December 9, 2022  Print

A recent study published in Nature Genetics has shed light on some of the factors that influence long-term survival following a diagnosis of ovarian cancer.

High-grade serous ovarian cancer is the most common form of ovarian cancer and is often fatal.  Fewer than 15% of women with this disease survive more than 10 years following diagnosis.  Those who do survive more than 10 years are known as “exceptional survivors”.

The study was part of a US Department of Defense (DOD) Ovarian Cancer Research Program (OCRP) initiative, with collaborators in the US, UK, Canada and Australia. This included a team led by Professor Anna DeFazio at The Westmead Institute for Medical Research.

Professor DeFazio says, “The study analysed 60 patients with advanced-stage, high-grade serous ovarian cancer who survived more than 10 years after their initial diagnosis.

“The research teams compared the primary tumour samples of these 60 exceptional survivors with similar samples from people with more typical outcomes, including those with short (less than 2 years) or moderate-term (2-10 years) survival.

“To do this, we used whole-genome sequencing, transcriptome profiling (studying which sets of genes are expressed) and methylome profiling (studying why genes are expressed at a particular level), as well as examining the patients’ clinical histories.”

A few factors were identified as potentially influencing long-term survival following diagnosis. These include:
  • Long-term survivors were more likely to have several alterations in genes that are associated with DNA repair. These alterations could make them highly sensitive to chemotherapy, or reduce the likelihood of developing drug resistance
  • Long-term survivors had more frequent cellular variations, resulting in enhanced immune responses.

The study also identified that patients with BRCA1-altered tumours (a feature normally associated with favourable chemotherapy outcomes) fell into three groups. Interestingly, one group had an unusually poor survival rate.

Professor DeFazio says, “An unanticipated finding was that the patients in this group with unusually poor survival rates showed signs of exposure consistent with a history of tobacco consumption. 

“Little is known about the influencing factors when it comes to long-term survival following a diagnosis of high-grade serous ovarian cancer. So, this is a significant finding because smoking is a modifiable lifestyle factor that could have an adverse impact on survival outcomes for patients with BRCA1 alterations.

“Learning more about how the immune system impacts on treatment response and long-term survival may provide clues on how to best use immunotherapy for ovarian cancer, an area that has been very challenging so far, and needs more research.”