Clues to cancer metastasis: Discovery points to potential therapies for bone metastasis

ScienceDaily (Oct. 11, 2012) — In recent years investigators have discovered that breast tumors are influenced by more than just the cancer cells within them. A variety of noncancerous cells, which in many cases constitute the majority of the tumor mass, form what is known as the "tumor microenvironment." This sea of noncancerous cells and the products they deposit appear to play key roles in tumor pathogenesis.
Among the key accomplices in the tumor microenvironment are mesenchymal stem cells (MSCs), a group of adult progenitor cells which have been shown to help breast cancers maneuver and spread to other parts of the body.
Now, new research sheds further light on how this is happening. Led by investigators at Beth Israel Deaconess Medical Center (BIDMC), the findings demonstrate that the lysyl oxidase (LOX) gene is spurred to production in cancer cells as a result of their contact with MSCs, and once produced, can help ensure the spread of otherwise weakly metastatic cancer cells from primary tumors to the lung and bones. Described on-line in the Proceedings of the National Academy of Sciences
(PNAS), this discovery not only provides key insights into the basic biology of tumor formation, but also offers a potential new direction in the pursuit of therapies for the treatment of bone metastasis.
"We don't have a lot of therapies that can target breast cancer once it has metastasized, particularly once cancer cells have lodged in the bone," says senior author Antoine Karnoub, PhD, an investigator in the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School. "When breast cancer cells reach the skeleton, one way in which they cause damage is by breaking down bone tissue, which results in the bone's rich matrix releasing numerous factors. These factors, in turn, feed the cancer cells, setting in motion a vicious cycle that leaves patients susceptible to fractures, pain, and further metastasis."
MSCs are non-hematopoietic progenitor cells predominantly produced in the bone marrow that generate bone, cartilage, fat, and fibrous connective tissue. They additionally support immune cell development and are recruited to inflammatory sites throughout the body to help shut down immune responses and regenerate damaged tissues, as might occur during wound healing. Several years ago, as a postdoctoral researcher at the Whitehead Institute of the Massachusetts Institute of Technology, Karnoub began exploring the idea that MSCs were migrating to tumors after mistaking the cancer sites for inflammatory lesions in need of healing.
"We discovered that once MSCs had reached the tumor sites, they were actually helping in cancer metastasis, causing primary cancer cells to spread to other sites in the body," he explains. In this new paper, Karnoub wanted to find out, in greater molecular detail, how breast cancer cells respond to the influences of MSCs in order to better understand how cancer cells cross-talk with recruited cells in the microenvironment.
His scientific team first embarked on a straightforward experiment. "We took two dishes of cells, cancer cells and MSCs, and mixed them together," explains Karnoub. After three days, they removed the cancer cells and studied them to see how they had changed.
"We found that the lysyl oxidase [LOX] gene was highly upregulated in the cancer cells," he says. "It turns out that when a cancer cell comes in contact with an MSC, it flips on this LOX gene, turning it up by a factor of about 100. So our next question was, 'What happens to the cancer cells when they encounter this boost of LOX that they themselves have produced?'"
The answer, as revealed in subsequent experiments, was that LOX was setting in motion a cell program called epithelial-to-mesenchymal transition (EMT). During EMT, cancer cells that usually clump together undergo a transformation into cells that exhibit decreased adhesion to their neighbors and go their own way. As a result, these cancerous cells are able to migrate, significantly enhancing their ability to metastasize.
"When we put these cells back into mice, they not only formed tumors that metastasized to the lung, but also to the bone," says Karnoub. "This makes you wonder whether the cancer cells in primary tumors have become so acclimated to interacting with bone-derived MSCs that they can now grow more easily in the bone once they leave the tumor."
The investigators also wanted to find out if, by going through the EMT process, cancer cells were also acquiring the phenotypes of another highly aggressive feature of malignant cancer cells, those of cancer stem cells within the cores of most tumors.
"Cancer stem cells are believed to be responsible for the resurgence of tumors following chemotherapy treatment, and an increasing body of science is focused on understanding how CSCs function and how they originate," says Karnoub. "The processes of EMT and CSC formation have been described as being closely coupled and we asked whether LOX might be regulating CSC phenotypes, just as it was regulating EMT. To our surprise, this was not the case. This tells us that pathways that were once thought to be intimately intertwined and commonly tweaked may, in fact, be separate, and now we can start to tease out the respective circuitries with a bit more clarity."
Lastly, the investigators identified the mechanism that was enabling LOX to be turned on from outside the cell, a set of molecules called hyaluronic acid (HA) and CD44. "It turns out that the MSCs provide the HA while the cancer cells provide the CD44 and they work in tandem like a lock and key to upregulate LOX expression," explains Karnoub, adding that antagonists to HA and CD44, already in extensive investigations and clinical exploration, might be of increased use from a clinical standpoint, perhaps in managing bone metastasis.
"This work reveals yet another important component of the complexity of malignant progression," says Robert Weinberg, PhD, Professor of Biology and Director of the MIT Ludwig Center for Molecular Oncology at the Massachusetts Institute of Technology. "The bidirectional communication between breast cancer cells and the nearby MSCs results in the acquisition of malignant traits by cancer cells, including their spread to distant sites in the body where they seed potentially lethal metastases."
Says Karnoub, "Now that the functions of tumor promoters and tumor suppressors are being appreciated with increased clarity, it would aid greatly if we can understand how these major cancer regulators are themselves regulated by what's outside the cancer cell. In concert with designing therapies that can enter inside the cell to directly inhibit such active players, one could perhaps design a therapy that inhibits the interaction of the cancer cell with its microenvironment, thereby shutting off the desired pathways altogether."
Study coauthors include BIDMC investigators Christelle P. El-Haibi (first author), Antoine Campagne, Anthony Y. Collmann, and Eva Csizmadia; George W. Bell of the Whitehead Institute for Biomedical Research; Jiangwen Zhang of the Faculty of Arts and Sciences, Harvard University; David Wood and Sangeeta N. Bhatia of the Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; Cally M. Scherber, Mehmet Toner and Daniel Irimia of Massachusetts General Hospital; and Odette Mariani and Anne Vincent-Salomon of the Institut Curie, Paris, France.
This work was supported by grants from the National Institutes of Health (R21CA135601) and startup funds from BIDMC and the Sidney Kimmel Cancer Research Foundation. Antoine Karnoub is a 2010 Kimmel Scholar and a recipient of a 2012 Career Catalyst Research Award from Susan G. Komen for the Cure.
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Journal Reference:
C. P. El-Haibi, G. W. Bell, J. Zhang, A. Y. Collmann, D. Wood, C. M. Scherber, E. Csizmadia, O. Mariani, C. Zhu, A. Campagne, M. Toner, S. N. Bhatia, D. Irimia, A. Vincent-Salomon, A. E. Karnoub. Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1206653109
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Increased colorectal cancer risk for extended family members

ScienceDaily (Oct. 22, 2012) — Women under age 50 who have been diagnosed with endometrial cancer, and first, second and third degree relatives of patients with colorectal cancer may have an increased risk of developing colorectal cancer (CRC), according to two separate studies unveiled October 22 at the American College of Gastroenterology's (ACG) 77th Annual Scientific meeting in Las Vegas. Two other CRC-related studies presented at ACG 2012 investigated the impact of gender, race and obesity on the incidence of adenoma and advanced adenoma detection rates -- suggesting that overweight African American and Hispanic men may be at greater risk for precancerous polyps which if not detected early enough could lead to colorectal cancer.

Highlights of Colorectal Cancer Research from the ACG Annual Scientific Meeting

"Risk of Colorectal Cancer after Diagnosis of Endometrial Cancers: A Population-Based Study

"Women diagnosed with endometrial cancer under age 50 had a "marked increased risk" of being diagnosed with colorectal cancer in a historical cohort study by researchers at the University of Manitoba who linked several large longitudinal databases routinely collected in Manitoba, including the Manitoba Cancer Registry and some of Manitoba Health databases. The researchers followed 3,115 women diagnosed with endometrial cancer between 1987 and 2008 and 15,084 age-matched controls up to December 2009.

Women younger than 50 in the cohort at the time of diagnosis of endometrial cancer had an approximately four -fold increased risk of being subsequently diagnosed with colorectal cancer as compared to the age matched women in the general population. The risk was even higher (seven fold higher) for colorectal cancers occurring in the upper part of the colon (right colon). There was no increased risk for colorectal cancer among women diagnosed with endometrial cancer, when they were 50 years old or older.

Endometrial cancer is a cancer that starts in the inner lining of the womb (uterus) called the endometrium. In the U.S., endometrial cancer is the most common cancer found in women's reproductive organs. The chance of a woman having this cancer during her lifetime is about one in 38, according to the American Cancer Society.

"This study suggests there is an increased risk of colorectal cancer after a diagnosis of endometrial cancer among young women," said co-investigator Dr. Harminder Singh. He said, therefore these patients need close follow-up particularly for colorectal cancers occurring in the upper part (right-side) of the colon. "Colorectal cancer screening should start at a younger age in such women."

"Elevated Risk of Colorectal Cancer in Relatives of Patients with Colorectal Cancer: A Population-Based Study in Utah"

In the first population-based assessment of the risk of colorectal cancer in extended family members of patients with CRC, researchers from the Huntsman Cancer Institute in Salt Lake City, UT reported that first, second and third degree relatives of individuals with colorectal cancer had an increased risk of developing CRC themselves -- with the strength of the association based on the degree of kinship, according to lead investigator, Niloy Jewel Samadder, M.D.

The "degree of kinship" describes the proportion of genes shared by two blood relatives. A person's first-degree relative is a parent, sibling, or child. A first degree relative shares about half of their genes with the person. A second degree relative of a person is an uncle, aunt, nephew, niece, grandparent, grandchild or half- sibling. A second degree relative shares about one quarter of their genes with the person; while a third degree relative of a person is a first cousin, great-grandparent or great-grandchild. A third degree relative shares about one eighth of their genes with the person.

"This study has resolved many of the issues confounded in previous studies where reliance on patient recall regarding family history and lack of verification of reported colorectal cancer diagnoses have made it difficult to quantify the risk of CRC in the relatives of patients with colorectal cancer," said Dr. Samadder, noting that the "biggest strength" of the study is its design.

The retrospective case-control study included 126,936 Utah residents between 50 and 80 years old who underwent colonoscopy between February 15, 1995 and January 31, 2009 at Intermountain Healthcare of University of Utah Health System -- with 3,804 of these patients diagnosed with CRC -- and defined as the case population. For each case, 1 randomly selected age-and -sex-matched control was selected from the population who had CRC-free colonoscopy. Researchers confirmed family relationships through the Utah population database and CRC diagnosis through the Utah Cancer Registry. The results showed that first degree relatives of individuals with colorectal cancer had an 80 percent increased risk for CRC; second degree relatives had an increased risk of 30 percent and third degree relatives had an increased risk of 15 percent.

"Our data support the current CRC screening guidelines and raise the question of whether such screening should be extended to first-degree relatives of patients with CRC diagnosed at or above age 60," said Dr. Samadder, adding that the results, "further support a genetic basis of inheritance for CRC over shared environmental factors."

A key message from the study is that "the risk for colorectal cancer doesn't stop at our first-degree relatives," noted Dr. Samadder. He urged patients to be aware of their extended family histories and encouraged physicians to look beyond a patient's parents and grandparents when assessing colorectal cancer risk.

"Impact of BMI and Gender on Advanced Adenoma Detection Rates in Minority Populations" Body mass index (BMI) seems to have a linear association with advanced adenoma detection rates (ADR) in an African American and Hispanic male cohort, where a trend towards higher right-sided advanced adenomas is also seen in this study group, according to researchers from The Brooklyn Hospital Center.

Adenomas are a type of colon polyp that is considered a precursor for invasive colorectal cancer (CRC) which is the third most commonly diagnosed cancer and the second leading cause of cancer death in both men and women in the U.S., according to the American Cancer Society. It is estimated that there will be 143,460 new cases diagnosed in the United States in 2012 and 51,690 deaths due to this disease.

The study included 895 subjects with a mean age of 73 years and a higher proportion of females compared to males. African Americans made up 74 percent of the group and 26 percent were Hispanic. The study subjects were divided into five groups based on BMI, according to co-investigator Shashideep Singhal, M.D., who noted that males showed a progressive linear incremental trend in ADR with an increase in BMI. Total ADR was 14%, 12.9%, 13.9% and 16.3 % in Groups 1-4 with no statistical differences. Group 5 was excluded from analysis due to small sample size. The incidence of right-sided advanced adenomas was also higher with increasing BMI (60%, 60%, 64.3% and 71.4% in Groups 1-4 respectively). However, this trend was not seen in women in this cohort.

"The study shows that the higher the BMI the higher the adenoma detection rate and that African American and Hispanic men in this study group have the greatest risk for pre cancerous polyps which if not detected early could lead to colorectal cancer," said Dr. Singhal." He said that while these findings need to be confirmed with larger studies, they may have useful implications for designing preventive strategies in high-risk populations -- specifically identifying patients who are at high risk and increasing colonoscopy screening intervals in these patients who are at increased risk for CRC.

When detected early, polyps can be removed during a colonoscopy exam, preventing the development of colorectal cancer. This ability to prevent colorectal cancer through polyp removal is the cornerstone of the American College of Gastroenterology's 2009 screening guideline which recommends colonoscopy as a "preferred" colorectal cancer prevention strategy. The ACG also recommends African Americans undergo CRC screening at age 45 due to increased CRC risk factors. A tremendous body of evidence shows that clearing the colon of polyps, including small polyps, significantly reduces colorectal cancer mortality. When detected in its earliest and most treatable stage, the survival rates for colorectal cancer exceed 90 percent.

"Gender Specific Prevalence of Adenomas, Advanced Adenomas and Colorectal Cancer in Patients Undergoing Screening Colonoscopy"

Researchers from The University of Texas Medical Branch collected colonoscopy data retrospectively from a university-based hospital and included all average risk screening colonoscopies performed between 2006 and 2011 to determine and compare the prevalence and numbers needed to screen for adenomas, advanced adenomas and colorectal cancer in different age groups among men and women. Of the 2388 patients included in the study, 51 % were women.

Overall, men in the study group had a significantly higher prevalence of adenomas (32% vs. 23%) and advanced adenomas (8% vs. 5%) compared to women and the prevalence of CRC was higher in men, but did not reach statistical significance, according to co-investigator Dr. Praveen Guturu, MD.

When the data was broken down between different age groups, the prevalence of adenomas in the 50-59 year age group was significantly higher in men compared to women (29% vs. 19%). But there was no statistically significant difference in the prevalence of adenomas and advanced adenomas among men in the 60-69 age group and over 70 group, when compared to women. "Our study suggests that men might develop advanced colon polyps at an earlier age compared to women and this information will help us design appropriate screening and surveillance guidelines in future,'' said Dr Guturu.

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Statins may reduce risk of esophageal cancer

ScienceDaily (Oct. 22, 2012) — Statins, a cholesterol lowering drug may lower the risk of esophageal cancer, especially in patients with Barrett's esophagus, Mayo Clinic researchers report in a study being presented at the American College of Gastroenterology annual meeting.

There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. Barrett's esophagus, a complication of gastroesophageal reflux disease, raises the risk of adenocarcinoma, the more common type of esophageal cancer. Barrett's esophagus is a precancerous condition in which the lining of the esophagus, the tube that carries food from the throat to the stomach, is damaged by stomach acid.

Although still uncommon, adenocarcinoma is on the rise in the United States. About 16,000 people are diagnosed with esophageal cancer annually, of which more than 60 percent are adenocarcinomas. Only 1 in 5 patients with this cancer will still be alive five years after diagnosis.

"Unfortunately, survival rates for this cancer are low, so prevention is critical," says Siddharth Singh, M.B.B.S., a Mayo Clinic gastroenterologist and study author. "So these results are supporting and encouraging, but more research is needed before we recommend that patients at risk of esophageal cancer take statins."

The Mayo study combined data from 13 studies that included over 1.1 million patients, of which 9,285 had esophageal cancer. The analysis found statins lowered cancer risk by nearly one-third; the longer a patient was on statins, the greater the protective effect.

Researchers also looked at aspirin's effect on reducing the risk of esophageal cancer. When researchers looked specifically at Barrett's esophagus, patients taking a statin and aspirin reduced their risk of esophageal cancer by 72 percent.

The results, researchers say, support a protective association between statin use and esophageal cancer. Given the high mortality rates of the cancer, researchers say these results support randomized trials to evaluate statins in patients who are at high risk of developing esophageal cancer.

Along with Barrett's esophagus, other risk factors for adenocarcinoma of the esophagus include male gender, obesity and smoking.

Other study authors include Abha Singh, M.B.B.S.; Preet Paul Singh, M.D.; M. Hassan Murad, M.D.; and Prasad Iyer, M.D.

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Many Lesbians Not Screened for Cervical Cancer, Study Finds

FRIDAY, Oct. 19 (HealthDay News) -- The rate of routine screening for cervical cancer is low among lesbians, according to a new study.

More awareness about screening for this type of cancer among the lesbian community is needed to reduce the risk for the disease in these patients, the researchers said. Specifically, improved communication between patients and their doctors is the key to raising awareness about cancer screenings.

"Despite our knowledge of the value of Pap testing for early detection of treatable cervical abnormalities, lesbians are one subset of women who are not getting screened at recommended rates," said J. Kathleen Tracy, associate professor in the department of epidemiology and public health at the University of Maryland School of Medicine.

"In fact, nearly 38 percent of lesbians in our study had not been screened according to recommended guidelines," Tracy said in a news release from the American Association for Cancer Research.

Often called a Pap smear, the test examines cells scraped from the cervix to look for precancerous abnormalities.

For the study, the researchers sent online surveys on cervical cancer screening to 3,000 women who identified themselves as lesbians. An analysis of more than 1,000 responses revealed that 62 percent of the women had routine screenings. The investigators also found that 17.5 percent of the women said they did not undergo routine screenings because they did not have a physician referral. Meanwhile, just over 17 percent were not regularly screened for cervical cancer because they didn't have a doctor.

After taking into account the women's age, level of education, relationship and employment status, and whether or not the women had health insurance, the study found that women who told their primary care doctor or gynecologist that they were a lesbian were more than twice as likely to be routinely screened for cervical cancer.

"When this finding is coupled with that of the potency of provider recommendation, it underscores how critical effective communication between patient and provider is for optimal health and disease prevention," Tracy said.

The researchers said the women who knew that not having a Pap test is a risk factor for cervical cancer were nearly two times more likely to undergo routine screening for the disease.

"This study highlights an often overlooked cancer disparity," Tracy concluded. "We know that human papillomavirus can be transmitted during same-sex sexual activity, so lesbians are at risk for developing cervical cancer. If this group of women doesn't participate in screening, they are at elevated risk for developing cervical cancer via missed opportunities to identify and treat precursor abnormalities."

The study was scheduled for presentation this week at the annual cancer prevention conference of the American Association for Cancer Research in Anaheim, Calif.

Women should start having Pap tests by age 21, according to the American College of Obstetricians and Gynecologists. How often the screening is performed after that depends on a woman's age and health history.

The data and conclusions of research presented at meetings are typically considered preliminary until published in a peer-reviewed medical journal.

-- Mary Elizabeth Dallas Copyright © 2012 HealthDay. All rights reserved. SOURCE: American Association for Cancer Research, news release, Oct. 17, 2012

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Chronic constipation linked to increased risk of colorectal cancer

ScienceDaily (Oct. 22, 2012) — Patients with chronic constipation may be at increased risk of developing colorectal cancer and benign neoplasms, according to study findings unveiled October 22 at the American College of Gastroenterology's (ACG) 77th Annual Scientific meeting in Las Vegas.

The study, "Risk of Developing Colorectal Cancer and Benign Neoplasm in Patients with Chronic Constipation," investigated the prevalence and incidence of colorectal cancer and benign neoplasms in 28,854 patients with chronic constipation (CC) and 86,562 controls without CC that were identified from a large retrospective U.S. claims database (January 1999-September 2011). Patients with at least two diagnoses of constipation were required to be 18 years or older and continuously enrolled in their health plan for at least one year following the study index date, which was the patient's first eligible diagnosis of constipation. Patients with diagnoses of irritable bowel syndrome or diarrhea were excluded.

Researchers found that:

• Both colorectal cancer (CRC) and benign neoplasms are more prevalent in chronic constipation patients compared to a control population free from chronic constipation.

• Among the patients that were not previously diagnosed with CRC or benign neoplasms prior to their index date, and after controlling for potential confounding factors including age, gender, family history of malignancies, and other non-gastrointestinal comorbidities, patients with CC were more at risk to develop CRC or benign neoplasms.

• The risk of developing CRC was 1.78 times higher for chronic constipation (CC) patients and the risk of developing benign neoplasms was 2.70 times higher. After adjusting for potential confounding factors, which are potentially also associated with the CC conditions, the incremental risk of developing CRC and benign neoplasms remained "consistently high."

"This study demonstrates an association, not causation, between chronic constipation and both colorectal cancer and benign neoplasms" said co-investigator Nicholas Talley, M.D., Ph.D., of the University of Newcastle. "The postulated causal link between constipation and increased colorectal cancer risk is that longer transit times increase the duration of contact between the colonic mucosa and concentrated carcinogens in the lumen, such as bile acids or other carcinogens."

"The association between constipation and colorectal cancer deserves further exploration to better understand possible causal elements," said Dr. Talley. "Moreover, a review of the existing literature suggests prospective cohort studies have not identified this association. Thus, the findings may reflect recall bias."

"In this study, patients with chronic constipation were found to be at increased risk of developing colorectal cancer and benign neoplasms, said Dr. Talley. "Although chronic constipation is considered a relatively benign disease, practitioners should be aware of this potential association to monitor and treat accordingly," said Dr. Talley. "We encourage anyone with questions related to their condition to talk to their health care professional so that the specific health needs of each patient can be balanced with the risks and benefits of medications."

He also noted that further research is warranted to evaluate whether patients who have their constipation well controlled are at lower risk of developing CRC and benign neoplasms. "Longitudinal prospective studies to understand the causal relationship between chronic constipation and CRC would advance our understanding of prevention and management of these disorders."

About Chronic Constipation

Constipation, one of the most common gastrointestinal complaints in the United States, occurs when the colon absorbs too much water or if the colon's muscle contractions are slow or sluggish, causing the stool to move through the colon too slowly. As a result, stools can become hard and dry. More than 4 million Americans have frequent constipation, accounting for 2.5 million physician visits a year, according to the National Digestive Diseases Information Clearinghouse (NDDIC).

Chronic constipation is a condition of infrequent bowel movements -- typically fewer than three bowel movements a week -- and difficult passage of stools which does not go away. In some cases, CC may be caused by an underlying medical condition.

About Colorectal Cancer

Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer death in both men and women in the US, according to the American Cancer Society. It is estimated that there will be 143,460 new cases diagnosed in the United States in 2012 and 51,690 deaths due to this disease. The American College of Gastroenterology's screening guidelines recommend colonoscopy as a "preferred" colorectal cancer prevention strategy beginning at age 50 (age 45 for African Americans.)

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Depression, shortened telomeres increase mortality in bladder cancer patients

ScienceDaily (Oct. 18, 2012) — Low depressive symptoms and a longer telomere length are compelling factors that contribute to a prolonged life for bladder cancer patients, according to researchers at The University of Texas MD Anderson Cancer Center.

In an observational study, a team of MD Anderson researchers analyzed clinical and behavioral data collected from 464 bladder cancer patients, according to research presented at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research.

"This is the first study of its kind that analyzes bladder cancer outcomes," said Meng Chen, Ph.D., an instructor in MD Anderson's Department of Epidemiology. "Psychological factors are not usually included in epidemiologic studies"

The patients observed were enrolled in an ongoing study of bladder cancer that provides extensive genetic, epidemiologic and psychological data. The collaboration of MD Anderson epidemiologists and psychologists is led by the study's principal investigator, Xifeng Wu, M.D., Ph.D., professor and chair of the epidemiology department.

Patients' information was analyzed according to four different groups. The first group involved patients with long telomeres and no depressive symptoms; the second identified patients who had long telomeres with depressive symptoms; the third had shortened telomeres and no depressive symptoms, while the fourth group had shortened telomeres and depressive symptoms.

Bladder cancer is the fourth most common cancer of men and is usually diagnosed in people over the age of 60. The American Cancer Society estimates 56,000 men and 18,000 women will have a bladder cancer diagnosis in 2012.

Research has identified shortened telomere length as an aging-associated biomarker in several diseases, including cancer. As people grow older, telomeres on the tips of chromosomes, which protect chromosomes from unraveling as cells replicate, shorten and eventually fail, leading to cell death. MD Anderson researchers analyzed blood samples to measure telomere length.

Depressive symptoms were analyzed using the Center for Epidemiologic Studies Depression Scale (CES-D). The self-report scale -- one of the most common screening tests used for finding levels of depression -- revealed patients who scored at high levels of depressive symptoms have a 1.89-fold risk of dying compared to those with lower levels of depression, who will live a little over three times longer -- 200 months vs. 58 months.

The study also revealed the combination of factors, longer telomeres and low levels of depressive symptoms, increased survival for bladder cancer patients by more than six-fold -- 31.3 months vs 199.8 months. Those with short telomeres and high levels of depression had a three-fold risk of mortality.

A certain level of stress, which has also been associated with shortened telomere length, is a dominating factor with many cancer patients. "People are not treating the depression directly, but mainly focused on coping with cancer,"said Chen. "This leads to additional stress that increases mortality."

Enhanced stress management should be an integral part of cancer treatment, "Lifestyle behaviors including a healthy diet, regular exercise and smoking-cessation are factors for reducing stress and ultimately depression in cancer patients." " said co-author Jie Lin, Ph.D., assistant professor in the Department of Epidemiology.

Lin also said the new risk factors such as psychological risk factors identified by the team could be included in future risk prediction models. The team is optimistic that this study will encourage clinicians to incorporate behavioral factors into risk models so interventions can be developed to prolong survival for bladder cancer patients.

Contributing authors to the work include Jan Blalock, Ph.D., Paul Cinciripini, Ph.D. from the Department of Behavioral Science, and Lorenzo Cohen, Ph.D., from the Department of General Oncology.

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Cancer diagnosis does not make young people religious, research suggests

ScienceDaily (Oct. 18, 2012) — A sociologist of religion from the University of Copenhagen has interviewed 21 young patients diagnosed with a life-threatening cancer about their religious beliefs. She concludes that a cancer diagnosis will not make young people, who are not religious already, turn to religion. But it can confirm already existing beliefs.

"My research shows that young cancer patients' views on existential issues show consistency before and after the diagnosis: Their faith and their religious practices remain the same. However, the beliefs they already had can be confirmed and strengthened -- this applies both to religion and science -- so the patients may feel more strongly for the beliefs they had before they were diagnosed," explains sociologist of religion Nadja Ausker from the University of Copenhagen.

It has been a theoretical staple of sociology of religion that major religious conversions are preceded by personal crises; a person's feelings toward religion are significantly altered when confronted with an existential crisis such as a cancer diagnosis.

But Nadja Ausker challenges this theory with her thesis "Time for a change? Negotiations of religious continuity, change, and consumption among Danish cancer patients." In the thesis, she interviews 21 young cancer patients about the religious consequences of life crises, both shortly after the diagnosis and during treatment.

No hypocrisy

Nadja Ausker explains that a cancer diagnosis does not make young people lose their religion, just as atheists do not become religious:

"The cancer patients do contemplate existential issues, but that does not mean that they suddenly start praying or going to church if these religious practices were not already part of their lives. Several patients said it would be hypocritical of them to change practice and faith because of the diagnosis."

What the patients who already are religious find important, according to Nadja Ausker, is the availability of religious goods to choose from and consume as needed -- just as one takes a pill or other medication. The patients become "consumers" of religious goods, and they pick the goods for immediate consumption, e.g. prayer or attending a church.

The patients therefore consume religious practices, and not new religious beliefs, during their illness. But their post-diagnosis practices are still consistent with their pre-diagnosis practices.

About the study

Nadja Ausker's PhD thesis is a collaboration between the University of Copenhagen and the largest Danish hospital, Rigshospitalet. It is based on 40 interviews with 21 cancer patients under the age of 40 diagnosed with leukemia or lymphoma. The interviews were conducted 1-6 months and 12-18 after the diagnosis.

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Developed a technology that predicts metastasis in breast cancer

ScienceDaily (Oct. 18, 2012) — Researchers at the Bellvitge Biomedical Research Institute (IDIBELL) and The Institute of Photonic Sciences (ICFO) have collaborated on the development of a diagnostic tool that identifies the metastatic ability of breast cancer cells. The analysis is based on the characterization of the lipid component of the cells, which is indicative of malignancy. This has allowed the researchers to develop a classifier to discriminate cells capable of inducing metastasis.

The results of the study have been published in the online version of the scientific journal PLoS ONE.

The characterization of the lipids associated with malignancy has been possible thanks to the technological development of a spectroscopic device named Raman along with the versatility offered by the experimental models of breast cancer. The results of this process form the basis for introducing this technique in routine cytological diagnosis, which could be extended in the future to diagnose other tumours.

The researchers have analyzed the main components and, partly, the less discriminating ones to assess the profile of the lipid composition of breast cancer cells. They have generated a classification model that segregated metastatic and non-metastatic cells. "The algorithm for the discrimination of the metastatic ability is a first step towards the stratification of breast cancer cells using this quick and reactive tool," explains the study coordinator, Àngels Sierra, researcher at the Biological Clues of the Invasive and Metastatic Phenotype group of IDIBELL.

Using cytology techniques, the researchers have found a correlation between the activation of lipogenesis (the chemical reaction leading to fatty acids in an organism) and the amount of saturated fats in metastatic cells indicating a worse prognosis and a decreased survival. The lipid content of the breast cancer cells might be a useful measure to determine various functions coupled to the progression of breast cancer. The work has been supported by the Instituto de Salud Carlos III, the former Spanish Ministry of Science and Innovation and the private Cellex Barcelona Foundation.

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The above story is reprinted from materials provided by IDIBELL-Bellvitge Biomedical Research Institute.

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Journal Reference:

Claudia Nieva, Monica Marro, Naiara Santana-Codina, Satish Rao, Dmitri Petrov, Angels Sierra. The Lipid Phenotype of Breast Cancer Cells Characterized by Raman Microspectroscopy: Towards a Stratification of Malignancy. PLoS ONE, 2012; 7 (10): e46456 DOI: 10.1371/journal.pone.0046456

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Blood hormone levels predicted long-term breast cancer risk for postmenopausal women

ScienceDaily (Oct. 18, 2012) — Blood hormone tests predicted a woman's risk for developing postmenopausal breast cancer for up to 20 years, according to data from the Nurses' Health Study presented at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held in Anaheim, Calif., Oct. 16-19, 2012.

"We found that a single hormone level was associated with breast cancer risk for at least 16 to 20 years among postmenopausal women not using postmenopausal hormones," said Xuehong Zhang, M.D., an epidemiologist at Brigham and Women's Hospital and an instructor in medicine at Harvard Medical School in Boston, Mass. "We, and others, are now evaluating if the addition of hormone levels to current risk prediction models can substantially improve our ability to identify high-risk women who would benefit from enhanced screening or chemoprevention. If so, the current data suggest that hormone levels would not need to be measured in the clinic more than once every 10, or possibly 20, years."

Zhang and colleagues analyzed 796 patients with postmenopausal breast cancer who had not received hormone therapy. They conducted blood hormone tests at two time points: between 1989 and 1990, and between 2000 and 2002. They then matched each patient with two controls who were not diagnosed with breast cancer.

Women with hormone levels in the highest 25 percent for estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) had a 50 percent to 107 percent greater chance for developing breast cancer compared with women in the lowest 25 percent. Relative risks for developing breast cancer were similar at one to 10 years versus 11 to 20 years (also 16 to 20 years) after blood collection.

Zhang and colleagues also investigated whether these higher hormone levels were more closely linked to hormone receptor- (HR) positive breast cancers and if they predicted risk regardless of tumor aggressiveness.

In the first case, they found that elevated levels of estradiol increased a woman's risk for HR-positive breast cancer. In general, increased hormone levels, except for DHEAS, tracked closely with increased risk for HR-positive breast cancer. Data on HR-negative cancers were inconclusive.

Elevated hormone levels were also associated with aggressive breast cancer, which the study defined as recurrent or fatal cancer. "The relationship was comparable or possibly stronger for recurrent and fatal breast cancer than it was for overall breast cancer risk, although these results were based on relatively small numbers of participants," said Zhang.

Researchers also confirmed the protective effect of sex hormone-binding globulin (SHBG), which seems to negate the cancer-causing effects of certain hormones. Women in the highest 25 percent of SHBG levels had a 30 percent lower risk for breast cancer compared with women in the lowest 25 percent for SHBG levels.

Zhang noted that the study had low case numbers for several cancer subgroups, including HER2-positive, triple-negative and basal-like breast cancers. More research is necessary to determine the relationship between elevated hormone levels and these important breast cancer subtypes.

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Green Tea and Cancer Prevention: New Clues

By Kathleen Doheny
WebMD Health News

Reviewed by Louise Chang, MD

Oct. 18, 2012 (Anaheim, Calif.) -- Green tea and its extracts have long been studied for health benefits, including cancer prevention.

Now, researchers have new clues about how it may work to help prevent or slow the growth of prostate and breast cancers.

Researchers presented the new findings here today at the American Association for Cancer Research meeting on cancer prevention.

Men with prostate cancer who drank green tea had less prostate tissue inflammation, linked to cancer growth, and other changes than those who didn't drink it, says Susanne M. Henning, PhD, RD, adjunct professor at the David Geffen School of Medicine at the University of California, Los Angeles.

''We were able to show the green tea polyphenols (antioxidants) reached the prostate tissue and they did modify inflammation of the prostate," she says. Polyphenols are antioxidants that protect against cell damage.

Henning's team assigned 79 men with prostate cancer scheduled to undergo surgery to drink either six cups of brewed green tea or water daily. They did so for three to eight weeks, depending on when their surgery was scheduled.

Before and after the study, Henning obtained urine and blood samples. She collected samples of prostate tissue after the surgery.

She reported on the 67 men who finished the study. Levels of prostate-specific antigen, or PSA, were lower after the study in those who drank green teas. Higher levels of PSA, a protein produced by the prostate gland, may reflect prostate cancer.

An indicator of inflammation, called nuclear factor-kappaB, was also reduced in those who drank green tea compared to those who didn't, Henning found. Inflammation is linked to cancer growth.

"We were not able to inhibit tumor growth," she says. But the study length may not have been long enough to show that; a longer-term study is needed, she says.

The National Institutes of Health funded the study.

Prostate cancer is typically a slow-growing cancer, Henning says. That makes it an ideal cancer to try diet interventions to slow it even more.

"Green tea is high in polyphenols and it's convenient," she says.

Other research has found that green tea may slow prostate cancer. An Italian study found that men who had a precursor to prostate cancer and drank green tea were less likely to get prostate cancer, Henning says.

Now, Henning is studying whether adding quercetin, an antioxidant found in apples and onions, to the green tea will ramp up its cancer-fighting ability.

Sumanta Pal, MD, assistant professor of medical oncology at the City of Hope Comprehensive Cancer Center in Duarte, Calif., reviewed the study findings for WebMD.

"Studies such as this are critical to confirm or support a plausible explanation for how green tea may work," he says. More study is needed, however, before making any diet recommendations.

Other researchers reported that an extract from green tea, Polyphenon E, may help inhibit breast cancer by affecting substances called growth factors. Growth factors are involved in the signals that tell breast cancer to grow.

In earlier research, Katherine Crew, MD, assistant professor of medicine and epidemiology at Columbia University Medical Center in New York, had assigned 40 women already treated for breast cancer to take 400, 600, or 800 milligrams of the extract or to take a placebo twice daily for six months.

That was a study to examine any toxic effects of the extract. For the current study, she evaluated blood and urine samples from 34 of the women to see how the extract might work as a cancer fighter.

"We wanted to better understand the biological effects," she says.

"After two months of Polyphenon E, there was a reduction in hepatocyte growth factor," she says. This is one of the growth factors that affect breast cancer cell growth, spread, and invasion. That reduction declined and was not different from the placebo group at four months, however.

It's still too early to recommend green tea extract as a way to prevent breast cancer, Crew says.

The new research on green tea and breast cancer adds to growing evidence of its benefits, according to Joanne Mortimer, MD, director of the Women's Cancer Program at the City of Hope Comprehensive Cancer Center.

"There really does seem to be something there," she says. The new study provides a potential explanation for why green tea may help, she says.

So should women drink green tea with an eye to prevention of breast cancer?

"I don't think we are quite ready to make that leap," Mortimer says. "But it is pretty interesting."

These findings were presented at a medical conference. They should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.

SOURCES: Susanne M. Henning, PhD, RD, adjunct professor, David Geffen School of Medicine, University of California, Los Angeles. Katherine D. Crew, MD, assistant professor of medicine and epidemiology, Columbia University Medical Center, New York. American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research, Oct. 16-19, 2012, Anaheim, Calif. Joanne Mortimer, MD, director of the Women's Cancer Program, City of Hope Comprehensive Cancer Center, Duarte, Calif. Sumanta Pal, MD, assistant professor of medical oncology, City of Hope Comprehensive Cancer Center Duarte, Calif.

©2012 WebMD, LLC. All Rights Reserved.

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Post-Op Radiation May Boost Results for Prostate Cancer Patients: Study

FRIDAY, Oct. 19 (HealthDay News) -- A new French study supports the use of radiation therapy after prostate cancer surgery to help prevent recurrence in high-risk patients.

Surgery to remove the prostate (radical prostatectomy) is one of the main treatments for prostate cancer. Experts, however, say the risk of recurrence can be 10 percent to 50 percent in patients whose cancer has already spread beyond the prostate, so post-surgery radiation therapy is commonly prescribed for these men.

The new study included more than 1,000 high-risk prostate cancer patients who had surgery and were followed for more than 10 years. Some of them had immediate radiation therapy (given within four months of surgery) while others were simply monitored for signs of cancer recurrence (watchful waiting).

After 10 years, 61 percent of men who received immediate radiation therapy remained cancer-free, compared with 38 percent of those in the watchful waiting group, according to the study, which was published online Oct. 18 in the journal The Lancet.

"These long-term results reassure us of the continued benefit and safety of radiation therapy after prostatectomy for a large proportion of men with locally advanced or high-risk prostate cancer," study leader Michel Bolla, a professor at the Centre Hospitalier Universitaire A Michallon, in France, said in a journal news release.

Bolla also noted that factors such as patient age or tumor status could play into decisions around whether to use radiotherapy. Younger patients, or those whose biopsy shows evidence of cancer's spread, may gain from post-surgical radiation treatments, whereas the therapy might cause more harm than benefit for patients aged 70 or older.

Two specialists in the field said the findings come as little surprise.

"This study confirms what radiation oncologists have known for many years -- namely that certain adverse risk factors seen on final [laboratory results] after a prostatectomy warrant immediate postoperative radiation," said Dr. Jonathan Haas, chief of radiation oncology at Winthrop University Hospital in Mineola, N.Y.

Dr. Louis Potters, chairman of radiation medicine at North Shore-LIJ Health System in New Hyde Park, N.Y., agreed.

"In certain men who have surgery for localized prostate cancer, post-operative radiation therapy is a powerful tool that can improve cancer outcomes," he said. Beyond offering certain patients "a second chance at a cure," post-op radiation treatment "also decreases the chances of needing future hormone therapy, which can have an array of unwanted side effects," Potters said.

But Haas stressed that teamwork is key to the proper care of any patient with prostate cancer.

"This study underscores the need for close interdisciplinary cooperation between the urologist, radiation oncologist and pathologist to come up with a tailored treatment plan to maximize outcome for a given patient," he said.

-- Robert Preidt Copyright © 2012 HealthDay. All rights reserved. SOURCES: Jonathan Haas, M.D., chief, radiation oncology, Winthrop University Hospital, Mineola, N.Y.; Louis Potters, M.D., chairman, radiation medicine, North Shore-LIJ Health System, New Hyde Park, N.Y.; The Lancet, news release, Oct. 18, 2012

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Can Allergies Thwart Fatal Colon Cancer?

By Denise Mann
HealthDay Reporter

THURSDAY, Oct. 18 (HealthDay News) -- A new study suggests that people who suffer from both hay fever and asthma may be less likely to die from colon cancer.

The research found that people with both hay fever and asthma were 17 percent less likely to die from colon cancer compared with people who have neither condition. But individuals with hay fever or asthma had little reduction in their risk of fatal colon cancer, according to the report.

People with hay fever and asthma are primed to develop allergic responses, which is why they have hay fever and asthma in the first place. The new theory is that they also mount an allergic response to colon cancer cells, said study author Eric Jacobs, strategic director of pharmacoepidemiology at the American Cancer Society in Atlanta.

"We are trying to understand how the immune system might be helping to slow down or prevent cancer," Jacobs said. "Further research is needed in this area, and if it supports the idea that a naturally occurring immune response can attack some colorectal cancers, vaccines could be developed to treat these cancers."

The study findings were scheduled for presentation Thursday at a cancer prevention meeting of the American Association for Cancer Research in Anaheim, Calif.

To arrive at their findings, the researchers analyzed data from two studies comprising about one million people each. None of the participants in either study had cancer when the studies began, but 19,000 died from colon cancer during the course of the studies.

The American Cancer Society estimates that about 52,000 Americans will die from colorectal cancers this year.

Dr. Andrew Chan, program director of the gastroenterology training program at Massachusetts General Hospital in Boston, said the new study marks an important first step.

"The hope is that we can build on this research and eventually develop a vaccine to treat colon cancer," Chan said. "We need to understand better what it is that is [lowering the risk of dying from] colon cancer," he said. "It's possible that hay fever and asthma are markers of robust immune response."

Chan added that eating a healthy diet and exercising regularly might also help people to prime their immune response and fight cancer.

Nearly 8 percent of U.S. adults have hay fever, according to the American Academy of Allergy, Asthma & Immunology. People with seasonal hay fever are allergic to pollen and spores. Some suffer from hay fever-like symptoms year-round, usually because of an allergy to dust mites, pets, certain chemicals or some foods.

These same allergens can lead to asthma symptoms -- wheezing and cough -- caused by inflammation of the airways.

The data and conclusions of research presented at medical meetings should be considered preliminary until published in a peer-reviewed medical journal.

And, while the study found an association between having hay fever plus asthma and a reduced risk of fatal colon cancer, it did not prove cause-and-effect.

Copyright © 2012 HealthDay. All rights reserved. SOURCES: Eric Jacobs, Ph.D., strategic director, pharmacoepidemiology, American Cancer Society, Atlanta; Andrew Chan, M.D., M.P.H., program director, Gastroenterology Training, Massachusetts General Hospital, Boston; presentation, American Association for Cancer Research, Anaheim, Calif., Oct. 18, 2012

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Depression, DNA Linked to Higher Death Risk in Bladder Cancer Patients

THURSDAY, Oct. 18 (HealthDay News) -- People with significant symptoms of depression and shortened telomeres -- pieces of DNA that protect the ends of chromosomes from deterioration -- are at greater risk of death from bladder cancer, new research suggests.

The findings were scheduled for presentation Wednesday at the annual cancer prevention conference of the American Association for Cancer Research, in Anaheim, Calif.

"We found that patients with bladder cancer with shorter telomeres and high levels of depression symptoms have a threefold increased risk for mortality," Meng Chen, an epidemiologist at the University of Texas MD Anderson Cancer Center, in Houston, said in an association news release.

In conducting the study, the researchers analyzed medical and psychological information on nearly 500 patients with bladder cancer. The participants' level of depression was rated on a standard scale: Patients without symptoms of depression had a score below 16 and those with a score of 16 or greater were considered depressed.

Patients who scored as depressed had an average survival time of 58 months, the study found. In comparison, patients with scores below 16 had an average survival time that exceeded 200 months. Depressed patients had a 1.89 times higher risk of death from all causes than those who were not depressed.

The researchers used patients' blood samples to measure the length of the their telomeres, a marker of aging that is linked to cancer. Patients with depression symptoms and short telomeres had more than a three times higher risk for death and a much shorter period of disease-free survival.

Although the study authors said more research is needed to further investigate their findings, they suggested that psychological factors may play an important role in the survival of people with cancer, along with lifestyle factors that could slow the shortening of telomeres, such as exercise and weight loss.

"In terms of building a prediction model for bladder cancer mortality, current models only focus on clinical variables, such as treatment and tumor stage and grade," Chen said. "Our study suggests that psychological factors and perhaps lifestyle changes could be included in this prediction model."

The study found an association between depression, DNA changes and death after bladder cancer. It did not prove a cause-and-effect relationship. The data and conclusions should be viewed as preliminary until published in a peer-reviewed medical journal.

-- Mary Elizabeth Dallas Copyright © 2012 HealthDay. All rights reserved. SOURCE: American Association for Cancer Research, news release, Oct. 17, 2012

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Blood Test May Help Define Breast Cancer Risk in Older Women

By Barbara Bronson Gray
HealthDay Reporter

THURSDAY, Oct. 18 (HealthDay News) -- The effort to develop a blood test to reveal a woman's risk for breast cancer may be one step closer to fruition, but is still far from becoming a reality, according to a new study.

The researchers found that blood hormone tests may predict the risk for developing postmenopausal breast cancer up to 20 years after a blood sample was taken.

But the study has limitations and needs to be replicated and expanded, said Dr. Xuehong Zhang, lead author and an epidemiologist at Brigham and Women's Hospital in Boston.

If the research is confirmed by other studies, women could have their blood levels of so-called "sex hormones" such as estradiol, testosterone and the androgen DHEAS (dehydroepiandrosterone sulfate) assessed every 10 to 20 years to get a biological assessment of their breast cancer risk, Zhang explained.

"We're thinking that the addition of hormone levels to our current risk prediction models might improve our ability to find high-risk women who would benefit from additional screening or prevention," he said.

The research was scheduled for presentation Thursday at the annual cancer prevention conference of the American Association for Cancer Research (AACR) in Anaheim, Calif.

Although it has been established that levels of estrogen and androgen in the blood can be associated with the risk of postmenopausal breast cancer, researchers haven't known how far into the future that risk prediction might go, Zhang said.

Working with participants in the Nurses' Health Study, a large and long-running effort to study women's health issues, blood samples were collected in 1989 to 1990, and then again in 2000 to 2002. Only postmenopausal women not taking hormones were eligible for this study. The researchers found 796 cases of diagnosed breast cancer through June 2010.

The study showed that women with hormone levels in the top quarter for estradiol, testosterone and DHEAS had a 50 percent to 107 percent greater chance of developing breast cancer as compared to women in the lowest quarter. Elevated hormone levels were also associated with recurrent or fatal breast cancer.

Those women in the highest quarter for sex hormone-binding globulin (SHBG) -- which has been understood to reduce the cancer-causing effects of some hormones -- had a 30 percent lower risk for breast cancer compared to those with SHBG levels in the lowest quarter.

The researchers also found that elevated levels of estrogen increased a woman's risk for hormone receptor-positive breast cancer.

Tests for the levels of these hormones are available now, but the results are often uncertain because laboratories vary greatly in how they define and interpret the results, Zhang said.

A breast cancer expert urged caution in interpreting the study.

"I would ask, if you're postmenopausal and have elevated levels of these hormones, should you potentially turn off your body's hormones [to help prevent breast cancer]?" asked Dr. Julie Gralow, director of breast medical oncology at the Seattle Cancer Care Alliance.

"If the hormones are good for your bones, your heart and maybe the brain, should you do anything to reduce them if you're perceived to be at some increased risk? It could affect your health negatively [to try to reduce those hormone levels]," Gralow said.

Should such a blood test become available, Gralow said she would want women to balance their potential risk of breast cancer against the danger of other diseases and conditions, including osteoporosis and fractures, heart disease and even dementia. "This is an interesting finding that needs to be put into the perspective of the total health of the postmenopausal woman," she said.

Risk factors for breast cancer currently include aging, genetics, race and ethnicity, family history and a personal history of breast cancer, among others, according to the American Cancer Association.

Because this study was presented at a medical meeting, the data and conclusions should be viewed as preliminary until they are published in a peer-reviewed journal.

Copyright © 2012 HealthDay. All rights reserved. SOURCES: Xuehong Zhang, M.D., epidemiologist, Brigham and Women's Hospital, and instructor in medicine, Harvard Medical School, Boston; Julie Gralow, M.D., director, breast medical oncology, Seattle Cancer Care Alliance and professor, medical oncology division, University of Washington School of Medicine, Seattle; Oct. 18, 2012, presentation, American Association for Cancer Research cancer prevention conference, Anaheim, Calif.

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Breast-Feeding Might Cut Risk for Tough-to-Treat Breast Cancer: Study

THURSDAY, Oct. 18 (HealthDay News) -- Breast-feeding may reduce a woman's risk for a form of breast cancer that's particularly difficult to treat, a new study suggests.

The study, by researchers at Columbia University, found that breast-feeding lowered the odds for estrogen receptor-negative and progesterone receptor-negative (ER/PR-) breast cancer.

These types of tumors have cells that do not carry a protein on their surface that binds to the hormones estrogen or progesterone. This means that they cannot be treated with standard hormone-based therapies.

Since there are few modifiable factors for ER/PR-negative breast cancers, the researchers concluded that women at risk for this type of tumor should be encouraged to breast-feed.

The study is scheduled to be presented Thursday at the annual cancer prevention conference of the American Association for Cancer Research (AACR) in Anaheim, Calif.

"We found an increased risk for estrogen receptor- and progesterone receptor-negative breast cancer in women who do not breast-feed, but in women who have children and breast-feed, there is no increased risk," study co-author Meghan Work, a doctoral student in the department of epidemiology at Columbia's Mailman School of Public Health in New York City, said in an AACR news release.

Still, one expert said the findings must be interpreted with caution.

"This was an observational study, and a causal relationship between breast-feeding and the decreased incidence of hormone-negative breast cancer is not established," stressed Dr. Alyssa Gillego, from the department of breast surgical oncology at Beth Israel Comprehensive Cancer Center, in New York City.

The study involved more than 4,000 women with breast cancer and almost 3,000 women without cancer. The researchers used data from the Breast Cancer Family Registry to examine the link between ER/PR-negative breast cancer and women's reproductive risk factors, such as the number of children they delivered and whether or not they breast-fed or took oral contraceptives.

The study found that having three or more children but not breast-feeding was linked to an increased risk ER/PR-negative breast cancer.

"Women who had children but did not breast-feed had about 1.5 times the risk for ER/PR-negative breast cancer when compared with a control population. If women breast-fed their children, there was no increased risk for ER/PR-negative cancer," Work noted. "This is particularly important as breast-feeding is a modifiable factor that can be promoted and supported through health policy."

They study also revealed that use of oral contraceptives made after 1975 was not associated with an increased risk for ER/PR-negative cancer risk.

Another specialist added, however, that there is a plausible explanation for a connection between breast-feeding and breast-cancer.

"Obviously, the breasts are meant to serve as an organ that produces milk for a newborn," explained Dr. Stephanie Bernik, chief of surgical oncology at Lenox Hill Hospital, in New York City. "Breasts are in an immature state until one's first pregnancy. Theoretically, if left in the immature state, breasts are not developing in the manner that nature intended. This altering of what nature intended may be the reason why women that do not breast-feed have a higher rate of cancer."

There could be other factors, she added. "The lowered risk might also be due to exposure or withdrawal of hormones as one nurses an infant," Bernik reasoned. "More study needs to be directed to finding out why nursing is protective, as this might lead to new methods of preventing breast cancer development."

Findings presented at medical meetings are typically considered preliminary until published in a peer-reviewed journal.

-- Mary Elizabeth Dallas Copyright © 2012 HealthDay. All rights reserved. SOURCES: Alyssa Gillego, M.D., department of breast surgical oncology, Beth Israel Comprehensive Cancer Center, New York City; Stephanie Bernik, M.D,, chief of surgical oncology, Lenox Hill Hospital, New York City; American Association for Cancer Research, news release, Oct. 18, 2012

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Plant-based foods may offer reduced risk for aggressive prostate cancer

ScienceDaily (Oct. 19, 2012) — President George W. Bush made no secret that he detested broccoli. With all due respect to our former leader, researchers have found one more great reason to add fruits, vegetables, herbs and tea to your diet.

A study by Susan Steck of the Arnold School of Public Health finds that a high intake of flavonoids, a group of compounds found in plants, may lower the risk for highly aggressive prostate cancer.

"Incorporating more plant-based foods and beverages, such as fruits, vegetables, herbs and tea, into the diet may offer some protection against aggressive prostate cancer," said Steck, an associate professor at the Arnold School and an affiliated scholar with the Center for Research in Health Disparities.

"Filling your plate with flavonoid-rich foods is one behavior that can be changed to have a beneficial impact on health," she said.

Steck presented her findings at the International Conference on Frontiers in Cancer Prevention Research. The annual event is sponsored by the American Association for Cancer Research, whose mission is to prevent and cure cancer through research, education, communication and collaboration.

Prior preclinical studies have shown that flavonoids have beneficial effects against prostate cancer, but few studies have examined the effect of flavonoids on prostate cancer in humans.

Steck and her colleagues used data from 920 African-American men and 977 white men in the North Carolina-Louisiana Prostate Cancer Project who were newly diagnosed with prostate cancer. Participants completed a self-reported dietary history questionnaire to assess flavonoid intake, which was measured using the U.S. Department of Agriculture's 2011 Database for the Flavonoid Content of Selected Foods.

Men with the highest total intake of flavonoids had a 25 percent lower risk for aggressive prostate cancer compared with those men with the lowest flavonoid intake.

"We found that higher total flavonoid intake was associated with reduced odds for aggressive prostate cancer in both African-American and European-American men, but no individual subclass of flavonoids appeared to be protective independently, suggesting that it is important to consume a variety of plant-based foods in the diet, rather than to focus on one specific type of flavonoid or flavonoid-rich food," Steck said.

In addition, the risk for aggressive prostate cancer was even lower in those men younger than 65 and in current smokers with the highest levels of flavonoid intake. Dietary questionnaire results revealed that citrus fruits and juices, such as oranges and grapefruits, tea, grapes, strawberries, onions and cooked greens were the top contributors to total flavonoid intake among the participants. "The results support public health recommendations and guidelines from organizations such as the American Institute for Cancer Research to consume a more plant-based diet," Steck said. "In particular, consuming more flavonoid-rich foods may be beneficial for those people who are at increased risk for cancer, such as smokers."

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New insights into how genetic differences influence breast cancer risk from low-dose radiation

ScienceDaily (Oct. 16, 2012) — Scientists from the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) have identified tissue mechanisms that may influence a woman's susceptibility or resistance to breast cancer after exposure to low-dose ionizing radiation, such as the levels used in full-body CT scans and radiotherapy.

The research could lead to new ways to identify women who have higher or lower risks of breast cancer from low-dose radiation. Such a predictive tool could help guide the treatment of cancer patients who may be better served by non-radiation therapies.

The findings also support the idea that a person's genes play a big role in determining her risk of breast cancer from low-dose radiation. The current model for predicting cancer risk from ionizing radiation holds that risk is directly proportional to dose. But there's a growing understanding that this linear relationship doesn't apply at lower doses. Instead, the health effects of low-dose radiation may vary substantially among people depending on their genetic makeup.

The scientists, led by Andy Wyrobek of Berkeley Lab's Life Sciences Division, report their research October 15 in the journal PLOS ONE.

They studied mammary tissue from two strains of mice -- one that is susceptible to radiation-induced mammary gland cancer and one that is resistant -- before and after the mice were exposed to low-dose radiation.

The team then looked for differences between the two strains in how their genes turn on and off. They used a method that scans thousands of genes simultaneously. They found differences in genes that regulate tissue stress response, DNA repair, immune response, cellular proliferation, and other cellular and tissue mechanisms.

They also found that these differences carried over to breast cancer survivability in women. Breast cancer patients with gene expression profiles like the cancer-resistant mice (before radiation exposure) were more likely to survive eight years after diagnosis. Women with gene expression profiles like the cancer-sensitive mice were less likely to survive after eight years.

Based on this, the scientists believe the cellular and tissue mechanisms that control mice's risk of mammary gland cancer from low-dose radiation are similar to the mechanisms that affect a woman's chance of surviving breast cancer.

"Our studies of genetic differences in radiation sensitivity in mice, and individual variation in breast cancer survival in women, suggest that there are women who, because of their genes, have a higher risk of breast cancer when they're exposed to low-dose radiation," says Andy Wyrobek, who conducted the research with Antoine Snijders, Joe Gray, and several other Berkeley Lab scientists.

"This raises the possibility that we can use gene expression profiles to develop simple tests that screen for women who may be sensitive to low-dose radiation versus women who are resistant," Snijders says.

The scientists first studied mice before radiation exposure. They found more than 130 genes that express differently in blood and mammary tissue samples of cancer-resistant mice compared to cancer-sensitive mice.

To determine if these differences also apply to people, the scientists mined human breast cancer "knowledge bases" that link the expression of patients' tumor genes with their survival outcomes. They studied newly diagnosed women before they received radiation or chemical therapies. Women with gene expression levels like those of radiation-sensitive mice were less likely to survive after eight years. In contrast, women with expression levels like those of the resistant strain were more likely to survive the eight-year duration of the follow-up.

Next, gene expression analyses conducted a few hours after the end of low-dose exposure found changes in many genes in the mammary tissue of cancer-sensitive mice. Large numbers of genes that regulate their immune system were suppressed, while genes that regulate pubertal mammary gland development were turned on in error. In cancer-resistant mice, these genes showed only a small change in activity.

Analyses conducted one month after exposure yielded striking differences in the expression of a large set of genes that control cell proliferation. The cancer-sensitive mice had up-regulated many genes associated with cell division and cell renewal. The cancer-resistant mice had down-regulated these same genes below normal levels, which suggests they were able to activate tissue mechanisms that prevent cellular proliferation that can lead to cancer.

These differences again carried over to people. Breast cancer patients whose cell division and renewal genes were up-regulated like the cancer-sensitive mice didn't survive as long as patients in which the same genes were suppressed.

The scientists are now refining these gene expression signatures by studying large groups of women with breast cancer. They're also testing the mechanisms by which these signatures control radiation sensitivity using special breast cell culture models developed at Berkeley Lab.

"This research opens promising opportunities for developing blood tests that predict a woman's risk for breast cancer, and which identify women who are susceptible to the cancer effects of low-dose radiation exposures," says Wyrobek.

This research was supported by Berkeley Lab's Laboratory Directed Research and Development fund and the Department of Energy's Office of Science.

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Journal Reference:

Antoine M. Snijders, Francesco Marchetti, Sandhya Bhatnagar, Nadire Duru, Ju Han, Zhi Hu, Jian-Hua Mao, Joe W. Gray, Andrew J. Wyrobek. Genetic Differences in Transcript Responses to Low-Dose Ionizing Radiation Identify Tissue Functions Associated with Breast Cancer Susceptibility. PLoS ONE, 2012; 7 (10): e45394 DOI: 10.1371/journal.pone.0045394

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Increased flavonoid intake reduced risk for aggressive prostate cancer

ScienceDaily (Oct. 17, 2012) — A high total intake of flavonoids, a group of compounds found in plants, was inversely associated with the risk for highly aggressive prostate cancer, according to data presented at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held in Anaheim, Calif. Oct. 16-19, 2012.

"Incorporating more plant-based foods and beverages, such as fruits, vegetables, herbs and tea, into the diet may offer some protection against aggressive prostate cancer," said Susan E. Steck, Ph.D., M.P.H, R.D., associate professor at the Arnold School of Public Health at the University of South Carolina. "Filling your plate with flavonoid-rich foods is one behavior that can be changed to have a beneficial impact on health."

Prior preclinical studies have shown that flavonoids have beneficial effects against prostate cancer, but few studies have examined the effect of flavonoids on prostate cancer in humans.

Steck and her colleagues used data from 920 African-American men and 977 European-American men in the North Carolina-Louisiana Prostate Cancer Project who were newly diagnosed with prostate cancer. Participants completed a self-reported dietary history questionnaire to assess flavonoid intake, which was measured using the U.S. Department of Agriculture's 2011 Database for the Flavonoid Content of Selected Foods.

Men with the highest total intake of flavonoids had a 25 percent lower risk for aggressive prostate cancer compared with those men with the lowest flavonoid intake.

"We found that higher total flavonoid intake was associated with reduced odds for aggressive prostate cancer in both African-American and European-American men, but no individual subclass of flavonoids appeared to be protective independently, suggesting that it is important to consume a variety of plant-based foods in the diet, rather than to focus on one specific type of flavonoid or flavonoid-rich food," Steck said.

In addition, the risk for aggressive prostate cancer was even lower in those men younger than 65 and in current smokers with the highest levels of flavonoid intake. Dietary questionnaire results revealed that citrus fruits and juices, such as oranges and grapefruits, tea, grapes, strawberries, onions and cooked greens were the top contributors to total flavonoid intake among the participants.

"The results support public health recommendations and guidelines from organizations such as the American Institute for Cancer Research to consume a more plant-based diet," Steck said. "In particular, consuming more flavonoid-rich foods may be beneficial for those people who are at increased risk for cancer, such as smokers."

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Targeted Radiation Therapy Minimizes GI Side Effects for Prostate Cancer Patients, Penn Study Shows

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Daily multivitamin use reduced cancer occurrence in men

ScienceDaily (Oct. 17, 2012) — Daily use of a common multivitamin reduced the risk for total cancer occurrence in a population of men followed for more than a decade, according to new data from the Physicians' Health Study II presented at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held here Oct. 16-19, 2012.

The study is being simultaneously published in the Journal of the American Medical Association.

"More than half of Americans take some kind of vitamin supplement, and the most commonly taken is a multivitamin," said John Michael Gaziano, M.D., chief of the Division of Aging at Brigham and Women's Hospital and a researcher at VA Boston. "No one has ever done a long-term trial to determine the potential health benefits or downsides of taking a multivitamin for a long period of time."

Gaziano and colleagues investigated the long-term effects of daily multivitamin use on certain site-specific cancers and total cancer occurrence and mortality. They used data from the Physicians' Health Study II, which included 14,641 male physicians aged 50 or older from the United States.

Researchers randomly assigned participants to a multivitamin or no multivitamin between 1997 and June 2011. During the median follow-up of 11.2 years, researchers recorded 2,669 cancer cases, including 1,373 prostate cancer cases and 210 colorectal cancer cases.

When examining outcomes at the study's end, the researchers found an 8 percent reduction in total cancer occurrence among participants assigned to multivitamin use.

"We also saw trends for some of the major site-specific cancers, though the numbers were small and not significant," Gaziano said. "There also seemed to be a greater effect in people with previous cancer."

Although prostate cancer was the most commonly occurring cancer in this population, there was no direct effect of multivitamin use on prostate cancer occurrence. However, when the researchers looked at the effect of a multivitamin on other site-specific cancers, they found about a 12 percent reduction in occurrence, according to Gaziano. Additionally, they saw a nonsignificant 12 percent reduction in cancer mortality.

"There are reasons to take a multivitamin even in our adult population, who are seemingly well nourished, as a way to get recommended daily amounts of vitamins and minerals," Gaziano said. "This study suggests, at least for men, that there might be benefits to taking multivitamins in terms of cancer as well."

Gaziano emphasized that the effects were modest and that multivitamin use should only be considered in addition to other habits, such as stopping smoking and increasing exercising, which literature has shown are effective in preventing cancer and other diseases.

Gaziano and colleagues plan to follow this population to determine if this effect strengthens over time. In addition, more studies on multivitamin use are needed in women.

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Gaziano J, Sesso HD, Christen WG, et al. Multivitamins in the Prevention of Cancer in Men: The Physicians' Health Study II Randomized Controlled Trial. JAMA, 2012; DOI: 10.1001/jama.2012.14641

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