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Expert Discusses Genomic Testing in Breast Cancer

Monday, August 28, 2017
However, in that study, researchers looked at breast cancer and other types of cancers. In mostly breast cancer with HER2mutations without HER2 genome implication, they saw responses to Nerlynx. Not all mutations are the same, and not all mutations have the similar results in all tumor types as we may have thought. 

PI3K is another interesting gene where mutations have been associated with a better prognosis in breast cancer. The question is, “Can we use them to predict response to PI3K inhibitors or mTOR inhibitors?” To date, the data are inconclusive.

Another thought is the estrogen receptor (ER) mutations that may predict responses to different types of endocrine therapies, such as Faslodex (fulvestrant) compared with aromatase inhibitors. There are studies also looking at Faslodex versus CDK 4/6 inhibitors, such as Ibrance (palbociclib), suggesting that they do not predict [responses with] CDK 4/6 inhibitors, but they may be predictive of response to some of the basic endocrine therapies. 

That research applies more to the liquid biopsies where we have been able to find mutations in circulating-free DNA in the plasma, which may be predictive but it is still an area of investigation. 

What are the current guidelines for genetic testing?

In patients with metastatic breast cancer, the biomarkers we always test for are ER, HER2 and perhaps BRCA. Now, since we are more interested in identifying BRCA mutations, it is standard of care — or at least recommended by national guidelines — to sequence the BRCA1/2 genes in patients with triple-negative breast cancer in which the ER, progesterone receptor, and HER2 tests are negative.

Next-generation sequencing, meaning sequencing an entire tumor, is not recommended as a standard of care yet. It is done whenever possible, and especially at the major academic institutions, with the goal being to direct those patients to clinical trials—single-institution trials, big institutions, and also the National Cancer Institute (NCI) MATCH trial, for example. This is where there are more than 20 arms depending on the mutations identified, so patients may be directed to those trials. 
The NCI-MATCH trial screened about 10,000 patients with metastatic cancer of many types and they closed the screening step. Now, they are only allowing patients to enter those trials if sequencing is done by different laboratories. 

How are these genomic tests personalized for patients?

For patients with metastatic breast cancer, those tests are relatively easily accessible and available. There are many companies now where you can send them the tissue or the plasma, and they can look for mutations in the tissue or mutations in circulating-free DNA in the plasma. The question is, “What do you do with that information to be able to personalize these therapies?” That goes into the area of clinical utilities. Technology is ahead of the clinical utility of personalized medicine. We can identify mutations in tumors or in the plasma, but what we do with that information is not clear. That is why it is important to continue to use clinical trials. 

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