Gender Specific Oncology

11 Aug 2009

Some of the most prevalent cancers are those that are specific to – or, in the case of breast cancer, almost specific to – one or other of the genders.

In all developed countries, the breast and prostate are among the four most common cancer sites, and testicular, cervical, ovarian and uterine cancers are also relatively frequent.

The options available for early detection and treatment of many gender-specific cancers have expanded greatly in recent years, but there are still unmet medical needs associated with them.

A meeting in London in early July brought together academic and industrial experts from across the UK to discuss new developments in the prevention, detection, diagnosis and treatment of these cancers. It was organised through LTN (, a not-for-profit organisation set up in 2001 to facilitate knowledge transfer between academia and industry in the Greater South East of England with the aim of driving down the time, cost and risk of bringing new technologies to the market.

A large and disparate audience of researchers heard four presentations describing novel interventions at all stages of the gender-specific “cancer journey”, from prevention all the way through to the long-term follow-up of cancer survivors.

Karin Hardt from GSK Biologicals, based in Belgium, gave an overview of the development of the CervarixTM vaccine for the prevention of cervical cancer. Infection with an oncogenic variant of the Human Papilloma Virus (HPV) is necessary but not sufficient for the development of cervical cancer. It is thought that 50-80% of sexually active women will acquire HPV infection during their lifetime, and that half of these infections will be oncogenic. Although cervical screening, which can detect most cases of this cancer at a stage where it is extremely easily dealt with, is widely available at least in developed countries, more than 250,000 women die from this disease each year. GSK has developed CervarixTM to protect against the two HPV genotypes, 16 and 18, that are most frequently found in cervical cancer cases. A recently published Phase III clinical trial of this vaccine (Paavonen et al. (2009), Lancet, epub ahead of print) has concluded that it is highly effective in protecting women against developing pre-cancerous cervical lesions associated with HPV-16/18, and that serious adverse effects are rare. The vaccine offers some limited cross-protection against other oncogenic HPV strains. Hardt and her colleagues are seeking academic collaboration for further extensive clinical trials.

Most breast cancers are sporadic, but a small minority are associated with mutations in single genes, particularly the breast cancer susceptibility genes BRCA1 and BRCA2. Although most women who carry one of these mutations will develop breast cancer before old age, these are relatively rare mutations and only account for about 3% of cases of breast cancer. Ascertaining the BRCA status of all women with breast cancer is important not only because of its implications for the patients’ families, but also because tumours with BRCA mutations have specific molecular characteristics that affect the prognosis and optimum treatment of the disease. It is not always possible to predict hereditary cancers from family history, and genotyping is expensive. Speaker Diana Eccles from the University of Southampton is involved in the POSH study, surveying genotypes, phenotypes and outcomes in UK breast cancer patients diagnosed under the age of 40. A higher proportion of cancers detected in these younger women will be hereditary. Eccles and colleagues have been using a novel technique, array comparative genomic hybridisation (array CGH) to discover areas of differential DNA amplification in breast cancers from women with known BRCA1 and BRCA2 mutations compared with young women from the POSH cohort with sporadic breast cancers. Combined with more conventional immunohistochemical profiling of tumours, the novel tumour based tests are being used to predict the risk of an individual young breast cancer patient having a BRCA mutation, with only high-risk women then going forward for genotyping. The group is now investigating the patenting of their array CGH test.

The other presentations covered recent developments in male specific cancers. Testicular cancer is one of the most readily curable of all cancer types, with a five-year survival rate approaching 98%. Many patients are cured through surgery only, but the relapse rate is lower if adjuvant radiotherapy or chemotherapy is used. However, with patients now typically living for decades after recovery, it is important to consider the effect that this quite aggressive treatment can have on the later health of cancer survivors. Thomas Powles of St. Bartholomew’s Hospital, London, has followed up records from testicular cancer patients for decades. He has found that they are at higher risk of second cancers and some other diseases, such as heart disease, than men with no previous history of cancer, and that adjuvant treatment increases this long-term risk. He has also been looking at men whose testicular cancer has relapsed, and whose long-term outlook can be quite poor, using molecular markers and simple demographic characteristics to classify them into groups with good, intermediate and poor prognosis. “If we can identify men with a poor prognosis, we can target them with more aggressive therapy”, he says.

Prostate cancer is the most common of the male-specific cancers, and is also often curable or at least controllable, particularly in older men. It is almost always amenable to hormonal manipulation and, in the later stages, to targeted therapies, including chemotherapy: most pharmaceutical company have a drug discovery programme in this area. The proliferation of prostate cancer cells is stimulated by the action of the androgen receptor which in normal men, and in early cancer, is controlled by testosterone. Many drugs in clinical use, such as AstraZeneca’s Casodex and Zoladex, act by inhibiting the production or the activity of testosterone. These drugs, however, are not active if androgen receptors become independent of testosterone, as often happens in the later stages of the disease. For these cases, too, the widely used biomarker PSA (prostate specific antigen) is no longer as useful a predictor of disease status as in early cancer. Don Newling, senior clinical research physician at Astra Zeneca in Alderley Park in Cheshire, UK, is studying mutations in the androgen receptor that lead to its becoming testosterone-independent and, by the accepted definition, oncogenic. “The androgen receptor has a pivotal role in all prostate cancers. We are hoping to develop drugs that target it directly, and, therefore, will be active against all types and stages of this cancer”, he says.

The meeting ended with a networking lunch and a poster session, in which universities from London and the greater South-East region showcased fourteen innovative technologies that could help diagnose and treat these and other gender-specific cancers.