Why is ovarian cancer different?

Unlocking ovarian cancer heterogeneity: advancing immunotherapy through single-cell transcriptomics

https://tinyurl.com/2vpf36vp

Gradually the reasons why ovarian cancer is such a difficult challenge to treat, with high mortality, are becoming clear. This article uses new technology; single cell RNA sequencing to show the variation in the immune features of the individual cells, which make up ovarian cancer.

It is well known that ovarian cancer has great capacity to resist immunological challenge. Tumour micro-environments exist with protective features involving white cells and suppressor cells which enable cancer survival and progression.

Single cell sequencing reveals targets for new treatment such as check-point blockade, (which is important with mis-match DNA repair). Also, the new information may identify those women who will have a less effective response to standard treatment.

No longer number 1

Disparities in ovarian and uterine cancer in relation to the development of novel therapeutics. 

https://tinyurl.com/249mzrma

Ovarian cancer has always been shown to be the gynaecological cancer most likely to cause death. With the onset of targeted therapy, this no longer appears to be the case. As this article shows it is now more likely that women in the US will die of uterine cancer.

The number of deaths from ovarian and uterine cancer were compared for the periods 2001-2019, and 2015-2024, with estimated mortality for the latter period. During this time ovarian cancer deaths decreased by 1.1% per annum, and uterine cancer deaths increased by 3%.

Total numbers of deaths per annum for ovarian cancer at about 12750, are less in 2024 than for uterine cancer, being 13250. This is a reversal of previous ratios of 1.4 to 1. 

It is speculated that this change is due to improved treatment for ovarian cancer. New targets for personalised treatment have led to much interest by pharmaceutical companies in developing potentially highly profitable new treatments. Clinical trials of treatment of ovarian cancer are four times the number of those for uterine cancer. Uterine cancer is common for black women. This too is a thought to be a factor for the disparity in clinical trials.

The Viking Gene

Two founder variants account for 90% of pathogenic BRCA alleles in Orkney and Shetland

https://tinyurl.com/54pbt2jh

For most women, the chance of carrying the BRCA gene mutation is 1:400. In certain populations, notably the Ashkenazi Jews, Scandinavians from Norway, and the Shetlanders this risk increases to 1:40, making breast, ovarian and other cancers ten times more likely.

With next generation gene sequencing, it is now possible to identify variants of the BRCA genes which are responsible for this increased risk. Using genealogy, the origins of the mutations can be traced to a founder variant. 

Founder effect is increased when populations are small, with in-breeding. In Norway this followed the ravages of the bubonic plague, for the Ashkenazi the outside stimulus was the destruction of Jerusalem. Recent research has identified the founder family in the Shetlands as settlers on the island of Whalsay before 1750. Knowing the BRCA variant means that whole of population screening can be done more cheaply.

Too much of a good thing?

Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention

https://tinyurl.com/5hb76d25

Pre-natal testing has become normal for all pregnant women in first world countries. With the availability of cheaper genetic testing, it may be possible to detect potentially lethal genetic mutations for mothers as well as the infant.

BRCA1/2 mutations are found in 1 in 400 women, these mutations increase the risk of breast, ovarian and other cancers. Early intervention has proved effective for prevention of cancer development for these women.

This study looks at the theoretical cost versus the benefit of doing prenatal testing and subsequent risk reduction. Retrospective analysis of almost 1.5 million women who had genetic screening for obstetric care suggested that, if BRCA1/2 and other autosomal dominant genetic mutations were included in the screen, there would be significant reduction in cancer.

However, whether the benefit of early knowledge of potential risk outweighs the adverse effects of increased anxiety, problems with employment and insurance, together with the reduced quality of life is not addressed. There is a cost-benefit advantage in terms of healthcare costs but there is a bigger picture.