Researchers at Cleveland Clinic have discovered that a gene – known as an androgen receptor (AR) – is found in both prostate and breast cancers yet has opposite effects on these diseases.

In prostate cancer, the AR gene promotes cancer growth when the gene is “turned on.” In breast cancer, the AR gene promotes cancer growth when the gene is “turned off,” as is often the case after menopause, when AR production ceases in women.

What this means is that treating prostate and breast cancers require completely opposite approaches to AR. In treating prostate cancer, the strategy should be to block AR; in breast cancer, the strategy should be to support AR production.

Researchers from Cleveland Clinic’s Lerner Research Institute, including Charis Eng, M.D., Ph.D., Chair, Genomic Medicine Institute; Robert Silverman, Ph.D., and Warren Heston, Ph.D., both of the Department of Cancer Biology; focused on whether the androgen receptor (AR) molecule offers evidence of the tumor suppressor protein PTEN. The research discovered that AR inhibits PTEN expression in prostate cancer cells, but stimulates it in breast cancer cells.

The conclusions, published in the Oct. 21, 2011 issue of Oncogene, explain why prostate cancer progression is associated with increased AR expression (and a common prostate cancer treatment strategy involves blocking AR), while most breast cancers occur post-menopause, after AR production has ceased (making AR supplementation a strategy for treating breast cancer).

Dr. Eng and her colleagues have mapped the interaction between AR and PTEN in both prostate and breast cancer cells, which suggests that this interaction activates or represses subsequent gene expression depending on organ-specific cofactors. Although PTEN is a known tumor suppressor, and loss of PTEN expression has been associated with numerous cancers (including breast and prostate cancers), its regulation has not been well understood. The current data provide new information regarding PTEN regulation, and suggest that identifying regulatory cofactors will be a valuable next step in determining cancer risk, as well as potential new therapies.

“We now see how androgen affects PTEN expression – and ultimately cancer,” said Dr. Eng. “Our observations help explain why this prostate cancer risk can be halved by drinking red wine, which increases PTEN expression. Our data also suggest that treatment of the exact same cancer must be personalized for males and for females.”

Source: Dan Doron, Cleveland Clinic, via EurekAlert

“The results show that men who took vitamin E alone are actually at a higher risk of developing prostate cancer by about 17 percent, compared with a placebo,” said Dr. Eric Klein, who treats prostate patients at the Cleveland Clinic and co-chaired the study.

Researchers studied the effects of vitamin E on more than 35,000 men over the course of seven years because they originally thought vitamin E – and selenium – would decrease the risk of developing prostate cancer.

The study’s results were not what the researchers expected.

Researchers said they need to determine exactly why vitamin E can increase the chances of developing prostate cancer.

“The increased risk really emerged after men stopped taking the vitamin E,” Klein said. “People think of vitamins as innocuous substances, but in fact, that’s not true. They’re active agents; they’re part of our normal physiology and getting too much of things that are normal for us can sometimes be harmful.”

Dr. David Samadi, a Fox News Medical A-Team member and chief of robotics and minimally invasive surgery at Mount Sinai School of Medicine in New York City agreed. “We now have a better understanding of the relationship between vitamin E and prostate cancer. Their key finding…is the reason I am so cautious of prescribing alternative medicines.We should base our practice off of evidence-based clinical trials.”

In the U.S., prostate cancer is one of the most common types of cancers in men.

Source: Fox News

The National Institute for Health and Clinical Excellence (Nice) said that the medicine, called cabazitaxel, was not a cost-effective treatment for men who have already undergone hormone therapy.

It said that although the drug did extend survival for patients with advanced prostate cancer, it was “concerned” about the side-effects experienced in clinical trials and that at an average cost of £22,000 per patient it was too expensive.

The move comes after an important study commissioned by The Lancet Oncology warned that the cost of cancer care is becoming unsustainable in developed countries, and that it makes no sense to keep giving “toxic” and costly drugs to patients with just a few weeks to live.

Sir Andrew Dillon, the chief executive of Nice, said: “The committee concluded that cabazitaxel would not be a cost effective use of limited NHS resources.”

But Owen Sharp, chief executive of the Prostate Cancer Charity, said: “Cabazitaxel is an important treatment, only recently licensed for use here in the UK, which can help to extend the lives of men in the final stages of prostate cancer for whom existing treatments have stopped working.

“These men currently have very few treatment options open to them when their cancer reaches this advanced stage.

“Increasing the number of treatments that may extend the lives of these men and allow them to spend precious time with their families is essential.”

Prostate cancer is the most common form of the disease among British men, with 37,000 cases diagnosed every year.

Some men live for years with slow-growing tumours, but in other cases it develops aggressively and kills after spreading to other organs.

Treatments often attempt to reduce the production of testosterone, a hormone that fuels the growth of the tumours, but patients can develop resistance to this type of therapy.

In clinical trials, men with advanced prostate cancer who were given cabazitaxel in combination with prednisone, a drug that suppresses the immune system, lived for an extra 10 weeks.

But Nice said there was “uncertainty” about the new drug’s effect on patients’ hearts and livers, and it did not meet its criteria for being considered as an end-of-life drug worthy of additional funding.

It means that anyone who hopes to obtain the new type of chemotherapy on the NHS must make an individual application through the Cancer Drugs Fund.

Nice is still assessing the value of a daily pill that can treat advanced prostate cancer, called abiraterone acetate, which is believed to have kept the Lockerbie bomber alive longer than expected.

Source: The Telegraph

Led by Dr David Ørsted at the Copenhagen University Hospital, Herlev, the first study shows that men diagnosed with benign prostate enlargement have an increased risk of developing and dying from prostate cancer. The second study shows that monitoring prostate-specific antigen levels can be used to predict the long-term risk of healthy men developing and dying from prostate cancer. Both could lead to more efficient and cost-effective screening for prostate cancer, with reductions in over-diagnosis and unnecessary treatment.

According to European Cancer Observatory statistics, over 70,000 men die from prostate cancer in the EU every year. Prostate cancer and benign enlargement of the prostate gland, known as benign prostatic hyperplasia, share common features. Growth of the gland is dependent on hormone levels in both conditions and both respond to anti-androgen treatment, but until now benign prostatic hyperplasia has not been considered a precursor to the development of a tumour.

Researchers investigated the association between the two conditions by examining data from five national registries, on a total of 3,009,258 Danish men.

The sample included 53,315 diagnoses of prostate cancer and 25,459 cases of death due to prostate cancer. Clinical benign prostatic hyperplasia was determined by records of hospitalisation (187,591 men) and/or operations for the condition (77,698 men) between 1980 and 2006, and the use of certain drugs indicated for the condition between 1995 and 2006 (143,365 men and 47,465 men respectively for the two treatments). The reference group was men without benign prostate hyperplasia.

Over 27 years, the study found that clinical benign prostate hyperplasia was associated with a two to three-fold increased risk of men developing prostate cancer, and with a two to eight-fold increased risk of them dying from prostate cancer.

“Benign prostatic hyperplasia and prostate cancer are the most common prostatic conditions with a large number of incident and prevalent cases each year. A possible association has been debated for several years but previous studies have generated ambiguous results. Our study is the largest to date and has consistent results showing an association,” research team member Dr Stig Bojesen will tell the congress.

Additional research is needed to determine whether benign prostate enlargement could be a possible cause of prostate cancer, but the results already have important implications given the large number of patients affected. “The possible clinical implication of our study might be that physicians treating men with benign prostatic hyperplasia should follow these men carefully, to ensure early diagnosis and treatment of a possible prostate cancer, thereby enhancing the chance of curative treatment. However, our study does not allow us to suggest the optimal surveillance programme for these men. This question should be addressed in future studies,” says Dr Bojesen.

The second Danish study, also led by Dr Ørsted, looked at whether prostate-specific antigen levels could predict prostate cancer incidence and mortality in the general population.

Prostate-specific antigen is a protein produced by the prostate gland. Healthy men have low levels of the antigen in their blood, and raised levels are considered an indicator of prostate cancer as well as other conditions of the gland. However, it is largely unknown whether antigen levels in healthy men predict long-term risk of developing prostate cancer.

Researchers looked at blood collected from 4,383 men aged between 20 and 94 years of age from the general population, who had taken part in the Copenhagen City Heart Study and followed them from 1981 through to 2009. They measured baseline levels of prostate specific antigen and investigated whether this correlated with later prostate cancer incidence and mortality.

During the 28 years of follow-up covered by the Heart Study, 170 men in the sample developed prostate cancer and 94 died from the disease. Measuring the antigen levels, the researchers found that stepwise increases in prostate-specific antigen predicted a 3-44 fold increased risk of prostate cancer and a 2-12 fold increased risk of prostate cancer mortality.

They also found that the absolute 10-year risk of prostate cancer was 11-22% in those with prostate-specific antigen levels of 4.01-10.00 ng/ml and 37-79% in those with levels above 10.00 ng/ml.

The ranges are wide and the higher risk for some men can be explained, Dr Ørsted will tell the congress. “The high risk for some men is probably due to some of the participants having already developed sub-clinical prostate cancer at the time of their entry to the study. These men would have had a shorter time from study entry to diagnosis and consequently, higher risk estimates.”

The results could be used to target specific sections of the population for screening. “One of the major problems in prostate cancer is over-diagnosis. Furthermore, two large randomised studies have shown that the benefit of general screening for prostate cancer is limited,” explains Dr Ørsted. “Our results indicate that physicians could focus screening efforts on men with higher baseline prostate specific antigen values while men with lower levels could avoid having frequent and unnecessary diagnostic examinations. This could reduce over-diagnosis and unnecessary treatment as well as reduce expenditure in already strained health systems,” he says.

President of ECCO, Professor Michael Baumann, said: “These studies demonstrate how important it is to have good cancer registries and skilled cancer epidemiologists available. Large cancer registries, which contain high quality data and link to several items, enable us to address specific questions; for example, whether there is a link between benign prostate hyperplasia or long-term PSA levels and the risk of prostate cancer. Such research allows us to draft hypotheses for further research and to create more efficient screening and prevention programmes.”

ESMO spokesperson, Professor Hein Van Poppel, Director of the European School of Urology, commented: “The first study indicates the need for future research to focus on how to follow patients with benign prostatic hyperplasia in order to recognise an eventual cancer in time. PCA3, genetic fusion markers or methylation markers could be explored for this purpose.

“For PSA screening, the ideal screening timetable needs to be investigated. It could well be that screening needs to start at an age where there is no interference from benign prostatic hyperplasia in PSA production, i.e. at age 40; by repeating the PSA measurement at 45 and at 50 years old, the PSA slope can probably recognise those with a high likelihood of ever developing cancer, but also those who will not need further screening because their chance of ever developing significant prostate cancer is minimal.”

Source: Saffina Rana, ECCO-the European CanCer Organisation, via EurekAlert

The researchers emphasize that this new data should serve as a reminder to physicians to carefully weigh the risks and benefits of biopsy for individual patients and take all precautions to prevent infections and other complications.

The Johns Hopkins team’s findings are the result of the largest analysis ever performed of Medicare records of American men age 65 and older who underwent prostate biopsies in the last two decades. They found that having a prostate biopsy makes patients more than twice as likely to need hospitalization in the immediate post-procedure period. Those hospitalized had a range of complications, such as bleeding and infection, as well as flare-ups of underlying medical conditions, such as heart failure or breathing disorders.

Overall, mortality rates in men undergoing prostate biopsies did not increase. However, men hospitalized with biopsy-related infections had a 12-fold higher risk of death compared to men who did not have a biopsy.

“Prostate biopsy is an essential procedure for detecting prostate cancers,” says Edward Schaeffer, M.D., Ph.D., a Johns Hopkins urologist and oncologist and the study’s senior investigator. “Coupled with appropriate screening, prostate biopsies save lives. However, it is important for men to be aware of the possible risks of prostate biopsies, which are often described as simple outpatient procedures,” adds Schaeffer, an associate professor at the Johns Hopkins University School of Medicine and its Brady Urological Institute.

In their study, the researchers examined the frequency of biopsy related complications that required hospitalization in more than 17,400 men age 65 and older from 1991 to 2007. They compared these rates to a cohort of 134,977 men during the same time period with similar characteristics who did not undergo a prostate biopsy. The researchers only looked at hospital admissions, not men whose complications were treated in an emergency department or outpatient setting.

While the rate of hospitalization following prostate biopsy has declined steadily since 1991, the researchers found that the rate of hospitalization during the time period was still two-fold higher among the men who had a biopsy (6.9 percent compared to 2.9 percent).

There was also a steady rise in the rate of serious infection-related complications. At the onset of the study in 1991, fewer than 0.5 percent of men were admitted to the hospital because of an infection diagnosed following a prostate biopsy. This rate remained stable until 2000, when rates of infection-related complications began to increase to more than 1.2 percent in 2007.

“Antibiotics are routinely given to men at the time of biopsy, and the fact that infections serious enough to cause hospital admissions have been on the rise makes us think that these types of complications are occurring because of a steady increase in antimicrobial resistance rates in America,” says Schaeffer.

Co-author H. Ballentine Carter, M.D., professor of urology and oncology at the Johns Hopkins University School of Medicine, says, “Based on these findings, we believe that more needs to be done to reduce potential complications. It is important for urologists to determine if a biopsy is appropriate for an individual patient and also if the patient is at increased risk for a biopsy- related complication.”

The researchers say that prostate biopsies should only be performed with strict adherence to medical guidelines, and after all potential risks and benefits have been reviewed with patients. More than 1 million prostate biopsy procedures are performed each year in the United States to diagnose and monitor prostate cancer, which is the second most common cause of cancer death among men.

Source: Ellen Beth Levitt, Johns Hopkins Medical Institutions, via EurekAlert