Wednesday, March 10, 2010

HRT linked to LC risk

Women who take hormone replacement therapy (HRT) are at an increased risk of developing lung cancer (LC), new research by the Oregon Health and Science University suggests. As published in the 16th February online edition of the Journal of Clinical Oncology (10.1200/JCO.2009.25.9739), women aged 50 to 76 years who take oestrogen plus progestin (O+P) may have an increased risk of the disease.

According to the researchers, although the risk is duration-dependent, with women taking HRT for ten or more years at greatest risk of developing LC, an acceptable length of HRT has yet to be determined. However, it was noted that while the risk of developing LC for women using O+P for ten years or longer was approximately 50 per cent more than women not using HRT, this risk is small compared to the risk from smoking.

The scientists reviewed data collected from 2000 to 2002, and identified 36,588 peri- and postmenopausal participants aged 50 to 76 years who met their study criteria and followed them for six years. At the end of the observation period, December 2007, 344 of the participants had developed LC. After adjusting for smoking, age and other factors that affect the risk of the disease, the researchers determined that the use of O+P for ten or more years was associated with an increased risk for LC, compared with no use of HRT. They also found that the duration of use was associated with an advanced stage of cancer at diagnosis.

This research is not the first to highlight the risk of HRT use with LC. Scientists from the University of California, Los Angeles Medical Center previously reported that HRT using O+P increases the risk of death from LC. After the eight-year total follow-up from the study, published in the 20th September 2009 online edition of The Lancet (10.1016/S0140-6736(09)61526-9), the researchers found that more women died from LC in the combined HRT group than in the placebo group (73 compared to 40 deaths). In other words, women in the HRT group were 71 per cent more likely to die.

Further, it is not just an increased risk of LC that has been linked with HRT. According to results from a Stanford University study, published in the 5th February 2009 edition of the NEJM (2009;360:573-587), postmenopausal women who take combined O+P menopausal hormone therapy for at least five years double their annual risk of breast cancer. This multi-centre study also found that women on HRT can quickly reduce their risks of cancer simply by stopping the therapy.

Research such as this suggests that postmenopausal women, especially current smokers or long-term past smokers, should carefully consider these risks before initiating or continuing combined O+P use.

Alice Rossiter
Editor, Cancer Drug News

Monday, March 1, 2010

Scientists establish link between deprivation and poor prognosis for BC

Deprivation has long been known to play a role in the development of a wide range of diseases, and to a higher risk of recurrence or death for patients diagnosed with a number of cancers. Previously, the effect of material deprivation on cancer survival in England and Wales was measured by Cancer Research UK, and results showed that cancer survival for adults is generally lower among patients in more deprived groups, even after allowance is made for the higher mortality from all causes of death in these groups.

The reasons for survival rates differing between breast cancer (BC) sufferers from poorer areas and more affluent areas has never been fully understood. Now, researchers from the University of Dundee have established a link between deprivation and the p53 gene, which explains why women from poorer backgrounds are less likely to survive BC. The team identified, for the first time, that p53 mutation in BC is associated with socio-economic deprivation, and that this helps account for the poorer prognosis for women from deprived communities.

As detailed in the 26th January online edition of the British Journal of Cancer (10.1038/sj.bjc.6605540), the scientists found that women from deprived backgrounds were more likely to experience a mutation of p53, and that this linked to higher relapse and mortality rates. According to the team, there are two ways that p53 mutations can come about; one is as a result of genetic predisposition and the other is as a result of lifestyle. Smoking, drinking and poor diet can lead to p53 mutations, and are more common in women from lower socio-economic groups, who are also more likely to experience a recurrence of the disease and to die as a result of BC.

The survey looked at a total of 246 women who underwent treatment for BC between 1997 and 2001. Examining frozen tissue, tests were carried out to determine p53 mutation status. Using the patients' postcodes, a deprivation score was attributed to each and examined against the outcome (full recovery, relapse, death). The team found that patients in the lowest socio-economic group were significantly more likely to have a relapse and die compared to those in more affluent categories. They also demonstrated that the worse survival and shorter disease-free interval in BC for the most deprived patients is associated with tumour p53 mutation.

This research demonstrates a strong link between p53 and deprivation, and then between p53 mutation and recurrence and death. The social application of this work would suggest that if deprivation can be targeted, then the deprived population would be less likely to have problems with their p53 gene and go on to develop BC. In reality, this is unlikely to be achieved, however, there has been numerous work surrounding the p53 protein: Cyclacel Pharmaceuticals' seliciclib (CYC202) is a promising anticancer agent that promotes cancer cell death by downregulation of key proteins, such as p53 and Mcl-1, associated with survival of cancer cells; and new research by Dartmouth Medical School has shown that p53 limits the growth of cells with incorrect numbers of chromosomes and prevents their progression toward cancer.

Alice Rossiter
Editor, Cancer Drug News