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WEDNESDAY, Sept. 10 (HealthDay News) -- Tumors often rebound rapidly following chemotherapy, and oncologists may now understand why: Blame the body.

They may also have found a new way to prevent that rebound effect, at least in their mouse model.

Robert Kerbel, of the Sunnybrook Health Sciences Centre, Toronto, and the University of Toronto, led an international team of researchers that discovered that some -- but not all -- chemotherapeutic agents damage not only cancerous tissue, but also the blood vessels that supply that tissue with oxygen and nutrients.

That damage, in turn, induces the body to mobilize so-called "circulating endothelial progenitor" (CEP) cells, blood vessel precursors that home to and repopulate the damaged tumor, enabling it to regenerate.

That effect appeared to be mediated by a cellular growth factor called SDF-1alpha. Fortunately, co-administration of drugs that either block SDF-1alpha or directly block blood vessel development appears to blunt that response -- making the chemotherapy regimen more effective.

"We view this as a yin-yang, action-reaction situation," Kerbel said. "The primary action is the effect of the drug on the tumor. The reaction is the host response, which compromises part of the action, and you want to blunt that with an anti-angiogenic drug and/or something targeting this [protein] SDF-1. That's what this paper is all about."

Should these findings be validated in human subjects, they could potentially explain why anti-angiogenic therapies such as bevacizumab (Avastin) work better with some chemotherapeutics (such as paclitaxel, also called Taxol) than others. They may also explain why tumors seem to rebound so rapidly following chemotherapy treatment, as well as offering up a novel drug target (SDF-1) to suppress this effect. On a more practical level, the findings could help researchers decide which combination therapies to test in clinical trials, and which to put on the back burner.

"These data give a potential explanation for why some [drug] combinations have given much better bang for the buck than others," said Dr. Kathy Miller of the Indiana University School of Medicine in Indianapolis, who co-authored an editorial on Kerbel's study.

The findings were published in the September issue of the journal Cancer Cell.

The question at the heart of this study involves a relatively new class of anticancer drugs called anti-angiogenesis therapies. Angiogenesis is the process of new blood vessel growth, and it is critical to tumor development. That's because the growing tumor mass requires ever-increasing amounts of nutrients and oxygen to survive. Anti-angiogenic therapies target this process to choke off the tumor's supply lines.

Oncologists rarely if ever prescribe anti-angiogenic therapies in isolation; they almost always are paired with a traditional chemotherapy. Yet it turns out that only in certain cases does the anti-angiogenic drug provide a benefit above that of the standard cytotoxic agent. In other cases, the combination was no better than the chemotherapeutic agent alone. Kerbel wanted to understand why.

In earlier work, his team found that when mice are given certain cytotoxic agents, CEP cell levels in the bloodstream spiked rapidly, within three or four hours, and then migrated to the damaged tumor, where they began repairing the damage.

As Kerbel explained, this was a departure from conventional oncology wisdom.

"The ability to recover from cytotoxic chemotherapy has often been viewed as an intrinsic property of the tumor -- they are Hercules, they have the property to survive and rebound very quickly after therapy," he said. "What we say in the [earlier] paper is, perhaps a part of the ability to repopulate is not just a function of the tumor cell population, but also of the host."

The current study was a follow-up in which Kerbel and his team systematically analyzed different chemotherapeutics for their ability to induce this host CEP response.

"We found there are some chemotherapy drugs -- for instance, taxanes -- that are very, very effective in inducing in mice this bone marrow response. There are other drugs like gemcitabine that are not very effective at all in inducing this response," Kerbel said.

In other words, some drugs cause CEP levels to spike, while others do not. "We don't know why there are these differences," he adds, "but there are these differences."

Importantly, the researchers also showed that co-administration of traditional chemotherapeutics with anti-angiogenic agents could blunt this CEP response. And, they implicated the body's own growth factor SDF-1alpha in mounting that response.

"We put forward the notion that drugs that target SDF-1 or its receptor, CXCR4, maybe they might be useful anticancer agents, not on their own, but combined with certain cytotoxic agents," said Kerbel.

"I think [this study] is very exciting, looking at it from a potential impact on how we use different drugs in the clinic," added Miller.

Not only can the data potentially explain why some drug combinations work better than others, she said, "it also gives a much better way to screen potential combinations in the lab."

Preliminary clinical data presented in the paper suggests the mouse findings will be replicated in human patients, said Kerbel.

Yet that doesn't mean doctors can now change clinical practice, said Dr. Alan Sandler, Medical Director of Thoracic Oncology at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

"This is really early preclinical stuff," he said. "There's already data out there showing that anti-angiogenic agents work. This is helping to explain perhaps why it may work."

More information

For more about anti-angiogenesis treatment strategies, visit the American Cancer Society  .

TUESDAY, Sept. 9 (HealthDay News) -- The most comprehensive global snapshot ever taken of lung cancer diagnoses and related death rates among patients who have never smoked has found that, contrary to prior indications, lung cancer risk is not on the rise.

The analysis also revealed that the lung cancer death rate among those who have never smoked is higher among men than women.

Both findings stem from an enormous collaborative international effort that draws on information from 13 large studies and 22 cancer registries, and represents upwards of 2 million men and women living in 10 countries across North America, Europe, Asia, the Middle East and Africa.

"The great majority of lung cancers are caused by smoking," stressed study author Dr. Michael Thun, head of epidemiological research at the American Cancer Society. "But there has been a lot of interest lately in those lung cancer cases that affect patients who have never smoked, in part because of prominent nonsmoking patients who have had the disease in recent years, like Dana Reeve," who died from the disease at the age of 44 in 2006.

"This increased interest has led to a lot of concern, misperceptions and misconceptions regarding the state of risk and susceptibility," Thun added. "So, this work addresses this speculation, firstly by finding that, over the last 50 to 70 years, there has been no increase in lung cancer among people who have never smoked. And secondly, that the popular belief that 'never-smoked' women are more likely to develop the disease than men turns out not to be the case. And thirdly, that African-Americans have a higher death rate than whites."

Thun and his colleagues collectively published their observations in the September issue of PloS Medicine.

Their conclusions are based on incident and mortality rates for lung cancer among more than 630,000 and 1.8 million men and women (respectively) who had never smoked, and who had participated in one of 13 different large studies (each involving a minimum of 20,000 participants) conducted in North America, Europe or Asia.

The authors also reviewed cancer registry statistics specifically regarding women that had been compiled some time between 1983 and 1989 in 10 countries (across Asia, Africa, Europe, the Middle East, China and India). In all these places, the rate of smoking among women was known to be relatively low.

After digesting these and other variables, Thun and his associates concluded that since the 1930s, there has been little to no change in either lung cancer incident or death rates among lifelong non-smoking American men and women.

The research team further determined that lung cancer death rates are higher in men who never smoked than women, and that this apparent "mortality gap" appears to widen as people age.

However, in terms of lung cancer incidence among this group, the rate among women outstripped that of men for those under the age of 70, particularly among women between the ages of 50 and 59. Yet that dynamic reversed after age 80, when more men begin to be diagnosed with the disease.

Nonsmoking black men and women were found to have a higher death rate from the disease than those of European descent, while black women also appeared to have a higher incidence rate as well. No conclusion could be drawn regarding incidence among black men.

Lung cancer incidence was also observed to be two to three times higher among Asian women living in East Asia (Philippines, Hong Kong, Japan, and Singapore) as compared with women living in Western countries with similarly low female smoking rates. And overall, Asian men and women living in Asia (but not those of Asian descent living in the United States) appear to face a higher lung cancer death rate than people of European descent.

Thun noted that 85 percent to 90 percent of lung cancer cases are caused by smoking, which translates into roughly 1.4 million lung cancer deaths across the globe each year.

Nevertheless, he pointed out that the pool of remaining patients who develop the disease due to other factors is a public health issue that is worthy of investigation.

"We're talking about figures that are right up there with brain cancer in terms of the hard numbers of patients," he noted. "And relative to other cancers, lung cancer research is under-funded. So, the value of this kind of broad effort to better understand the problem is immense."

Dr. Neil Schachter, a professor of pulmonary medicine at Mount Sinai Medical Center in New York City, agreed that the current analysis addresses an important issue, given that the number of nonsmoking lung cancer patients is "small, but obviously significant".

"But though the findings are not that surprising and certainly form an impressive observation, this work needs to be followed up," Schachter cautioned. "For example, with respect to men having a higher death rate, it is important to recognize that men may have more co-morbidities than women. That is, they have more associated diseases. And the fact you have associated diseases may make you more prone to dying from the complications of lung disease. So, there are a lot of factors to consider before coming to any strong conclusions."

More information

For more about lung cancer and risk factors, visit the American Cancer Society  .

WEDNESDAY, Sept. 3 (HealthDay News) -- While tremendous progress in screening and treatment for breast cancer has been made in recent years, some 184,000 new cases of breast cancer will be diagnosed in the United States in 2008, and about 41,000 women will die of the disease.

Researchers are now focusing their efforts on reducing these numbers even further.

Four studies being presented this week at the American Society of Clinical Oncology's 2008 Breast Cancer Symposium in Washington, D.C., highlight both areas of progress and areas that need extra emphasis.

A screening technique known as molecular breast imaging (MBI) detected three times as many breast cancers in women who have dense breasts and who are at a higher risk of developing the disease. These findings suggest that MBI could one day be added to conventional mammography.

Using an injected radiotracer (provided, for this study, by Bristol-Myers Squibb), MBI is able to detect differences in the behavior of cancer tissue as compared to normal tissue.

In this study, MBI detected 10 of 13 cancers among 375 patients completing a 15-month follow-up period. Mammography, by contrast, detected three of 13 cancers.

"If we had had a combination of both techniques, we would have detected 11 of 13 cancers," said study author Carrie B. Hruska, a research fellow in the department of radiology at the Mayo Clinic in Rochester, Minn. "MBI detected more cancers than screening mammography but didn't produce more false positive results."

Hruska spoke at a Wednesday teleconference with authors of the three other studies.

Also, the number of biopsies that actually resulted in cancer was much higher with MBI (28 percent) than with mammography (18 percent).

"Based on the results, MBI has shown great promise as a valuable adjunct to screening mammography in women with dense breasts and who are at an increased risk of developing cancer," Hruska said.

But while relatively inexpensive and easy to use, MBI is not yet widely available.

"This is an area that is very important, and where we really need to do further work," said Dr. Eric Winer, moderator of the teleconference and director of the breast oncology center at Dana-Farber Cancer Institute in Boston.

A second study, conducted by researchers at Johns Hopkins University, debunks the long-held notion that women in rural areas are more likely to chose mastectomy over lumpectomy because of difficulty traveling to radiation facilities.

Radiation is considered standard-of-care for women after they have received a breast-conserving lumpectomy, although not for women who undergo a mastectomy.

There were no notable differences between radiation rates following lumpectomy for women in rural areas as compared with women in urban areas, although the study did confirm that more women in rural areas (59.9 percent) opted for mastectomy, versus 44.9 percent of women in urban areas.

"The disparity . . . is not necessarily due to the availability of radiation therapy but to other factors," said study author Dr. Lisa K. Jacobs, an assistant professor of surgery at Johns Hopkins University in Baltimore.

"This would seem to suggest that if a woman in a rural area chooses to have a lumpectomy, she will most likely not fall through the cracks in terms of getting radiation, which is somewhat reassuring," Winer said. "But it would be interesting to look at this further."

In a third study, researchers at M.D. Anderson Cancer Center in Houston found that older black women undergoing lumpectomy for early-stage invasive breast cancer were less likely to receive recommended post-surgery radiation therapy than their white counterparts.

Only 65 percent of black women received radiation, compared with 74 percent of white women. "The difference is concerning, given that radiation after lumpectomy is generally considered standard therapy," said study author Dr. Grace Smith, a postdoctoral fellow in the department of radiation oncology at Anderson.

Disparities also existed in the younger range (women aged 65 to 70) of this older group, who were less likely to have medical conditions precluding radiation therapy. Here, 71 percent of black women received potentially lifesaving radiation versus 81 percent of white women.

The largest disparities were evident in the East South Central region of the United States, the Pacific West and New England.

"What seems to be happening is that the use of conservative surgery and radiation opens the door for disparities to play a greater role in limiting access to care," Winer said. In this two-step process (surgery plus radiation), Winer added, "it is possible for women to fall through the cracks."

The final study addressed women with HER2-positive breast cancer, which traditionally has a worse prognosis than other forms of breast cancer.

Chemotherapy and treatment with Herceptin (trastuzumab) before surgery results in a "pathologic complete response," meaning no evidence of invasive disease in the breast or lymph nodes existed in many patients.

Patients who did not have this complete response were three times more likely to have a recurrence, the researchers from M.D. Anderson reported.

In about one-third of those not achieving a complete response, the cancer had converted from HER2-positive disease to HER2-negative disease, meaning it was no longer responsive and had possibly become resistant to HER2-specific therapies such as Herceptin.

The authors stressed the importance of reassessing tissue for HER2 status after preoperative treatment.

More information

Visit the National Cancer Institute for more on breast cancer.

WEDNESDAY, Sept. 3 (HealthDay News) -- Taller men are at greater risk for prostate cancer and more likely to have cancer that progresses quickly, a new British study suggests.

The researchers doubt that height itself is the reason for the increased risk, but it may serve as a marker for something biological associated with developing cancer.

And other cancer experts said other risk factors for the disease are far more significant than being tall.

"We believe that factors that influence height -- not height itself -- could also influence cancer, said lead study researcher Luisa Zuccolo, of the University of Bristol Department of Social Medicine. "One plausible mechanism behind this association could be the insulin-like growth factor-1 system, which new lines of inquiry should address."

The findings were published in the September issue of the journal Cancer Epidemiology, Biomarkers & Prevention.

For the study, Zuccolo's team collected data on more than 9,000 men with and without prostate cancer and reviewed 57 relevant studies. The researchers found that the risk of developing prostate cancer increased about 6 percent for every 3.9 inches in height above the shortest men in the study. The average height of the men in the study was 5 feet, 7 inches.

In other words, a man who's a foot taller than the shortest person in the study would have a 19 percent increased risk of developing prostate cancer. The statistical data supporting this finding was weak, the researchers noted.

However, the researchers did find stronger evidence that height was associated with more aggressive tumors. For every 3.9 inches of increased height, the risk of a high-grade tumor rose 23 percent, Zuccolo's group found.

Compared with the main risk factors for prostate cancer -- such as aging, ethnicity and a family history of the disease -- the magnitude of the additional risk of being taller is small, Zuccolo said.

"We do not believe that height should interfere with preventive or clinical decisions in managing prostate cancer," Zuccolo said. "However, although not yet directly transferrable to medical practice, results from this research are of great scientific interest, especially given that so little is known of preventable causes of prostate cancer."

Dr. Anthony D'Amico, chief of radiation oncology at Brigham and Women's Hospital in Boston, said the study findings may be due to chance and not represent a real association.

"When you do a study like this, where you look at a very common attribute like height, eye color or skin color, and then you look at a very common disease like prostate cancer, you can find association that may just be by chance," he said.

There may be an association between height and a high-grade prostate cancer, D'Amico added. "But that association should not be taken to mean that if you are tall that there is something about being tall and getting high-grade prostate cancer. It could simply be that being tall is a surrogate for something else biological, which may be what is causing the effect."

"I don't think that this study convinces me, or makes me conclude that height in and of itself is a risk factor, and we should start screening earlier in men who are above a certain height," he said.

Dr. Stephen Freedland, an associate professor of urology and pathology and director of outcomes and translational research at the Duke Prostate Center at Duke University Medical Center, thinks other risk factors for prostate cancer are much more important than height.

"This is something I'd hate to see people get all worried about," he said. "If you eat right, take care of yourself, prevent yourself from being obese, I think you are doing the best you can. Everyone, short or tall, should be checked regularly."

More information

Learn more about prostate cancer from the American Cancer Society  .