February 23, 2012

expert reaction to study of breast cancer genetics as published in The Journal of Pathology

The Journal of Pathology published a study which suggested three new genes implicated in breast cancer cells and sequenced the DNA of two breast cancers caused by a faulty BRCA1 gene.

Dr Paul Pharoah, Reader in Cancer Epidemiology, University of Cambridge, said:

“The top line of the news release from Breast Cancer Action overstates the case. To state that the genetic code of hereditary breast cancer has been unravelled for the first time is inappropriate, for the following reasons.

“The general public (and many scientists) equate ‘genetics’ with inherited genetics/inherited disease risk. Cancer genetics can either be about inherited disease risk – which is enormously interesting to the public – or about the fundamental biology of cancer, which, if it has no immediate clinical implications, is much less interesting. The fundamental biology side involves studying the multiple genetic mutations that are not inherited but that cancer cells acquire during a person lifetime. Understanding these acquired mutations and how they lead to cancer is important and may ultimately lead to better treatment – but it is important to note that these mutations have not been inherited.

“Juxtaposing the term ‘genetic code’ with discussion of hereditary breast cancer creates the erroneous impression that the three genes identified may have something to do with inherited genetics. It thus makes it appear to be a story of great interest to the general public.
“The fact is that this is a story about somatic genetics. In particular it is about the somatic genetics of breast cancer that has occurred in women who have an inherited gene defect and were at high risk of developing cancer. It has identified three genes that are faulty in breast cancer cells, but may or may not be important in affecting the behaviour of these cells. This may or may not lead to the development of better treatments for this specific type of cancer.

“There are no immediate clinical implications of these findings.

“Hereditary breast cancer DOES NOT account for 10% of all breast cancer. This is an oft-quoted number that is fundamentally wrong. A small proportion of the population are at very high risk of breast cancer because they have inherited a fault in one of a handful of genes (mainly BRCA1 and BRCA2; incidentally, the estimated lifetime risk of breast cancer in the average woman with an inherited fault in BRCA1 is 65% not 85%). Inherited faults in these genes account for less than 5% of all breast cancers. However, all breast cancer is more or less inherited – a woman’s genetic make-up will put her at a greater of lesser risk of breast cancer on a continuum of risk.

“If this paper was as important as the release implies, I would expect it to be published in a higher profile journal.”

‘A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor-negative and -positive breast cancers’ by Rachael Natrajan et al., published in The Journal of Pathology on Friday 24th February