Are Gene-Sequencing Assays Worth It?

At the San Antonio Breast Cancer Symposium in December, I picked up a flyer from Los Angeles-based City of Hope Medical Center's Clinical Molecular Diagnostic Laboratory. It reads: Coming soon ... Next-Gen Sequencing Panels. The photocopied sheet of white paper then listed the panels, their individual genes, and the cost of the gene panel:

*Onco-44-gene panel, $1,875
*Cancer-30-gene panel, $3,250
*Breast-17-gene panel, $2,350 (ATM, AXIN2, BAP1, BARD1, BRIP1, CDH1, CHEK2, MRE11A, NBN, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53, XRCC2)
*Ovarian-22-gene panel, $2,350
*Colorectal-19-gene panel, $2,350
*Cancer-428-gene panel, $3,950

I've been skeptical about the new wave of tumor profiling in breast cancer, and that seems to revolve around its lack of clinical relevancy. But such services are tempting for women like me who have metastatic breast cancer. They make me feel that the answer is out there now in a genetic profile.

Last year, several posts on a breast cancer support group message board of which I'm a member discussed specific laboratories that can perform assays, or tests, to reveal which chemotherapy drug would work best. As a result, during a Q&A at a local breast cancer meeting, I asked a top breast cancer oncologist at Memorial Sloan Kettering Cancer Center. He said it was "fraud." I was shocked, as I didn't expect that kind of an answer. I thought I would get the scoop, and was disappointed at his choice of such a strong, finite word. But that word clearly conveyed his thoughts on the topic.

Genetic assays often provide more data than we know what to do with. Yet the services offered by laboratories sometimes make us feel that getting our tumors gene sequenced today is the answer. More to the point – and something that often escapes us – many of these assays are not clinically relevant at this time: They don't translate from the bench to the clinic. So, are we raising our hopes and at the same time wasting our time and money? Are these assays just another way for laboratories to make additional money by giving us information that is not yet useful clinically? Gene sequencing is not new, but lately it's become much cheaper than previously and has resulted in an avalanche of data.

Besides relevancy, another important word is diagnostics. Put simply, for breast cancer: ER/PR, HER2. Assays show us which breast cancer subtype we have and therefore which supplemental treatments work best, which means that a specific diagnostic test corresponds with specific drugs, such as Tamoxifen, Femara, Herceptin, and Tykerb. Further, for some women with early stage breast cancer, Oncotype DX is another clinically relevant assay that helps patients and oncologists make additional informed decisions about appropriate treatment. This 21-gene assay and its recurrence score are a way for us to determine whether adding chemotherapy to endocrine therapy would likely be beneficial (except of course for the patients who fall in the middle of the scale, and perhaps the results of the TAILORx trial will eventually result in tweaking the assay and developing a second-generation Oncotype DX).

As a breast cancer advocate, these are the types of questions that I try to keep in mind before I get caught up in the hype of genetic profiling. But I'm optimistic that the genetic quagmire of such sequencing will some day be the antithesis to the Pandora's Box of cancer that it has opened and will provide more clinically useful answers.



Joan is a helpline volunteer, member of SHARE Leaders, and a consumer reviewer at the Department of Defense Breast Cancer Research Program. She also facilitates SHARE's metastatic breast cancer support group, Living with Uncertainty.