Viagra could help women too, but not how you think…

Metastatic Breast Cancer in Pleural FluidSince first coming on the market in 1998, the erectile dysfunction drug Viagra has improved the sex lives of countless men. Now new research has suggested that phosphodiesterase 5 (PDE5) inhibitors like Viagra could also help women – but not how you think.

Researchers in California have shown that sildenafil (Viagra) and a similar drug called vardenafil can improve the delivery of the chemotherapeutic drug Herceptin (trastuzumab) in women with breast cancer that has spread to the brain. Their studies in mice have found that PDE5 inhibitors help Herceptin cross the blood vessels of brain tumours into the heart of the cancer, thus improving the therapeutic efficacy of Herceptin for brain metastases from primary tumors.

Although only about 22,000 patients in the US are diagnosed with a primary brain tumor each year, nearly 10 times that many people develop brain tumors from cancers that began elsewhere in the body. For example, one study found that 36% of women receiving Herceptin for breast cancer developed brain metastases.

These secondary brain tumours are very hard to treat thanks to the fact that chemotherapy drugs can’t cross the walls of the tumour’s blood vessels – the blood-brain tumor barrier – and into the cancer. “Mother Nature created this barrier to protect our brains from dangerous substances, but here we need to get through the barrier to deliver the drugs, and that’s a problem,” said study author Julia Y Ljubimova, a research scientist at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute in Los Angeles.  This means that drugs that can kill the primary tumour in the breast or lung aren’t effective on secondary tumours in the brain.

Ljubimova and her colleagues looked at the effects of PDE5 inhibitors on drug delivery in mice whose brains had been implanted with human lung and breast tumors. Oral administration of vardenafil to such mice doubled the uptake of Herceptin by brain tumours. Importantly, vardenafil had no effect on the uptake of Herceptin in neighbouring healthy tissue, an unfortunate effect of many chemotherapy drugs that is responsible for making cancer patients feel so awful and lose their hair.

Furthermore, combination treatment of mice with vardenafil and Herceptin increased the survival time of these mice by 20% compared with those that received Herceptin only.  This effect was only seen in mice whose brain tumours were positive for HER2, the growth factor targeted by Herceptin, and not those that were HER negative, indicating that the survival benefit was indeed due to an increase in the amount of Herceptin reaching the tumors.

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“Now that we’ve demonstrated that big molecules can cross the blood-brain tumor barrier, we’re going to continue this strategy with other big molecule drugs, such as nanomedicine drugs” said Ljubimova. “This opens a new world for brain tumor treatments.”

Hu J et al. (2010) Phosphodiesterase Type 5 Inhibitors Increase Herceptin Transport and Treatment Efficacy in Mouse Metastatic Brain Tumor Models. PLoS ONE 5 (4). DOI: 10.1371/journal.pone.0010108

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Got breast cancer? Get to your greengrocers!

Fruit & VegFresh fruit and vegetables can inhibit the growth of breast cancer tumors and reduce the risk of death in women who already have breast cancer, say two new studies.

The first study is one of several on the effects of fresh apple extracts in rats.  Whole apple extracts have strong antiproliferative and antioxidant activities, thought to be a result of the combination of phytochemicals in the fruit.

This study found that giving rats with mammary tumors a dosage of apple extracts equivalent to one apple a day in humans seriously curtailed the likelihood of tumor growth.  In total, only 57% of rats fed low doses of apple extracts experienced rapid tumor growth over the 24-week study compared with 81% of control animals, who received no apple extracts whatsoever.

Strikingly, only 23% of the rats fed high doses of apple extracts showed signs of tumor proliferation. Scaled up, a human would need to consume six apples a day to benefit from this protective effect.

Rui Hai Liu, Cornell associate professor of food science and one of the study’s authors, said, “We not only observed that the treated animals had fewer tumors, but the tumors were smaller, less malignant and grew more slowly compared with the tumors in the untreated rats.”

A second study of 1,901 women with early-stage breast cancer found that a healthy diet of fruit, vegetables, whole grains, and poultry reduced the risk of death from any cause.

The risk of death in women who stuck rigidly to a ‘prudent’ diet was almost 50% lower than that in women who paid less attention to what they ate.  On the other hand, the risk of death in women who ate a Western diet comprising a high intake of red and processed meats and refined grains was much higher than in less unhealthy women.  These observations were generally not modified by physical activity, being overweight, or smoking.

Interestingly, neither dietary pattern was associated with risk of breast cancer recurrence or death from breast cancer.

The authors conclude that “women diagnosed with early-stage breast cancer might improve overall prognosis and survival by adopting more healthful dietary patterns.”

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When NOT to screen for cancer

Cancer screeningAnnual screening for prostate cancer may not be required in many elderly men, whereas routine screening for breast cancer should probably never have been implemented, say two separate studies published this week. These studies raise questions as to whether regular screening for common cancers is really necessary and, if so, in which groups.

In the first study, due for publication in the Journal of Urology, the authors assessed 849 men aged from 40 to 92 who had been followed up for 10 years as part of the Baltimore Longitudinal Study on Aging.

During this time period, the men had undergone an average of four tests to measure prostate specific antigen (PSA) levels. PSA level in the blood is used to screen for prostate cancer: if a man has a blood PSA level of of 4.0 ng/ml or higher, it is likely that he has prostate cancer.

The authors found that in a subgroup of men aged 75 years or older who had a PSA level of below 3.o ng/ml – well within the normal range – none died of cancer and only one developed high-risk prostate cancer.

In the US and the UK, men over the age of 50 are advised to undergo annual prostate cancer screening. The findings of this study imply that routine screening may not be needed those who are over 75 and have a normal PSA level, as such individuals are unlikely to die of or experience aggressive prostate cancer during their remaining life. Even if PSA levels indicate that a man over 75 DOES have prostate cancer, it’s likely that he’ll die of something else rather than the malignancy.  In such cases men could forgo risky therapy and avoid the nasty side effects that can seriously affect quality of life.

Speaking to Reuters, Dr H Ballentine Carter of Johns Hopkins University in Baltimore, one of the researchers contributing to the study said, “For the overwhelming majority of men over age 75, discontinuing PSA screening is probably a very safe thing to do”.

As for women, an analysis in the BMJ has highlighted the risks associated with mammography – including a high rate of false positives – and suggests that in many cases the risks inherent in routine screening for breast cancer outweigh the benefits.

The authors of this study argue that the NHS Cancer Screening Programmes leaflet about mammography, Breast screening: the facts, is unbalanced in its portrayal of the positives and negatives of screening and constitutes “one sided propaganda about breast screening”.

They suggest that the leaflet overplays the benefits of breast cancer screening, such as the possibility that screening leads to fewer mastectomies.  Various studies indicate that the number of mastectomies actually increases when screening is introduced, they point out. The authors even dispute the statement that screening saves lives, highlighting trials showing that screening does not decrease total cancer mortality.

The authors also opine that the leaflet downplays the risks of breast cancer screening, like the possibility of being overdiagnosed, which with mammography is ten times more likely than being accurately diagnosed.  “No mention is made of the major harm of screening – that is, unnecessary treatment of harmless lesions that would not have been identified without screening,” they write.

The analysis concludes that breast cancer screening is associated with less benefit and substantially more harm than previously thought and that mammography screening programmes would probably not have been initiated if the individuals who wrote the policies 20 years ago had had the evidence available today.

So should prostate cancer and breast cancer screening programmes be cut back? Doing so would avoid the consequences of false positives and would save health care providers millions of pounds in diagnostic costs.

What do you think? Would you stick to your yearly screening appointments regardless of the risk of being misdiagnosed and subjected to unneccessary treatment, just in case one day screening does catch a malignant but treatable lesion that would have otherwise been missed? Or would you rather steer clear of the hassle of screening and the stress of a false alarm?

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Attitude has no effect on survival in women with breast cancer

Many patients with cancer feel that their attitude towards the ‘fight’ is an important part of beating the disease, but maintaining a positive perspective is pretty tough in the face of a life-threatening malignancy.

A large, population-based study published in the Journal of Clinical Oncology has now found that psychosocial factors such as fighting spirit and fatalism have no effect on survival in patients with breast cancer. The authors Phillips et al. emphasize that their results could allay the concerns of anxious women who believe that their mental attitude towards breast cancer will affect their likelihood of survival, and could in fact lift the burden of responsibility such women may feel.

Phillips et al. studied 708 Australian women diagnosed with nonmetastatic breast cancer before the age of 60 (average age 40 years old). At study entry approximately 11 months after diagnosis, all women completed an array of psychosocial tests that were designed to assess factors such as anxiety and depression, coping style, and social support. These women were then followed up for an average of 8.2 years.

In total, 33% of women experienced distant recurrence of their cancer and 24% died during follow-up. Once the patient data had been adjusted to take into account other factors that affect chances of recovery, such as tumour size, no associations could be found between psychosocial factors and either distant disease-free survival or overall survival.

The authors conclude that their study does not support the controversial theory that psychosocial factors influence survival after breast cancer. They state, “This should be reassuring for women, particularly those who experience substantial levels of psychosocial distress after their diagnosis.”

It is important to note, however, that therapies that aim to reduce psychosocial stress in women with breast cancer should not be discounted, as such interventions do seem to improve quality of life.

K.-A. Phillips, R. H. Osborne, G. G. Giles, G. S. Dite, C. Apicella, J. L. Hopper, R. L. Milne (2008). Psychosocial Factors and Survival of Young Women With Breast Cancer: A Population-Based Prospective Cohort Study. Journal of Clinical Oncology 26 (28): 4666-4671 DOI: 10.1200/JCO.2007.14.8718

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