Not only did the U.S. Preventive Services Task Force (USPSTF) just raise the age at which it recommends women get their first mammogram from 40 to 50, but the American College of Obstetrics and Gynecologists (ACOG) decided that adolescents should be spared the inconvenience and possible risks of cervical cancer screening, and wait until they reach the age of 21 for such testing. Both groups also recommended screening less frequently.

Add to that the long-simmering debate on the value of PSA testing for prostate cancer and the fact that both the American Cancer Society (ACS) and the American College of Radiology have condemned the new USPSTF recommendations, it’s no wonder patients and even experts feel like they are suffering from a bad case of medical whiplash.

Was the timing of the announcements anything more than coincidence? Are the changes a reflection of new science, attempts to influence the current raging health-care debate or just medical business as usual?

The timing, by most accounts, was purely accidental.

“I think it’s a coincidence that this [the mammogram recommendation] came out when it did, right in the middle of the health-care reform discussion. It’s a good panel, one that was dedicated to getting the right answer to what should be done about this,” said Dr. Robert J. Barnet, senior scholar in residence at the Center for Clinical Bioethics at Georgetown University, in Washington, D.C.

Added Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La: “This is nothing new. Cancer screening guidelines have been changing as more scientific knowledge accumulates.”

And much of the new knowledge does suggest that over-screening does happen, often resulting in false-positive results, which lead to more biopsies and more angst. This is true of breast, cervical, prostate and other forms of cancer, experts concur.

“There’s appropriate screening and there is the appropriate population that should be getting that screening, and there is the appropriate screening interval,” said Dr. Otis Brawley, chief medical officer of the American Cancer Society. “We can violate all of those things.”

Meanwhile, false-positive results from mammographies are more common in younger (age 40 to 49) women than in the upper age bracket. And the age cut-offs for screening may be artificial.

“We like to lump people into big decades of life, so the risk of a 40-year-old woman and the risk of a 49-year-old woman [for breast cancer] are different,” Brooks noted. “The risk at 40 is much less than the risk at 49.”

“Younger women are at higher rates of false-positives, which results in more biopsies, more procedures being done and women getting callbacks for extra mammograms,” he added. “This creates anxiety for something that’s not anything bad.”

Also, there’s increasing evidence that some cancers will never turn into anything dangerous and, therefore, don’t warrant treatment.

“Our definition of cancer was given to us by German pathologists in the 1840s after they looked at biopsies from autopsy specimens,” Brawley explained. “Now, 170 years later, we’ve progressed in terms of imaging, in terms of medical diagnostics into what I call the genetic and molecular biologic age, but our ability to define cancer has not progressed beyond the light microscope. What we need to be able to do eventually is say that ‘this cancer is never going to progress,’ it is not going to spread and invade other organs in the body. But right now we don’t have the molecular tools to predict their behavior.”

“Not only do we need to find small tumors, we need to know more about the biology of those tumors,” added Dr. Michael V. Seiden, president and CEO of Fox Chase Cancer Center in Philadelphia.

Until those tools are developed, imperfect screening is going to lead to over-diagnosis and unnecessary treatment.

Still, there’s no question that the revisions do fit into a larger and rapidly changing health-care picture.

“Where I think the question was solely focused on ‘can you prevent cancer death?’ … 10 years ago or 20 years ago, I think there has been a much more open dialogue about the burden of screening, the cost burden, the anxiety burden, the false-positive burden,” Seiden said. “As screening techniques become more sensitive, you do a better and better job of capturing people with cancer but you also do a better job of capturing people with tumors they might not have died from. So, all of a sudden the incidence of pre-malignant breast disease, the incidence of low-grade prostate cancer, starts doubling and the death rate drops, but only very, very modestly.”

While the USPSTF stated that cost considerations had nothing to do with the new breast cancer recommendations announcement, ACOG did mention costs in its announcement regarding changes to cervical cancer screening.

“In this country, health care is an enormous issue and it is the single greatest driver of the national debt,” Brooks said. “There’s nothing wrong with raising financial questions in a public health setting.”

“It’s my belief that the task force just set the date [for its announcement] and wasn’t really paying attention to the politics. In truth, I don’t know but . . . part of the way of controlling costs is the rational use of medical care, not the rationing of care,” Brawley said. “For most women in the U.S., to get a Pap smear on an annual basis means that we’re going to spend three times more on cervical cancer screening than we need to spend and we’ve actually gotten evidence that screening tests every five years is going to save as many women as every three years [but] we’ve gone every three years to be safer.”

According to Brawley, ACOG’s new cervical cancer guidelines “look amazingly” like the 2002 American Cancer Society guidelines.

The ACS does not agree with the new USPSTF guidelines for breast cancer screening, however.

“Our view is that breast cancer screening saves lives and women aged 40 and above should get a high quality mammogram and clinical breast exam on an annual basis,” Brawley said.

Ochsner Health System’s Brooks is not changing his advice to women. “I tell women at age 40, if she wants to begin screening with mammography, it’s fine,” he said. “I haven’t changed what I’m recommending in my practice but I try to explain to women what the rationale behind it is.”

Researchers followed 12,152 American and European male and female smokers, formers smokers and nonsmokers for three years. During that time, current smokers were 4.16 times more likely to die of cancer, 2.26 times more likely to die of heart disease and 2.58 times more likely to die from any cause than were former or nonsmokers. Current smokers were also more likely to suffer a heart attack or stroke.

There were no significant differences between former smokers and nonsmokers in the risk for dying from heart disease or any cause, but former smokers were more likely to die of cancer than those who’d never smoked.

“The analysis provides further strong evidence that people with heart disease who continue to smoke take a very high risk of increasing their chances of death in the short term,” principal investigator Dr. Deepak L. Bhatt, chief of cardiology at the Veterans Affairs Boston Healthcare System, said in a news release from the American Heart Association.

“This study provides impetus for a smoker to stop,” he said. “The benefits of risk reduction accrue relatively quickly when someone stops smoking, although the lingering cancer risk is still there.”

Researchers followed 12,152 American and European male and female smokers, formers smokers and nonsmokers for three years. During that time, current smokers were 4.16 times more likely to die of cancer, 2.26 times more likely to die of heart disease and 2.58 times more likely to die from any cause than were former or nonsmokers. Current smokers were also more likely to suffer a heart attack or stroke.

There were no significant differences between former smokers and nonsmokers in the risk for dying from heart disease or any cause, but former smokers were more likely to die of cancer than those who’d never smoked.

“The analysis provides further strong evidence that people with heart disease who continue to smoke take a very high risk of increasing their chances of death in the short term,” principal investigator Dr. Deepak L. Bhatt, chief of cardiology at the Veterans Affairs Boston Healthcare System, said in a news release from the American Heart Association.

“This study provides impetus for a smoker to stop,” he said. “The benefits of risk reduction accrue relatively quickly when someone stops smoking, although the lingering cancer risk is still there.”

Men who consistently failed to express their resentment over conflicts with a fellow worker or supervisor were more than twice as likely to have a heart attack or die of heart disease as those who vented their anger, claims a report in the Nov. 24 online edition of the Journal of Epidemiology and Community Health.

In fact, ignoring an ongoing work-related conflict was associated with a tripled risk of heart attack or coronary death, the study of almost 2,800 Swedish working men found.

“It is not good just to walk away after having such a conflict or to swallow one’s feelings,” said study co-author Constanze Leineweber, a psychologist at Stockholm University’s Stress Research Institute.

The study did not specify good ways of coping with work-related stress — “We just looked at the bad side of coping,” Leineweber explained.

The study doesn’t advocate being belligerent at work, Leineweber cautioned. “Shouting out, and so on, is not proper coping,” she said.

But venting one’s anger outside of the workplace didn’t seem to take a cardiovascular toll, at least. “Getting into a bad temper at home” was not associated with an increased risk of heart attack or cardiac death, the study authors found.

The findings echo those from a study published last year in the journal Occupational and Environmental Medicine. That study, also from Sweden and involving more than 3,100 men, found that having an overbearing or incompetent boss boosted workers’ odds for angina, heart attack and death.

Leineweber stressed that what is true for men might not be true for female workers. While the study included more than 2,000 women, too few of them had heart attacks or died of heart disease to allow conclusions to be drawn.

“Earlier studies have indicated that women use different coping strategies than men,” Leinewaber said. “So for women, strategies such as going away and not saying anything might not be good.”

Women in general appear to handle stressful situations better than men, noted Dr. Bruce S. Rabin, director of the Healthy Lifestyle Program at the University of Pittsburgh Medical Center.

“Social interaction, having people to talk to, is extremely important,” Rabin said. “If you keep things to yourself, you have high levels of stress hormones. Women are more comfortable in social interactions than men. They talk more, while men tend to keep within themselves.”

A study, conducted by the Swedish researchers in 2005, found that women did not have the same levels of cardiovascular risk factors as men, Rabin noted.

There is no one key to handling on-the-job stress, because the level of stress depends on an individual’s environment, at work and in the home, he said.

“Work environment is important,” Rabin said. “You need interaction between people so that everybody feels they can express their opinions about their work. You shouldn’t come to work with a feeling that no one cares.”

“And when you go home, it is very important to share your feelings with whomever you are sharing with,” Rabin added. “Also, you should understand that children learn from the behavior of parents. You can have a meaningful effect on the long-term health of children by being good role models. The message is that the environment you culture can affect not only your health but also the health of those who are important to you.”

The study from the Massachusetts General Hospital Cancer Center in Boston found that survival and tumor response in patients treated with bevacizumab (Avastin), an angiogenesis inhibitor that has helped slow the growth of other cancers, in addition to the chemotherapy regimen of gemcitabine and oxaliplatin — a combined treatment called GEMOX-B — was comparable to findings in previous studies in which patients were treated with gemcitabine and oxaliplatin alone.

In the new phase 2 trial, 35 biliary-tract cancer patients were given all three drugs intravenously (bevacizumab at 10 milligrams per kilogram, followed by gemcitabine at 1,000 milligrams per square meter, and oxaliplatin at 85 milligrams per square meter) on days 1 and 15, every 28 days. Whole-body PET scans were used to assess patients at the start of the study and at the end of the second cycle of treatment.

The researchers found that the overall tumor response rate was 40 percent (14 patients with confirmed partial responses) and stable disease was noted in another 10 patients (29 percent). The overall survival was found to be 12.7 months, with a median progression-free survival of seven months. However, progression-free survival at six months was below the targeted rate at 63 percent, they noted.

The most common negative side effects of GEMOX-B therapy were fatigue, an abnormally low number of white blood cells, peripheral neuropathy, high blood pressure and gastrointestinal problems, but the therapy was generally well-tolerated, the study authors pointed out.

The findings add to increasing evidence “supporting the combination of molecularly targeted agents with chemotherapy to further improve treatment outcomes in patients with biliary-tract cancers,” the researchers wrote.

In 1981, Dr. Brian J. McMahon, from the Alaska Native Medical Center, Anchorage, and his colleagues gave more than 1500 Alaska Native adults and children over age 6 months three doses of hepatitis B vaccine. Before the hepatitis B vaccine was licensed for U.S. use in 1981, as many as one in 12 Alaskan Natives were infected.

In 2003, the team checked with almost 500 of those given the shots and had a response to them at the time to see who was still showing evidence of an immune system response. Blood tests found that more than half – 60 percent — were still considered immune to the virus.

To test whether the other 40 percent were immune, they were given a booster dose of the vaccine, to simulate infection. Most of those people – more than 80 percent – showed a response.

Overall, the researchers estimate that more than 90 percent of the original group was protected. There were no long-term hepatitis B infections in the group, which also suggests a high level of protection, they note in a report in the Journal of Infectious Diseases.

They conclude, “in light of the strong evidence we present here, hepatitis B vaccine booster doses are not currently indicated.”

More than other methods, including antidepressants, this combination best mimics the actual highs and lows of smoking to help smokers kick their habit, experts said.

“The study shows that, yes, one therapy came out on top, the patch and the lozenge [together],” said Dr. Jonathan H. Whiteson, co-director of the Joan and Joel Smilow Cardiopulmonary Rehabilitation and Prevention Center at NYU Langone Medical Center in New York City.

“The reasoning behind it is that the patch supplies a steady supply of nicotine replacement and the lozenges give a boost of nicotine which you can use when you have an extra craving. It gives people control,” said Whiteson, who was not involved in the research.

“If you combine these different types of nicotine replacement you’re going to get the best bang for your buck,” added Megan E. Piper, lead author of the new study and an assistant professor at the Center for Tobacco Research and Intervention at the University of Wisconsin, Madison. “But also remember that in this study people got a lot of counseling. It was that combination that resulted in a 40 percent quit rate [at six months out].”

In fact, coupling the patch with the lozenge was the only intervention that performed better than a placebo, reported the study, which appears in the November issue of the Archives of General Psychiatry.

The study adds insight to a field that’s long suffered from too little research. “As each medication comes out, it is tested against a placebo,” but not against other methods, Piper explained. “There just hasn’t been the funding or the availability of a program to do something like that.”

This research was funded by the U.S. National Institutes of Health. Medication was provided free by drug maker GlaxoSmithKline. Several of the study authors reported financial ties to different pharmaceutical companies.

For this study, 1,504 adults who had smoked at least half a pack a day for the past six months and wanted to quit were randomly assigned to a placebo or one of five different quit-smoking interventions: nicotine lozenge, nicotine patch, bupropion (Wellbutrin, an antidepressant), nicotine patch plus nicotine lozenge, and bupropion plus nicotine lozenge. All groups received six individual counseling sessions with a case manager.

The nicotine patch, which has been available for more than two decades, is currently the most widely used pharmacotherapy to help people quit smoking.

However, only the combination of the nicotine patch and the lozenge performed significantly better than placebo six months after the person smoked their last cigarette, the team found.

People taking the patch-lozenge combination were also more likely to have sworn off cigarettes after one week and were more likely to have attained one full day without smoking, the researchers said.

The 40 percent (at six months) success rate reported here will decline as time goes on, Whiteson noted. He added, however, that in the smoking cessation arena, “even the 30 percent range is very good.”

Another expert said the study raised some key concerns. “The question is, how many of them had to continue on the lozenge in order to stay off cigarettes? I always tell people not to do the lozenge alone because it mimics the very thing that smoking does, which gives you a spike. Then, when you reach a trough, you pick up a lozenge — or cigarette,” said Dr. Len Horovitz, a pulmonary specialist with Lenox Hill Hospital in New York City. “Once they stopped everything, could they do without the spikes and troughs [of the lozenge], which mimics physiologically everything the cigarette is doing? Smoking is a two-pronged problem. There’s nicotine dependence and a behavioral aspect to it.”

Dr. Elliot Wineburg, assistant clinical professor of psychiatry at Mount Sinai School of Medicine in New York City, felt the study suffered from some limitations, namely lack of individual attention to individual smokers’ habits.

“The authors said that they gave the patients lozenges according to the company’s [instructions],” he said. But this doesn’t take into account how much people smoke or how strong their cigarettes are. “They don’t even look into the amount of nicotine a person takes.”

The National Institute on Aging (NIA), part of the National Institutes of Health, today announced the start of a large-scale clinical trial to evaluate the effect of testosterone therapy on older men. Led by the University of Pennsylvania School of Medicine and conducted at 12 sites across the nation, the Testosterone Trial will involve 800 men age 65 and older with low testosterone levels.

“We know that, as men get older, a significant proportion are unable to carry out activities of daily living and experience decreased physical and cognitive function and decreased independence,” said NIA Director Richard J. Hodes, M.D. “We do not know the extent to which low levels of testosterone may contribute to these conditions.”

A 2004 report by the Institute of Medicine, “Testosterone and Aging: Clinical Research Directions,” noted several important unanswered questions about the effects of testosterone therapy. The NIA is aiming to answer these questions by testing the effectiveness of testosterone therapy in older men with low testosterone levels and one of the following conditions: impaired walking, low vitality, sexual or cognitive dysfunction. A key consideration is the use of testosterone as a therapy for certain conditions, rather than as a preventive measure.

The NIA is the primary source of support for this trial. Additional funding is being provided by the National Heart, Lung, and Blood Institute (NHLBI); the National Institute on Neurological Disorders and Stroke (NINDS); the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Solvay Pharmaceuticals, which is also supplying the study drug.

The Testosterone Trial will include five separate studies. At each of the 12 sites, men 65 and older with low serum testosterone and at least one of the following conditions — anemia, decreased physical function, low vitality, impaired cognition or reduced sexual function — will be randomly assigned to participate in a treatment group or a control group. Treatment groups will be given a testosterone gel that is applied to the torso, abdomen, or upper arms; control groups will receive a placebo gel. Serum testosterone will be measured monthly for the first three months and quarterly thereafter up to one year. Participants will be tested on a wide range of measures to evaluate physical function, vitality, cognition, cardiovascular disease, and sexual function.

“This study is important because testosterone products have been marketed for many years as treatments for a variety of conditions,” said Evan C. Hadley, M.D., director of NIA’s Division of Geriatrics and Clinical Gerontology, which is the primary funder of the trial. “”We hope this trial will establish whether testosterone therapy results in clear benefits for older men.”

The University of Pennsylvania School of Medicine is the lead institution for the trial and will serve as coordinating center for the study sites. Peter J. Snyder, M.D., professor of medicine in the Division of Endocrinology, Diabetes and Metabolism at Penn, is the principal investigator and will oversee trial activities. “This is an unprecedented opportunity for older men to learn more about themselves and at the same time help find out if testosterone will improve some of the afflictions of old age,” said Dr. Snyder.

Recruitment of study participants will begin in November of 2009. Men age 65 and older who are interested in participating should call the site closest to them. Men living within a 50-mile radius of the study centers, listed below, are especially encouraged to participate.

Participating institutions and their phone numbers include:
University of California, Los Angeles; 310-222-5297
University of California, San Diego; 877-219-6610
Boston University; 617-414-2968
University of Pittsburgh; 800-872-3653
Albert Einstein College of Medicine, Bronx, N.Y.; 718-405-8271
Baylor College of Medicine, Houston, Texas; 713-798-8343
University of Minnesota, Minneapolis; 612-625-4449
Yale University, New Haven, Conn.; 203-737-5672
University of Alabama at Birmingham; 205-934-2294
VA Puget Sound Health Care System and University of Washington School of Medicine, Seattle; 206-768-5408
Northwestern University, Evanston, Ill.; 877-300-3065
University of Florida, Gainesville; 866-386-7730, 352-273-5919

In a paper to be presented Monday at the American Society for Radiation Oncology annual meeting in Chicago, lead researcher Dr. Bryan Burmeister, a radiation oncologist at Princess Alexandra Hospital in Brisbane, reported the hopeful findings from the five-year study.

“Results of this trial now confirm the place of radiation therapy in the management of patients who have high-risk features following surgery for melanoma involving the lymph nodes,” Burmeister said in a news release. “In some institutions, radiation treatment is routine protocol, while in others, the protocol has been either for patients to just be observed or receive some type of adjuvant chemotherapy or immunotherapy. I encourage patients with melanoma to talk to their doctors about whether radiation should be added to their treatment plan.”

External beam radiation involves the use of a beam (or beams) of radiation directed through the skin to the cancer and the tissue in its immediate vicinity. This targeted radiation destroys the tumor while helping to mop up nearby cancer cells that might remain after surgery. The therapy is usually painless and performed on an outpatient basis.

Burmeister’s study followed 217 patients with melanoma, a deadly skin cancer, between 2002 and 2007. All had at least one lymph node removed after doctors determined that the cancer had spread into the nodes. The surgery, called a lymphadenectomy, is standard treatment for metastasized melanoma.

About half the patients underwent postoperative radiation treatment, while the other half followed-up with their physicians to see if their cancer had returned. By the end of the study, 19 percent of the radiation patients had experienced a local nodal relapse of their melanoma, compared with 31 percent of patients who did not undergo postoperative radiation treatment. Overall survival was not affected, however.

Melanoma starts in the melanocytes, which are cells found in the top layer of skin that are responsible for producing the pigment melanin. Melanoma can arise anywhere there is pigmented tissue, including the eyes, sinuses, anus and a woman’s vulva.

According to the Memorial Sloan-Kettering Cancer Center in New York City, skin melanomas often look asymmetrical, have a ragged or blurred border and are dark in color. But rare forms of melanoma contain no pigment and can appear as pink nodules on the skin.

The disease is less common than other skin cancers, but if untreated, melanoma can spread and be difficult to cure. In the United States, more than 67,000 people annually are diagnosed with melanoma, and more than 8,000 will die, according to the American Cancer Society.

Given the severity of the disease, U.S. melanoma experts said they found the study intriguing.

“This is the first randomized study that tested the question whether postoperative radiation therapy offered any advantage in terms of loco-regional control to patients with loco-regionally advanced melanoma,” said Dr. Nancy Lee, a radiation oncologist at Memorial Sloan-Kettering. “The authors are to be congratulated for finally completing an important study in our field. This is particularly important as [local] recurrence can be devastating and often is difficult to salvage with additional therapy.”

Dr. David Fisher, of Boston’s Massachusetts General Hospital, praised the study but said he wanted more data on overall survival.

“This is an important study, since decisive data on the value of adjuvant radiation therapy have been lacking,” said Fisher, director of the melanoma program at Mass General. “It will be important to learn additional details, but the study appears to provide important supportive evidence for adjuvant radiation therapy.”

Social isolation can actually change the expression of genes important in the growth of mammary gland tumors, according to Dr. Suzanne D. Conzen, an associate professor of medicine at the University of Chicago and the study’s lead author.

“As far as we know, this is the first assessment of gene expression in mammary glands, looking at the molecular basis for differences in tumor development under the setting of social stress,” Conzen said at a news conference Tuesday.

The findings, published in the October issue of Cancer Prevention Research, follow other studies, some in humans, that showed stress can adversely impact cancer. One study, for instance, found that stressful marriages are bad for breast cancer recovery.

Conzen and her colleagues randomly assigned mice that were genetically susceptible to breast cancer to live either in isolation or in group housing.

“We separated the mice at a very young age, just a few days after they had been weaned from their mothers’ milk,” Conzen said. “Mice are social animals. In the wild, they live in groups of three or four. They have dramatic responses to isolation.”

“What we found was the isolated mice developed larger and more breast cancers than the group-housed mice,” she added.

Three and a half weeks into the isolation, Conzen’s team measured gene expression in the animals’ mammary glands, the equivalent of the human breast. “We found very reproducible changes in gene expression [in the isolated mice]. We found genes that were turned on and turned off that had to do with metabolism,” she said. These pathways are known to contribute to increased growth of breast cancer, she added.

The isolated mice also had a higher corticosterone stress hormone response than did the group-housed mice.

The changes in the expression levels of metabolic pathway genes occurred in the isolated mice even before the tumor size differences were able to be measured, Conzen said.

So what are the practical applications of the research?

The findings may suggest molecular biomarkers, or targets, for preventive intervention in breast cancer, she said.

“Many questions remain,” Conzen added. “One of the things we did note is that the isolated animals were much more vigilant, less exploratory. They released more of a stress hormone when we added another stressor to the situation [besides the isolation].”

Thea Tisty, a pathology professor at the University of California, San Francisco, who is familiar with the findings, called the research “a very exciting beginning.”

The implication is that perceived or actual stress from outside can affect which genes get turned on or off. If the research findings bear out, it could lead to a way to catch tumors in their formation before they become tumors and suppress them, she said.

Another expert speaking at the briefing cautioned that the findings, while exciting, are only preliminary and based only on animal studies.

“This is an area that has a long way to go in terms of understanding how these factors play out in humans,” said Caryn Lerman, the Mary W. Calkins Professor of Psychiatry at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.