Sunday, November 4, 2012

A small step forward in familial breast cancer

Many years ago I took care of Sally, a close friend who was discovered to have breast cancer. Many of the women in her family had also been diagnosed with this disease, so her diagnosis was no surprise. Nor was the fact that we found early precancerous changes in her “normal” breast. For most of us caring for Sally, it was clear that we should not only recommend a mastectomy in her cancerous breast, but also in the other “precancerous” one. For us, it was not a matter of “if” but “when”. This all happened many years ago, before the discovery of the BRCA1 and BRCA 2 gene mutations that account for about 5%, maybe 10% of all breast cancer cases. But when Sally was tested for these mutations, years after her treatment, she had neither. It turns out that only about one-fourth of women with a strong family history of breast cancer have this mutation. The others don’t. What they do have is multiple small changes in genes that seem to predispose them to breast cancer. The big question is how do we find these women. This is important to know because many women faced with a high risk of breast cancer can undergo more intensive screening, preventive hormone treatment or even prophylactic mastectomy. And even more important, perhaps, is that women without the risk can avoid all this. Now a group in Australia has isolated a cluster of 22 genetic changes called SNPs that mark for a higher risk of breast cancer in affected families. The results were published in the October 29 issue of the Journal of Clinical Oncology. SNPs mean that there is a slight change in a gene that normally would not be noticed and usually causes no problems. But this array of 22 genes seems to be important. Women with these changes had a higher risk of breast cancer, particularly at a very young age, younger than 35, an age when we rarely screen. Still, the test isn’t that predictive. Although the risk of developing breast cancer in these younger women with the abnormal gene cluster was over three times normal, because the risk in this age group is so low, this didn’t translate into a lot of cancers. For older women, the risk was doubled. So, it is unlikely that women with these somewhat higher risks would opt for anything but more careful surveillance – keeping up their mammography, perhaps more often. There are two messages, though, to take away. One is that if a woman is in a family with high breast cancer risk and doesn’t have the abnormal genes, she can breathe a little easier and worry less. The other message, for me at least, is that we are entering into a new era of genomic medicine. Our ability to find abnormal genes in people with diseases is increasing exponentially and perhaps within a few years, we will be able to more accurately predict who will and will not develop a particular disease, in this instance, breast cancer.

2 comments:

Greg Pawelski said...

The human genome is comprised of more than 23,000 genes: Splice variants, duplications, mutations, SNPs, non-coding DNA, small interfering RNAs and a wealth of downstream events, which make the interpretation of genomic data highly problematic. The fact that a laboratory can identify a gene does not confer a certainty that the gene or mutation or splice variant will confer an outcome. To put it simply, the input of possibilities overwhelms the capacity of the test to rule in or out, the answer.

Susan R Wing said...

Cancer is termed deadly disease which happens due to uncontrollable cell growth which keep on multiplying and do not die. This uncontrollable cell growth leads to formation of tumor. There are more then 200 types of cancer a human can face. Cancer can be cured only when diagnosed in earlier stages.