

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"The positive outcomes of this study are encouraging and may provide clinicians with additional information for breast cancer management," says Andrei Iagaru, MD, lead author of the study and assistant professor of radiology and nuclear medicine at Stanford University Medical Center, Stanford, Calif. "PET imaging with this agent could potentially lead to better clinical decisions; patients with progressive cancer who are ideal candidates for aggressive therapies could be identified earlier to improve their prognosis."

The new imaging agent central to this study is called 18F FPPRGD2, which combines the medical isotope fluorine-18 (18F) with a protein biomarker ideal for imaging the expression of an integrin known as αvβ3. Integrins are essentially protein-based receptors that regulate the adhesion between cells and connecting tissues. They are also involved in cell signaling, which mediates a cell's shape, movement and lifecycle, but their most useful trait is their key involvement in angiogenesis. Upon injection the agent seeks out tissues in a state of angiogenesis and is then captured using a molecular imaging technique known as positron emission tomography (PET), which produces functional imaging of the body.

Six female participants with breast cancer were recruited for the study and were imaged twice using 18F FPPRGD2 and 18F FDG PET/CT within two weeks. PET imaging with 18F FPPRGD2 showed superior functionality for identifying angiogenesis in breast tissue, with strong uptake and distribution in both primary cancers and metastatic lesions.

Further studies evaluating the effectiveness of 18F FPPRGD2 for targeting breast tumor angiogenesis could lead to its availability for clinical use for patients known to have breast cancer. This agent could be an effective tool for cancer staging and may improve patient treatment planning as a result of the information it provides. Preliminary findings show that it could become a useful weapon in the fight against breast cancer.

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Breast cancer research: Mammary gland development of blueberry-fed lab animals studied

ScienceDaily (June 7, 2011) — U.S. Department of Agriculture (USDA)-funded studies of mammary gland development in laboratory rats fed blueberries or other foods of interest may aid breast cancer research.

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In an early study that has paved the way to follow-up experiments, Rosalia C. M. Simmen of the Arkansas Children's Nutrition Center (ACNC) in Little Rock, Ark., has determined that several indicators of rat mammary gland health were improved in the offspring (pups) of mothers (dams) that had been fed 5 percent blueberry powder in their rations during pregnancy and during the weeks that they nursed their pups.

The powder comprised 5 percent of the total weight of the feed, according to Simmen, a senior investigator at the center and a professor at the University of Arkansas for Medical Sciences in Little Rock.

The ACNC is a partnership between the USDA's Agricultural Research Service (ARS), Arkansas Children's Hospital in Little Rock, and the university.

The effects noted in the blueberry study have not been shown in humans and have not yet been traced to a particular blueberry compound, Simmen noted.

Her team evaluated several structural indicators of normal mammary gland development in the lab animals, including branching of the gland. There was significantly more branching in the offspring of the group that consumed the diet containing 5 percent blueberry powder than in offspring of dams fed rations containing 2.5 percent or 10 percent blueberry powder, Simmen reported.

Branching occurs when cells specialize or differentiate. Differentiation is generally preferable to rapid proliferation of undifferentiated cells, which can be a risk factor for breast cancer.

In their analysis of several biochemical indicators, the team found, for instance, that the level of the tumor-suppressing protein PTEN (phosphatase and tensin homolog deleted in chromosome 10) was significantly higher in mammary tissues of offspring of dams on the 5 percent regimen. That's a plus, because PTEN is thought to help protect against cancer.

Lab animal studies of blueberries' potential role in preventing breast cancer date to 2006. But Simmen's investigation, published in Nutrition Research in 2009, provided the first evidence from a lab animal study of the early influence that the mother's blueberry consumption can have on normal, healthy development of the mammary gland in her offspring.

Simmen collaborated in the research with ACNC colleague Xianli Wu; former ACNC research chemist Ronald L. Prior, now retired; and Ph.D. student Omar Rahal.

Read more about these experiments in the May/June 2011 issue of Agricultural Research magazine at: http://www.ars.usda.gov/is/AR/2011/may11/fruit0511.htm

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Crucial molecule involved in spread of breast cancer identified; Findings suggest strategy for halting metastasis

ScienceDaily (June 8, 2011) — Researchers at Albert Einstein College of Medicine of Yeshiva University have identified a key player in the spread of breast cancer. The findings, published in the online edition of Nature, identify a critical molecule that helps cancer spread beyond the primary tumor. The research highlights a potential new strategy against metastatic disease. The study's senior author is Jeffrey Pollard, Ph.D., professor of developmental and molecular biology and of obstetrics & gynecology and women's health at Einstein. He also holds the Louis Goldstein Swan Chair in Women's Cancer Research and is the deputy director of the Albert Einstein Cancer Center.

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People rarely die from their primary (original) tumor. Instead, most cancer deaths occur because the cancer has spread, or metastasized, to other parts of the body. "By focusing on sites where cancer had spread, we were able to detect a molecule that stimulates metastasis," said Dr. Pollard. "This raises the possibility that metastasis could be kept from progressing -- or even prevented -- if the stimulating molecule could be blocked. This we achieved in mouse models of breast cancer."

Metastasis begins when cells break away from the primary tumor and gain the ability to move on their own. These cells invade nearby blood vessels (a process known as intravasation) and are carried by the bloodstream to other parts of the body. The bloodborne tumor cells then escape from vessels in a process known as extravasation. Once these tumor cells escape from the vessels, they seed new and deadly tumors that grow in these distant locations.

In previous studies, Dr. Pollard and his research team have shown that macrophages -- immune system cells whose functions include fighting infections -- actually promote the spread of cancer. His research has shown that macrophages not only assist tumor cells during both intravasation and extravasation but also help those wayward cells take root in their new locations and grow into metastatic tumors. In the current study, Dr. Pollard and colleagues investigated the process by which these macrophages are recruited to metastatic sites and subsequently promote tumor-cell extravasation, seeding and tumor growth.

Using models of human and mouse breast cancer, the researchers demonstrated that when breast tumor cells travel to the lung, these cells secrete CCL2, a chemokine molecule (i.e., one that attracts cells). CCL2 attracts immune cells called inflammatory monocytes -- in particular, those bearing receptors for CCL2, which then develop into macrophages. The monocytes and macrophages "invited" by CCL2 signaling then facilitate extravasation -- the critical step in metastasis in which bloodborne tumor cells cross the vessel wall and implant in nearby tissue. One way monocytes help tumor cells escape from blood vessels and cause metastasis, the Einstein researchers found, is by secreting vascular endothelial growth factor, or VEGF, a substance that makes blood vessels leaky at the site where tumor cells exit from them.

Once the tumor cells are seeded, inflammatory monocytes continue to flock to the metastatic site -- now attracted by CCL2 secreted not only by the tumor cells but also by nearby lung tissue that the tumor cells have targeted. In turn, these continuously recruited monocytes and the resultant macrophages promote the growth of the emerging metastatic tumor.

To confirm their findings, the researchers used anti-CCL2 antibodies to suppress CCL2 signaling in a mouse model of human metastasis -- with striking results. In lungs challenged with metastatic tumor cells, the anti-CCL2 antibodies inhibited the influx of inflammatory monocotyes and macrophages to the metastatic sites, and the number of metastatic sites that developed in the lungs was markedly reduced. In addition, the mice lived much longer when CCL2 signaling was blocked.

"These findings have potential implications for therapy, since in human breast cancer we know that CCL2 expression and macrophage infiltration are associated with poor prognosis and metastatic disease," said Dr. Pollard. "If we can develop ways to inhibit these processes, we might be able to slow or stop breast cancer from spreading."

Dr. Pollard's coauthors include Bin-Zhi Qian, Ph.D.; Jiufeng Li; Hui Zhang; Takanori Kitamura, Ph.D.; and Jinghang Zhang, M.D., of Einstein and Liam R. Campion, M.S.; Elizabeth A. Kaiser; and Linda A. Snyder, Ph.D., of Ortho Biotech Oncology R&D, Radnor, PA. The research was funded by grants from the National Cancer Institute of the National Institutes of Health.

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Breast cancer drug pushes colon cancer cells to their death

ScienceDaily (June 9, 2011) — A new treatment for colon cancer that combines a chemotherapy agent approved to treat breast cancer and a cancer-fighting antibody is ready for clinical trials, according to Penn State College of Medicine researchers.

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More than 150,000 cases of colorectal cancer are diagnosed each year, and about 50,000 people die from colorectal cancer yearly. Currently there are limited chemotherapy treatments for colorectal cancer with little that has been in the pipeline in recent years.

Wafik S. El-Deiry, M.D. Ph.D., American Cancer Society Research Professor and Rose Dunlap Professor and chief of hematology/oncology, and his team have tested lapatinib, a targeted chemotherapy agent currently approved for breast cancer treatment, in a new combination with artificial antibodies that mimic a natural cancer-fighting protein produced in the human body. The monoclonal antibodies mapatumumab and lexatumumab act similarly to TRAIL -- tumor necrosis factor

Signaling pathways point to vulnerability in breast cancer stem cells

ScienceDaily (June 11, 2011) — Whitehead Institute researchers have identified signals from breast epithelial cells that can induce those cells to transition to and maintain a mesenchymal and stem cell-like cell state that imbues both normal and cancer cells with a greater ability to migrate and self-renew. Interrupting these signals strips the cells of the migratory, invasive and self-renewal abilities used by cancer stem cells to seed new tumors.

See Also:Health & MedicineStem CellsCancerBreast CancerSkin CancerProstate CancerBrain TumorReferenceEmbryonic stem cellTumorSomatic cellHealing

"Stem cells are important in both cancers and normal tissues. On the one hand we'd like to know what creates so-called cancer stem cells in tumors and on the other hand we'd like to know what creates normal stem cells in normal epithelial tissues," says Whitehead Founding Member Robert Weinberg. "We have reason to believe that these two dynamics are orchestrated by a common regulatory machinery. So this work may be applicable for understanding both breast cancer cells and normal epithelial cells, such as the normal cells in the normal mammary ducts."

During an epithelial-to-mesenchymal transition (EMT), epithelial cells acquire the traits of mesenchymal cells. Unlike the tightly-packed epithelial cells that stick to one another, mesenchymal cells are loose and free to move around a tissue. The attributes of mesenchymal cells are beneficial during development, but when hijacked by cancer cells, confer the ability to migrate to distant sites. In addition, the passage through an EMT enables adult cancer cells to seed new tumors with high efficiency, the hallmark trait of cancer stem cells. Although passage through an EMT is recognized as an important step in the formation of cancer stem cells, scientists have been unable to clearly identify the cues in a cell's microenvironment that induce an EMT.

By studying human breast epithelial cells, Christina Scheel, a postdoctoral researcher in the Weinberg lab, pinpointed three signaling pathways (TGF-beta, non-canonical Wnts, and canonical Wnts) that work together to maintain migratory and self-renewing traits of both normal breast epithelial and breast cancer cells. These pathways are continuously activated in the stem cells by autocrine signals; that is, signals produced by the cells themselves. Studying how these autocrine signals function in breast epithelial cells allowed Scheel to specify the signals that allow these cells to pass through an EMT and enter into a mesenchymal and stem cell-like state in the first place. Her findings are published in the June 10 issue of Cell.

Interestingly, Scheel discovered that epithelial cells are kept in their differentiation state via inhibition of the three signaling pathways, that is, normal epithelial cells naturally produce proteins that block these signaling proteins. To push normal breast epithelial cells through an EMT in vitro, she removed these endogenous inhibitors by administering a cocktail of neutralizing antibodies and added growth factors that stimulate the three pathways, thereby mimicking the autocrine signaling found in mesenchymal cells. By applying the resulting EMT-inducing cocktail continuously, Scheel pushed the cells into a mesenchymal and stem cell-like state, with associated increased migratory ability and stem cell-like characteristics. Eventually, the former epithelial cells stabilized this state through autocrine signaling and were no longer dependent on the EMT cocktail.

To see the effects of blocking this autocrine signaling in an animal model, Scheel implanted into mice human breast cancer epithelial cells that had passed through an EMT. She then injected the implantation site with proteins that block the three pathways. The injected mice had one-tenth the number of tumors found in mice that did not receive the inhibitory proteins. In addition, breast cancer cells that were pre-treated in vitro with these proteins displayed a greatly reduced ability to metastasize when subsequently implanted into mice.

Scheel notes that these experiments show how cancer cells' knack for usurping normal cell functions could ultimately lead to their downfall.

"These autocrine signals are not something breast cancer cells invent anew, but derive instead an activation of normal stem cell programs," says Scheel. "Breast cancer stem cells rely on these signals to maintain themselves, so they remain susceptible to blocking this autocrine signaling. It might be a terrific way to target breast cancer stem cells. In addition, our gain in understanding how both migratory and self-renewal traits are activated in normal breast epithelial cells might further our understanding of normal tissue homeostasis and might be of great utility in the area of regenerative medicine, where it would be highly desirable to create great numbers of epithelial stem cells without resorting to genetic intervention."

Although Scheel's research gives new insight into how both cancer and normal breast cells transition to and maintain a mesenchymal cell state, she and Weinberg caution that the same signals and signaling pathways may not apply for non-breast cells.

"Are the same agents signaling the EMT in non-mammary tissues -- the skin, liver, the gut, pancreas and so forth? We don't know the generalizability of Scheel's findings yet, although I can imagine that there are many commonalities," says Weinberg, who is also a professor of biology at MIT and the Director of the MIT/Ludwig Center for Molecular Oncology. "Secondly, we don't know if these three signaling pathways are ultimately those that are critically important for activating the EMT in non-mammary cell types. Alternatively, there may be other contextual signals besides these three that play an equally important role in triggering an EMT in non-mammary cells? Whether these signaling pathways turn out to have a degree of universality, we just don't know."

This research was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI), Massachusetts Institute of Technology Ludwig Center for Molecular Oncology, Ludwig Fellowship for Metastasis Research, Breast Cancer Research Foundation, Harvard Breast Cancer Specialized Program of Research Excellence (SPORE), Department of Defense Breast Cancer Research Program Idea Award, and Samuel Waxman Foundation.

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Silencing a deadly conversation in breast cancer

ScienceDaily (June 2, 2011) — While it is already known that breast cancer cells create the conditions for their own survival by communicating their needs to the healthy cells that surround them, Australian researchers have identified a new way of turning off that cellular cross talk.

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They have shown that a molecule known as 'hedgehog' sits at the centre of the switchboard in breast cancer, transmitting biochemical signals between the cancer cells and healthy cells.

When this conversation is blocked -- or hedgehog is 'silenced' -- tumours shrink and stop their spread.

While the finding applies to all breast cancers, it is particularly relevant for women with basal breast cancer, for which there is no current targeted therapy.

The good news is that drugs for silencing hedgehog are already undergoing Phase 2 clinical trials in other cancer types.

Clinical Associate Professor Sandra O'Toole and Dr Alex Swarbrick, from Sydney's Garvan Institute of Medical Research, analysed breast tumour samples from a cohort of 279 women with advanced breast cancer, revealing that the higher the level of hedgehog, the more aggressive the cancer.

Having discovered high levels of hedgehog in some breast cancer patients, they went on to over-produce the protein in mouse models of basal breast cancer. Mice developed tumours that grew and spread through the body rapidly. When hedgehog was blocked, the tumour growth and spread were significantly slowed.

These findings are published in the journal Cancer Research, now online.

"We are hopeful that our findings will drive the progress of clinical trials for anti-hedgehog drugs in breast cancer," said Dr Alex Swarbrick.

"Finding an effective drug target for basal breast cancer is a very high priority. It is often referred to as 'triple negative disease', because it doesn't produce any of the oestrogen, progesterone or HER2 receptors, targets of the drugs tamoxifen and Herceptin, which are very effective in other breast cancers."

A/Prof O'Toole, also a pathologist at Sydney's Royal Prince Alfred Hospital, undertook the study as part of her PhD. "These findings may provide some hope to the many women who succumb to breast cancer each year, especially the basal sub-type, although obviously it is early days," she said.

"More work in animal models is needed to understand exactly how best to block this pathway."

"Our study demonstrates that starving breast cancer cells of hedgehog significantly slows their growth and spread."

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New clinical trial to test novel approach to treat triple-negative breast cancer

ScienceDaily (June 2, 2011) — A multicenter clinical trial led by a researcher at the University of Maryland Marlene and Stewart Greenebaum Cancer Center will evaluate a new approach to treat triple-negative breast cancer, an often-aggressive type of cancer that is more common among African-Americans and young women. The study will help researchers determine if an experimental drug, entinostat, can reprogram tumor cells to express a protein called an estrogen receptor to make them sensitive to hormone therapy.

See Also:Health & MedicineBreast CancerCancerLung CancerColon CancerProstate CancerBrain TumorReferenceMetastasisBreast cancerTumor suppressor geneHormone replacement therapy

Saranya Chumsri, M.D., an oncologist at the Greenebaum Cancer Center and assistant professor of medicine at the University of Maryland School of Medicine, is the principal investigator of the newly opened National Cancer Institute-funded study. The trial is based on laboratory studies by Angela H. Brodie, Ph.D., an internationally recognized University of Maryland breast cancer researcher, and her colleagues. Their research, recently published in the journal Cancer Research, found that entinostat can cause triple-negative breast cancer cells to become sensitive to a hormone therapy such as an aromatase inhibitor. Dr. Brodie pioneered the development of aromatase inhibitors, a class of breast cancer drugs that reduces the level of estrogen produced by the body, thereby cutting off the fuel to cancer cells.

In this Phase II trial, doctors will treat newly diagnosed postmenopausal patients with entinostat and an aromatase inhibitor called anastrozole (Arimidex) before they have surgery to remove their cancer. Researchers will analyze tissue from the tumor and blood samples to evaluate whether the treatment is effective. After surgery, patients will receive standard treatment, such as chemotherapy and radiation.

"We hope that entinostat will make the tumor cells more sensitive to the drug anastrozole, causing the tumor to shrink or, at the very least, stop growing," Dr. Chumsri says. "For patients with triple-negative breast cancer, chemotherapy is currently the only drug treatment option, and it has a lot of side effects compared to hormone therapies like anastrozole."

Triple-negative breast cancer is unique in that it lacks three common receptors in the cell -- estrogen, progesterone or human epidermal growth factor 2 (HER2), which are the targets of drugs widely used today to treat breast cancer. As a result, this cancer can be very difficult to treat; it doesn't respond to therapies that target estrogen and progesterone receptors, such as tamoxifen (Nolvadex), fulvestrant (Faslodex) and aromatase inhibitors (Femara, Arimidex and Aromasin), or to HER2-targeted therapies such as trastuzumab (Herceptin) and lapatinib (Tykerb).

About 15 to 20 percent of breast cancers are triple-negative. For unknown reasons, there is a higher prevalence of this type of breast cancer among African-Americans, young women and women with the BRCA1 gene mutation. African-American women are twice as likely as white women to have this type of cancer, which can be very aggressive and spread to other parts of the body, such as the lungs, liver and brain.

The clinical trial is based on laboratory studies by Dr. Brodie, a professor of pharmacology and experimental therapeutics, and Gauri J. Sabnis, Ph.D., an assistant professor of pharmacology and experimental therapeutics, at the University of Maryland School of Medicine, in collaboration with Saraswati Sukumar, M.S., Ph.D., a professor of oncology and pathology at the Johns Hopkins University School of Medicine. Their research showed that entinostat can sensitize triple-negative breast cancer cells to treatment with an aromatase inhibitor, and when combined with an aromatase inhibitor, also reduce the growth and spread of tumors in animal models.

"Adding to her long list of remarkable achievements, Dr. Brodie has continued her research into aromatase inhibitors, searching for ways to overcome tumors' resistance to treatment," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president of medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine. "This multicenter clinical trial led by Dr. Saranya Chumsri is an excellent example of how our scientists turn discoveries made in the lab into new treatments that may benefit patients."

Entinostat is an oral, selective histone deacetylase (HDAC) inhibitor. This anti-cancer agent is being developed by Syndax Pharmaceuticals, Inc., and is being investigated in other clinical studies for the treatment of advanced estrogen receptor-positive breast cancer, advanced non-small-cell lung cancer, advanced colorectal cancer and Hodgkin's lymphoma.

Triple-negative breast cancer patients in this clinical trial will take entinostat weekly and anastrozole once daily for two to four weeks while they are waiting to have surgery. Researchers will use blood tests and tissue analysis of tumors to evaluate the effectiveness of the combination therapy.

Researchers hope to enroll a total of 41 patients at 20 sites, including the University of Maryland Greenebaum Cancer Center. The centers involved in the study are affiliated with the University of Chicago Phase II study research consortium and the California Cancer Consortium.

Dr. Chumsri says that if the results of this trial are positive, researchers plan to launch a larger study to test the combination therapy on women whose cancer has metastasized to other parts of the body. "These women have limited treatment options. Hopefully, this treatment would give them a longer period in which their cancer is not progressing, with only minimal side effects compared to chemotherapy," she says.

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Emerging trends in radiation therapy for women over 70 with early stage breast cancer

ScienceDaily (June 2, 2011) — Patterns of radiation usage in breast conserving therapy for women 70 years and older with stage I breast cancer are changing: more women are opting for radioactive implants and those with estrogen positive tumors are opting out of radiation therapy, according to an abstract being presented at the American Society of Clinical Oncology annual meeting in Chicago by Thomas Jefferson University Hospital researchers.

See Also:Health & MedicineBreast CancerWomen's HealthCancerGynecologyMenopauseGene TherapyReferenceHormone replacement therapyBreast cancerHysterectomyMenopause

In another abstract, the researchers report that women with estrogen negative tumors were 91 percent more likely to die from breast cancer if they did not receive radiation therapy after a lumpectomy.

Given the relatively recent developments in radiation therapy (i.e., an increased use of brachytherapy and external beams) and data supporting the idea that radiation isn't necessary for women with estrogen positive tumors, researchers wanted to see how actual practice patterns were impacted.

Researchers found that there was a modest increase in the percentage of women with estrogen receptor positive cancers who did not get radiation therapy starting around 2004, and increasing use of radioactive implants, such the MammoSite, Contura, Savi or similar devices, since 2002.

There was also a corresponding drop in women who received external beam radiation, according to Xinglei Shen, M.D., a resident in the Department of Radiation Oncology at Thomas Jefferson University Hospital. "Among women with estrogen receptor negative cancers, there was not the same increase in frequency of women who did not get radiation, but there was an increased use of radioactive implants," he said.

The consequence of those findings was determining what impact omitting radiation has on survival. While there is data that the omission of radiation therapy in women with estrogen receptor positive tumors who receive endocrine therapy, such as Tamoxifen, is not associated with a survival difference, limited data exists for estrogen receptor negative tumors in older women who undergo breast conservation.

"From the randomized trial data, we know that women with estrogen receptor positive stage I breast cancer have no detriment to survival by avoiding radiation, as long as they took Tamoxifen," Dr. Shen said. "However, it is unknown if this would be the case in women with estrogen receptor negative cancer."

Dr. Shen worked with Jefferson Medical College student Andrzej Wojcieszynski to examine survival in these women, and found that they were 91 percent more likely to die from breast cancer if they did not receive radiation therapy after a lumpectomy. (Abstract #1037).

"We have to be cautious when interpreting survival data from the SEER because of potential confounding variables, such as the health of the patients and use of chemotherapy," Dr. Shen said. "However, these data do raise hypotheses for future study."

"Our conclusion is that adjuvant radiation therapy after lumpectomy reduces breast cancer mortality in women over 70 with stage I, estrogen receptor negative breast cancers, and that radiation is currently underutilized in these women," said Wojcieszynski.

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C-reactive protein levels predict breast cancer survival rates, study finds

ScienceDaily (June 1, 2011) — Levels of C-reactive protein (CRP) are increased in response to acute inflammation, infection and tissue damage. There are also reports that CRP levels are elevated because of cancer. New research published in BioMed Central's open access journal Breast Cancer Research shows that elevated CRP levels are predictive of a poor prognosis for breast cancer sufferers.

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C-reactive protein is produced by the liver, in response to infection or injury, when stimulated by the cytokine IL-6. Tumor sites are often associated with inflammation and this inflammation contributes to tumor growth, invasion and metastasis. While elevated CRP has been found associated with a poor outcome for many solid tumors, including endometrial, cervical, prostate and colorectal cancer, there has been some discussion about whether this is true for breast cancer.

Researchers from Denmark looked at data from over 2000 breast cancer patients and followed their progress for up to seven years from diagnosis (average follow up was three years). The researchers found that regardless of lifestyle, menopause status and presence of cardiovascular disease, increasing levels of CRP resulted in increasingly poor prognosis. The five-year survival decreased from 90% for low CRP to 74% for high levels of CRP, disease-free survival reduced from 87% to 74%, and deaths from breast cancer increased from 11% to 20%.

Dr Kristine Allin, from Herlev Hospital, said, "Elevated CRP at time of diagnosis remained predictive of overall survival rates regardless of patient's age, tumor size, lymph node status, or presence of metastasis, and whether or not the patient was estrogen receptor positive. It was still true even when we excluded patients which we believed to have bacterial infections because of their very high CRP levels."

Dr Allin continued, "While measuring CRP levels gives a general indication of health and longevity, measuring CRP levels for breast cancer patients seems to be an easy way to predict the severity of the patient's disease. This may allow clinicians to alter their treatment tactics and improve cancer survival rates."

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No tie found between PTEN and response to breast cancer drug herceptin, according to new study

ScienceDaily (June 3, 2011) — Contrary to what many oncologists had thought, a tumor suppressor protein known as PTEN does not reduce the effectiveness of the breast cancer drug herceptin, according to a study by Mayo Clinic and North Central Cancer Research Group (NCCTG) investigators.

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The study, which looked at tumors from 1,802 patients enrolled in the NCCTG N9831 clinical trial, found that patients with HER2-positive breast cancer and had either a loss of PTEN functioning or normal PTEN activity did equally well when herceptin was added to chemotherapy to prevent breast cancer recurrence.

The researchers presented their findings during the American Society of Clinical Oncology Annual Meeting in Chicago.

"This is the largest study to date evaluating PTEN's presence or loss in the context of antiHER2 therapy, and we found no connection," says the study's lead investigator, oncologist Edith Perez, M.D., director of the Breast Clinic at Mayo Clinic in Jacksonville, Fla., and the Serene M. and Frances C. Durling Professor. "Our research team is very pleased to be able to test an important question in treatment of breast cancer and arrive at a definitive answer."

The researchers stained the samples for PTEN expression and linked that data with disease-free survival. They found that PTEN status did not impact disease-free survival significantly; there was only a slightly greater benefit of adding herceptin for patients with PTEN-tumors.

Preclinical studies and some small patient studies had suggested that tumors with loss of PTEN expression would not benefit from herceptin, Dr. Perez says. As a result, investigators were considering using PTEN biomarkers in clinical studies as a test of herceptin resistance, and patients who tested positive for PTEN loss might then be offered other therapies, or invited to participate in clinical trials.

"We have all been interested in biomarkers that predict for benefit to antiHER2 therapy," Dr. Perez says, "but PTEN is not one that we should pursue further, based on our rigorous analysis."

The tumor samples examined in the study came from NCCTG N9831, a phase III randomized, multicenter clinical trial that tested adjuvant herceptin given with, or following, chemotherapy with paclitaxel, compared with chemotherapy alone.

The study was funded by the National Cancer Institute, the National Institutes of Health and Genentech. The study includes 16 co-authors; nine are from the Mayo Clinic campuses in Florida, Minnesota, and Arizona.

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Breast cancer linked to obesity gene, new research suggests

ScienceDaily (May 23, 2011) — New research aimed to better identify the genetic factors that lead to breast cancer has uncovered a link between the fat mass and obesity associated gene (FTO) and a higher incidence of breast cancer. According to the study conducted at Northwestern Memorial Hospital, people who possess a variant of the FTO gene have up to a 30 percent greater chance of developing breast cancer. Research to identify why the link exists is ongoing, but experts say the finding takes us one step closer to personalized medicine based on genetic risk which would allow for better monitoring and prevention of illness, as well as targeted treatment.

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"This is a fascinating early finding, which fits with the known connections between obesity and breast cancer," said Virginia Kaklamani, MD, oncologist at Northwestern Memorial, co-director of the Cancer Genetics Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and lead author of the study.

Each individual carries the FTO gene, but only 18 percent have this variant of the gene. Kaklamani, who specializes in cancer genetics, says testing for the FTO variant is not available currently, but it may be available in the future, similar to how genetic testing for the BRCA gene mutation exists today.

"Ten years ago we didn't know about the BRCA gene mutation which has been linked to breast and ovarian cancer. Today, we offer genetic testing and a specialized clinic for those at risk in order to minimize their risk and detect any indication of cancer early," said Kaklamani, who is also an associate professor of medicine at Northwestern University Feinberg School of Medicine. "This knowledge helps us better identify who is at an increased risk so one day, we can counter that risk through preventative measures and advanced screening."

The research, published in BMC Medical Genetics is part of an ongoing group of studies to further knowledge of genetic risk factors for breast cancer.

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Lipofilling may be safe during conservation treatment for breast cancer, study suggests

ScienceDaily (May 24, 2011) — A new study has gone some way to answering the question about whether or not a technique called lipofilling is safe for women who are having their breasts reconstructed after surgery for breast cancer.

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Lipofilling involves taking some fat from another area of a woman's body, such as her abdomen, and using it to fill in small defects or asymmetry that may occur during breast reconstruction. However, until now, there has been a lack of evidence as to whether or not the technique could trigger a recurrence of the original breast cancer, and so plastic surgeons have not been able to advise patients fully on the pros and cons of lipofilling, despite the fact that it has been used for over 30 years.

Now, a study published in the cancer journal Annals of Oncology suggests that lipofilling seems to be a safe procedure for breast cancer patients, although the authors say that longer follow-up and more research is required in order to confirm their findings.

The researchers analysed data on 321 women who had been operated on for primary breast cancer at the European Institute of Oncology (IEO) in Milan, Italy, between 1997 and 2008, and who had then had lipofilling as part of their breast reconstruction. These women were matched with double the number (642) of women who had also had surgery for primary breast cancer, but who did not undergo lipofilling.

The researchers followed up the women for an average of 56 months from the time of the primary surgery and 26 months from the lipofilling. They found that eight women in the lipofillling group and 19 women in the control group had a local recurrence of their cancer -- a difference that was not statistically significant. When they analysed the data to look specifically at recurrences in women with non-invasive cancer (in situ cancer) they found there were three cases of recurrence in the lipofilling group and none in the control group; this was statistically significant, but may have been affected by the very small numbers involved, the short follow-up and the fact that there were no recurrences in the control group despite previous research suggesting there should be an average recurrence rate of over two percent during this period of time. "This indicates there might have been some bias in the selection of the women with non-invasive breast cancer in the control group," explained one of the authors, Professor Jean Yves Petit.

Prof Petit, from the Division of Plastic Surgery at the IEO in Milan, said: "To date, only a few studies have focused on cancer recurrences after lipofilling, and this is the first case-control study to investigate the question and the first publication to show the safety of the procedure. Our overall results do not find any difference in recurrences between the women in the lipofilling and control groups. However, it is still too early in the follow-up to be able to draw any definitive conclusions. We urge other teams working in the same field to gather their own results concerning local recurrences after lipofilling in breast conservation treatment."

This study is important because other, experimental work in the laboratory has shown that fatty tissue is capable of producing growth factors that can trigger cancer cells to multiply. This raised the question of whether this might happen in humans.

"Work by other researchers has shown that secretions from transplanted fat tissues can stimulate angiogenesis

Cancer scientists discover new way breast cancer cells adapt to environmental stress

ScienceDaily (May 14, 2011) — An international research team led by Dr. Tak Mak, Director, The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital (PMH), has discovered a new aspect of "metabolic transformation," the process whereby tumour cells adapt and survive under conditions that would kill normal cells.

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The findings, published May 15 in Genes and Development, show how breast cancer cells can thrive when deprived of their usual diet of glucose (sugar) and oxygen by turning to fatty acids for energy generation.

"Our results demonstrate that a protein not previously associated with breast cancer is involved in helping these cells to adapt to starvation conditions and to continue their uncontrolled growth," says Dr. Mak, principal investigator and Weekend to End Breast Cancer Chair in Breast Cancer Research at PMH. Dr. Mak is also a Professor at the University of Toronto in the Departments of Medical Biophysics and Immunology.

In the lab, researchers used an anticancer drug called rapamycin to block a molecular signalling pathway within breast cancer cells that stimulates sugar metabolism. However, instead of dying of starvation, the cells continued to multiply. The team also observed an increase in these cells of carnitine palmitoyltransferase 1C (CPT1C), a protein usually found only in the brains of healthy individuals. Moreover, cells engineered to produce high levels of CPT1C were also able to adapt their metabolism as a survival technique.

"In other words," says Dr. Mak, "The cancer cells acted like cheaters on a diet and found a new food source in fatty acids.

"The fact that CPT1C becomes expressed under conditions of metabolic stress highlights the resilience of cancer cells. They are able to adapt to environmental challenges and find alternative sources of food in order to flourish where healthy cells would not survive."

"Our discovery that deprivation of either sugar or oxygen spurs CPT1C expression in tumour cells marks this protein as a potential target for new drug development," says Dr. Mak.

"We also demonstrated that cells that were prevented from using CPT1C to cope with a disruption in sugar metabolism became more sensitive to environmental stress. These findings represent an important stepping stone to developing targeted therapies that can block cancer cells from adapting to environmental challenges and surviving efforts to kill them."

This most recent discovery builds on Dr. Mak's impressive body of work, which has led to important breakthroughs in immunology and our understanding of cancer at the molecular level. Dr. Mak is known for his 1984 landmark scientific paper on the cloning of the genes for the T cell receptor, a key component of the human immune system.

The research published May 15 was financially supported by grants from the Canadian Institutes of Health Research, The Princess Margaret Hospital Foundation, The Canadian Cancer Society, the Forschungskredit of the University of Zurich and Oncosuisse.

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New biomarker predicts breast cancer relapse

ScienceDaily (May 16, 2011) — Researchers from Virginia Commonwealth University Massey Cancer Center have discovered a new biomarker related to the body's immune system that can predict a breast cancer patients' risk of cancer recurrence. This breakthrough may lead to new genetic testing that further personalizes breast cancer care.

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The study, published in the journal Breast Cancer Research and Treatment, is the first to use tumor infiltrating immune cells located at the site of the tumor to predict cancer recurrence. Using tissue samples from breast cancer patients, researchers found that a specific, five-gene signature related to tumor infiltrating immune cells can accurately predict relapse-free survival. Currently, there are two main tests used to predict the risk of relapse in breast cancer patients, the Oncotype DX panel and the MammaPrint panel. Both of these tests focus on genes that are mainly expressed by tumor cells.

"We know that the body initiates an immune response when it detects cancer, and immune system cells are usually present at the site of the tumor," says the study's lead researcher, Masoud Manjili, D.V.M., Ph.D. assistant professor of microbiology and immunology at VCU Massey. "Our test differs from currently-used tests by looking for a biological response to the presence of cancer, and not relying on genes expressed by the actual cancer cells."

Tissue specimens were collected from female breast cancer patients and maintained in the VCU Massey Cancer Center Tissue & Data Acquisition and Analysis Core (TDAAC) over the past seven years. "We studied data from 17 patients. Of these patients, we had eight that relapsed within five years and nine that have remained cancer-free up to seven years," says Manjili. The five-gene signature was found to predict relapse in these patients with over 85 percent accuracy.

Manjili and his team will next study tissue samples from a larger patient sample to further validate the findings in this study. They also intend to test their findings in a long-term study of breast cancer patients undergoing treatment.

"Our findings could lead to clinical trials that test whether using immunotherapy prior to conventional treatments in breast cancer patients with a high risk of relapse could prime the patients' immune system, much like a vaccine, to prevent the likelihood of relapse," says Manjili.

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Breast cancer: New treatment avenue identified

ScienceDaily (May 17, 2011) — Researchers at the CHUM Research Centre (CRCHUM) and the Peter MacCallum Cancer Centre in Australia have identified a new avenue for treating breast cancer.

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In 20 to 30% of breast cancer patients, the over-expression of a particular protein (human epidermal growth factor-2) is the main cause of the proliferation of cancer cells. Over the past few years Herceptin® (trastuzumab) has become the standard treatment for this kind of cancer. While it is known that it blocks the activity of this protein, its exact mechanism of action has remained a mystery.

Professor John Stagg, a CRCHUM researcher, Professor Mark J. Smyth, with the Peter MacCallum Cancer Centre in Australia, and their colleagues have discovered that in addition to blocking cell proliferation, Herceptin also stimulates the production of interferons, which in turn activate immune cells called lymphocytes.

This study further supports the view that the presence of lymphocytes in tumours enhances treatment success. In addition to revealing the precise workings of Herceptin, this study also showed that combining Herceptin with a therapy that stimulates lymphocytes greatly increases its efficacy in animals.

"These findings open another avenue for breast cancer treatment for nearly a third of all women who are affected," notes Professor Stagg, who is also affiliated with the Faculty of Pharmacy at the University of Montreal and with the Institut du Cancer de Montréal. Clinical trials could get underway in the near future and pave the way for more targeted therapies.

This study was conducted in collaboration with the Peter MacCallum Cancer Centre, East Melbourne, Australia; Jules Bordet Institute, Brussels, Belgium; University of Melbourne, Australia; and Juntendo University, Tokyo, Japan;

The study was funded by the National Health and Medical Research Council of Australia, the Susan Komen Breast Cancer Foundation and the Victoria Breast Cancer Research Consortium (Australia).

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Important step towards early detection of breast cancer

ScienceDaily (May 18, 2011) — European researchers have developed a clinical PET system with the highest resolution and sensitivity in the market, specifically dedicated to breast cancer detection in early stages. The MAMMI (MAMmography with Molecular Imaging) device will allow doctors to start treatments one or even two years earlier than usual and also evaluate the patient's response to chemotherapy.

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Coordinated by José María Benlloch, researcher of the Spanish National Research Council (CSIC) and co-director of the Institute for Molecular Imaging Instrumentation (I3M), the MAMMI Project was created by a multidisciplinary team of eight European research institutions and companies, ranging from medical oncology and pharmacokinetics research to molecular imaging instrumentation, advanced image processing software and integrated electronics circuit design.

The device is currently installed in the National Cancer Institute in Amsterdam (Netherlands) and was previously set up at the clinic of the Technical University of Munich (Germany), where they have completed the clinical research and examined over fifty patients. The new system will shortly be installed in the Provincial Hospital of Castellón (Spain) and other international hospitals have shown their interest in purchasing it.

The most striking novelty of the mammogram is the way it captures the image. The patient lies face down on a special table, and enters a breast in one of the openings. Beside the stretcher, the specialist positions a trolley that incorporates the detection system based on a gamma ray sensor.

The picture is taken without compressing the breast thanks to the ring shape of the detector that surrounds the pendant breast. According to Dr Benlloch: "This significantly improves the visualisation and diagnosis because sometimes there are tumours that are very close to the base of the pectoral muscle."

This new mammogram also provides greater patient comfort. In this sense, the Biomechanics Institute of Valencia (IBV) assessed the company ONCOVISION in the design, manufacturing, and mechanical tests of the stretcher, and applied user-friendly design methodologies and ergonomic criteria. For example, lifting columns were added to the table to facilitate its use by the elderly and disabled.

The PET system

The other major innovation is the technique used. The traditional mammogram is an x-ray of mammary glands. MAMMI, however, is based on the PET technique (Positron Emission Tomography) for the diagnosis of breast cancer, which offers numerous advantages.

In the first stages of a cancer, the malignant cells replicate in an uncontrolled way and, after one to two years, cause a lesion that is visible with the current techniques. After that, the lesion extends and takes about another year until it can be felt.

While current diagnostic equipment is based on morphological images and does not recognize the cancer until there is a lesion, the MAMMI PET measures the metabolic activity of the tumour by locating the high glucose uptake of the cancer cells. This allows the specialist to detect the disease much earlier and numerous studies have confirmed that early detection reduces mortality by 29%.

Until now, whole-body PET scans were indicated for breast cancer patients or for people with a high risk of suffering the disease. However, the result is a low resolution image and therefore does not detect small tumours. "Our device, however, is devoted exclusively to breasts so the detectors are very close to this part of the body and show tumours in early stages," explains Luis Caballero, head of the project in ONCOVISION.

In comparison, MAMMI can see lesions as little as 1.5 mm, while the best of the systems that currently exist offers a resolution of 5 mm. The system generally improves the diagnosis of all patients, but it is especially effective for women with breast implants or young women whose breast density has always made obtaining a clear image difficult.

Assessment in later stages

The mammography device marketed by the Valencian company can also monitor whether the treatment the patient with breast cancer is following actually works. According to Dr Caballero: "By showing the uptake of glucose, the PET technique is the only one able to reveal whether there are still cancer tissues after an operation, since with the other techniques it is impossible to distinguish tumour tissue from the scar left by the operation."

Also, the PET reveals whether the therapies of radiation and chemotherapy are effective or need to be modified. As MAMMI is a more precise PET instrument, it ensures a better assessment of tumour activity and its response to therapy.

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Marker identifies breast cancer patients likely to respond to tamoxifen

ScienceDaily (May 22, 2011) — Cancer researchers at the Kimmel Cancer Center at Jefferson and an international team of collaborators have discovered a biomarker in breast cancer that may help identify which women will respond to anti-estrogen therapy.

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The research appears in the May 16 online issue of the Journal of Clinical Oncology.

Anti-estrogen drugs, most notably tamoxifen, are widely used in patients diagnosed with estrogen receptor-positive breast cancer. However, as many as a third of the women given tamoxifen fail to respond.

In this new study, the investigators found that women whose tumors retain the active form of the protein biomarker Stat5 have an increased likelihood of responding to tamoxifen. In contrast, women treated with tamoxifen whose tumors lacked active Stat5 had up to a 20-fold increased risk of dying from breast cancer after adjustment for effects of standard hormone receptor markers and other pathology data.

"Identification of predictive biomarkers present in breast cancer will lead to improved individualized therapies tailored specifically towards each woman's cancer," said Hallgeir Rui, M.D., Ph.D., professor of oncology, Kimmel Cancer Center at Thomas Jefferson University, and principal investigator of the study. "Absence of the active form of Stat5 could help identify a group of patients unlikely to respond to tamoxifen so they may be offered alternative and more aggressive treatments."

Stat5 protein is a DNA-binding factor that regulates expression of certain genes, many of which remain unknown. During pregnancy, Stat5 is activated by the hormone prolactin, and stimulates milk production in the breast. Active Stat5 is also detectable at lower levels in healthy breast tissue of non-pregnant women. This study further showed that active Stat5 was lost in the majority of more aggressive tumors and when those tumors metastasized to lymph nodes.

In 2004, Rui and colleagues reported that women with early stage breast cancer had higher survival rates when their tumors expressed active Stat5. Therefore, in two independent groups of breast cancer patients that were not treated with chemotherapy or anti-estrogen therapy, they further investigated the relationship between active Stat5 in the tumor and whether the patient had breast cancer recurrence or died of breast cancer over periods as long as 30 years. The team found consistent favorable breast cancer outcomes when tumors retained active Stat5.

The studies presented in this publication utilized a retrospective analysis of five large, independent breast cancer patient materials that included 1,000 patients, giving the studies a solid statistical basis. A benefit of optimizing a marker like Stat5 is that the assay for Stat5 is simple, inexpensive, and can be rapidly adapted to routine analysis in pathology laboratories using standard procedures.

"More work remains to be done, but we are optimistic about the utility of Stat5 as a biomarker," said Amy Peck, PhD, and lead author of the study. "The team is moving forward with plans for a randomized, prospective study with larger patient numbers to further evaluate the utility of Stat5 in managing and treating breast cancer."

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Enzyme may drive breast cancer growth

ScienceDaily (May 20, 2011) — A recently discovered enzyme drives the production of a potent form of estrogen in human breast cancer tissue, researchers from the University of Illinois at Chicago College of Medicine have found.

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The extra-strength estrogen, called estradiol, then drives the production of even more enzyme, in what may be a lethal feed-forward mechanism. Estradiol has been implicated in exacerbating tumor growth in breast cancer.

The research is published in the May issue of the journal Molecular Endocrinology.

Scientists had observed the increased production of an unknown protein in ovarian tissue in response to estrogen. UIC researchers under the direction of Geula Gibori, UIC professor of physiology and biophysics, then purified the protein and cloned its gene. Several laboratories established that it is an enzyme that converts a weak estrogen, estrone, to the much more potent estradiol.

The UIC researchers then examined the production of the enzyme in a line of breast cancer cells known to respond to estrogen levels.

"Estradiol up-regulates the very enzyme that produces estradiol, creating a positive cycle where this potent form of estrogen is being produced over and over again, sustaining its own production," said Aurora Shehu, UIC postdoctoral research associate in physiology and biophysics and first author of the study.

In human breast tissue, the researchers found a "dramatic" up-regulation in the cancerous cells but not in the surrounding benign tissue, said Gibori, who is principal investigator on the study. The surrounding tissue, however, is a rich source of the estrone that the enzyme needs to produce more estradiol, she said.

The researchers were able to show how estradiol turns on the gene that produces the enzyme, and that this activation also required at least one other known regulatory factor.

They found that tamoxifen, a drug widely used to inhibit breast cancer growth, prevents estradiol's stimulation of the enzyme and thus may shut down local production of estradiol in breast cancer cells.

"Breast cancer tumors with this enzyme are likely to be a much more aggressive and potentially deadly type of cancer," Gibori said. "Identifying this enzyme and how its expression is turned on gives medical researchers potential targets for disrupting the lethal production of estradiol in breast cancers."

The enzyme is a promising therapeutic target because blocking it may halt production only of the dangerous estradiol, which would reduce the side effects seen with other drugs that inhibit production of many estrogen-related compounds, Gibori said.

This study was supported by grants from the National Institutes of Health. Y. Sangeeta Devi, Kristin Luther, Julia Halpern, Jamie Le, Jifang Mao, Rachel Duan and Jonna Frasor from UIC and Constance Albarracin of the University of Texas, Houston, also contributed to the study.

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Yoga improves quality of life in women with breast cancer undergoing radiation therapy, study finds

ScienceDaily (May 18, 2011) — For women with breast cancer undergoing radiation therapy, yoga offers unique benefits beyond fighting fatigue, according to new research from The University of Texas MD Anderson Cancer Center.

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While simple stretching exercises improved fatigue, patients who participated in yoga that incorporated yogic breathing, postures, meditation and relaxation techniques into their treatment plan experienced improved physical functioning, better general health and lower cortisol (stress hormone) levels. They also were better able to find meaning in their cancer experience.

The findings, to be presented next month in an oral session at the 47th annual meeting of the American Society of Clinical Oncology by Lorenzo Cohen, Ph.D., professor and director of the Integrative Medicine Program at MD Anderson, are the latest in an ongoing effort to scientifically validate the age-old belief that mind-body interventions have a beneficial impact on the health of cancer patients. The research was conducted in collaboration with India's largest yoga research institution, Swami Vivekananda Yoga Anusandhana Samsthana in Bangalore, India.

The study assessed, for the first time, yoga benefits to cancer patients by comparing their experience with patients in an active control group who integrated simple, generic stretching exercises into their lives. "The combination of mind and body practices that are part of yoga clearly have tremendous potential to help patients manage the psychosocial and physical distress associated with treatment and life after cancer, beyond the benefits of simple stretching," said Cohen.

To conduct the study, 163 women with breast cancer (stage 0-3) averaging 52 years of age were randomized to one of three groups: 1) yoga; 2) simple stretching; or 3) no instruction in yoga or stretching. Participants in the yoga and stretching groups attended sessions specifically tailored to breast cancer patients for one hour three days a week throughout their six weeks of radiation treatment.

Participants were asked to report on their quality of life, including fatigue, daily functioning, benefit finding, depression and spirituality. Saliva samples were collected and electrocardiogram tests were administered at baseline, end of treatment, and at one, three and six months post-treatment.

After completing radiation treatment, only the women in the yoga and stretching groups reported a reduction in fatigue. At one, three and six months after radiation therapy, women who practiced yoga during the treatment period reported greater benefits to physical functioning and general health. They were more likely to perceive positive life changes from their cancer experience than either other group.

Women who practiced yoga also had the steepest decline in their cortisol across the day, indicating that yoga had the ability to regulate this stress hormone. This is particularly important because higher stress hormone levels throughout the day, known as a blunted circadian cortisol rhythm, have been linked to worse outcomes in breast cancer.

According to Cohen, developing a yoga practice also helps patients after completing cancer treatment. "The transition from active therapy back to everyday life can be very stressful as patients no longer receive the same level of medical care and attention. Teaching patients a mind-body technique like yoga as a coping skill can make the transition less difficult."

Through a grant from the National Cancer Institute -- the largest ever awarded for the study of yoga in cancer -- Cohen and his team will next conduct a Phase III clinical trial in women with breast cancer to further determine the mechanisms of yoga that lead to improvement in physical functioning, quality of life, and biological outcomes during and after radiation treatment. A secondary aim of the trial, but one of great importance, stressed Cohen, is assessing cost efficiency analysis for the hospital, health care usage costs in general, and examining work productivity of patients.

MD Anderson recognizes the growing body of research indicating that relaxation-based interventions can contribute to the well-being of people with cancer. Through the Integrative Medicine Program, complementary therapies, such as yoga, are offered at MD Anderson's Integrative Medicine Center, and are used in concert with mainstream care to manage symptoms, relieve stress, enhance quality of life, and improve outcomes for patients and their caregivers. MD Anderson's Integrative Medicine faculty also conduct research in the biological and behavioral effects of mind-body based interventions; the anti-cancer potential of natural compounds; and, acupuncture to treat common cancer treatment-related side effects.

In addition to Cohen, other MD Anderson researchers contributing to this study include: Kavita Chandwani, M.D., former senior research coordinator and yoga teacher; Robin Haddad, M.P.H. , research coordinator, George Perkins, M.D. in the Department of Radiation Oncology; Amy Spelman, Ph.D., Kayla Johnson, B.S. and Adoneca Fortier, B.S., all staff in the Integrative Medicine Program; Banu Arun, M.D., in the Department of Breast Medical Oncology; and Qi Wei, M.S., Sr. Statistical Analyst. Clemens Kirschbaum, Ph.D. contributed from the Technical University of Dresden, Dresden, Germany. Collaborators from SVYASA include NV Raghuram, B.E.; R. Nagarathna, M.D., and HR Nagendra, Ph.D., founder.

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