A Geneticist's Take on Cheaper Tests for Breast and Ovarian Cancer Risk

A startup in Burlingame, California called Color Genomics is offering a genetic test for breast and ovarian cancer risk for only $249. Despite the relatively low cost, you’ll get a lot for your money.

The test looks at every base pair of 19 different genes including the two made famous by Angeline Jolie, BRCA1 and BRCA2. Other tests like this that are currently on the market cost much more out of pocket ($2000 or more).  And companies that look at only the most common differences that are at a similar price point would miss rare ones.

For example, the older version of 23andMe looked at only the three most common variants in BRCA1 and BRCA2 genes. (To be fair this is back when Myriad owned the rights to BRCA1 and BRCA2 and so companies were constrained in what they could offer.)

Promethease, an online site that converts ancestry data from either 23andMe or AncestryDNA into health and trait related data, gives you many more SNPs for BRCA1, BRCA2, and many other genes involved in breast cancer (and most every other disease or trait). But still, it and services like it can only see what they are looking for. There is no chance of finding rare changes not already included in the subset of DNA they analyze.

So this test sounds great—lots of data for very little money. Of course there are tradeoffs in everything.

A potential downside of sequencing entire genes is that you end up with too much of a good thing. You will probably find DNA differences in your gene(s) never before seen in anyone else who has been tested. They could be trouble, mean nothing, or be somewhere in between. (Heck they might even be helpful!)

Color Genomics deals with this potential problem in at least a couple of different ways. One is to come out and say that you are going to see some of these things and they don’t know what they mean. The other way is to provide genetic counseling as part of the service.

We will see if these are good enough to help patients deal with this much data. And hopefully they are.

The company plans to offer up any new variants they find in an anonymized form to ClinVar, a public database for this kind of information. This has the real potential to discover new variants that increase a woman’s risk for breast and ovarian cancer. And the more women (and men) tested, the more variants they’ll find.

Add to this the fact they plan to sponsor testing of women who can’t afford the test and that they want to study populations other than the ones of European descent normally studied and you have what looks like a win-win for the company, the customer and, to some extent, society. But of course, nothing is perfect…

Testing Too Many Women?

A key benefit and concern with this sort of testing is that many women without a family history of early breast and/or ovarian cancer will get tested. On the one hand this sort of testing can help women who for one reason or another have no family history of breast or ovarian cancer (adoption, BRCA mutation passed through the paternal line, etc.). As seen here, women without a family history can still have BRCA1 variants that can lead to an increased risk for breast or ovarian cancer.

The flip side of this is the test may find women with known variants that may not be as dangerous as they think. In the general population, a woman has about a 12% chance of developing breast cancer and a 1.3% chance of developing ovarian cancer in her lifetime. With certain BRCA1 variants, the risk for breast cancer goes up to between 37% and 85% and the risk for ovarian cancer goes up to between 16% and 60%. This is lower than the older values you may have heard before.

From the wide range of risk, you can probably tell that the risk for developing breast cancer is not the same in different women with the same BRCA1 variants. The environment, each woman’s genetic background and a host of other factors all influence her chances for developing breast and/or ovarian cancer.

So this brings up the question of what a woman should do if she has a BRCA1 difference known to increase her risk for breast and ovarian cancer. The best treatment almost certainly depends on where she is within the range of risk but without family history, it is very hard to pin down her actual risk as opposed to her average risk.

Now none of this means women should not be tested. What it does mean is that how the data is presented to the customer is critical so she can make a truly informed decision based on her results. Genetic counseling will definitely help as well but the customer also needs to have a pretty solid understanding of what these risk numbers mean.

This also shows a bit why breast and ovarian cancer is such a tricky business. If someone came out with a similar sort of test for type 2 diabetes (which no one will soon), the treatment might be something simple like exercise more and eat less sugar. In this case, even if the risk was overblown, the remedy wouldn’t be so bad. If anything, the customer ends up healthier!

The same is obviously not true for removing one’s breasts and/or ovaries. This is a permanent treatment.

Less Revolutionary, More Evolutionary

Having said all of this, overall the test looks to be as good as a test like this can be at this time. It has the usual set of problems like making sure customers understand that a negative result does not mean they aren’t necessarily at an increased risk of breast or ovarian cancer and that a positive result does not mean they will for sure get cancer. But the company appears to be dealing with these issues pretty well.

The test has to be ordered by a doctor (although it sounds like they have some doctors lined up ready to order a kit for the customers) and the company gives complementary genetic counseling. This seems to be a great way to get genetic testing like this to as many people as possible.

In fact, the test really is a step back from the sort of testing 23andMe offered. Their testing was revolutionary—here is everything we know about all the DNA we look at, you don’t need a doctor to get the results, and you don’t need a genetic counselor to help interpret. This was so revolutionary that part of their service ended up getting shut down by the FDA.

The test offered by Color Genomics is really more evolutionary. A simpler, cheaper way to get testing in a way that is just a bit different than the old way of doing it. It looks like Color Genomics learned some key lessons from 23andMe’s experiences. And this is a good thing for people who want to be tested.

A video showing unintended consequences of genetic tests