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Special populations: People considering genetic testing
A recent New York Times report discussed how genetic testing could provide “grim data” without guidance for patients. While this is a valid concern, this report does not sufficiently emphasize certain important issues regarding genetic testing, particularly the need for genetic counseling by a health care provider with expertise in genetics before and after genetic testing. (4/5/16)
A patient’s story about how genetic testing offered more confusion than answers was the topic of the New York Times (NYT) report, “When Gene Tests for Breast Cancer Reveal Grim Data but No Guidance.” This report discusses two types of genetic testing: germline testing that looks for mutations in genes that increase cancer risk, and direct sequencing of tumor DNA to look for mutations in the tumor, which might help to optimize treatment.
The report begins with the story of a patient who had germline genetic testing, and was found to have a variation of unknown significance (VUS) in an unspecified gene, which led to confusion about the most appropriate treatment for her. The report then discusses how sequencing DNA from breast cancer tumors usually provides few answers for patients.
While these are valid concerns, this report raises many unaddressed issues. Nor were the ambiguous/troublesome cases in the report counterbalanced by stories of people who benefited from either germline or tumor genetic testing.
According to the report, the patient was about to begin radiation therapy after a lumpectomy for breast cancer. Her physician, a radiation oncologist, told her that, “A genetic test showed she had inherited an alteration in a gene needed to repair DNA. Radiation breaks DNA, so the treatment might actually spur the growth of her cancer.” The report also stated that the “surgeon urged her to not take the risk, and to have a double mastectomy instead.”
“But patients need to be prepared for ambiguities [regarding genetic testing results]. “Typically they are not,” said an oncologist.
After the discussion with her radiation oncologist, the patient consulted with a medical geneticist, who told her that the mutation she had was not known to be harmful and recommended that she go ahead with the radiation therapy.
The report notes that the patient carried a variation of unknown significance (VUS) in an unspecified gene. The report stated that, “Having a variation of unknown significance means it does not destroy the gene’s function, but may alter it—leaving the implications entirely uncertain.”
Genetic testing does not offer clear-cut answers for everyone.
This report switches between germline testing and breast cancer tumor gene testing without fully explaining the difference between the two.
“Yet now, as powerful new precision medicine drugs elicit striking responses in patients with other cancers—lung, colon, melanoma, blood, gastric—metastatic breast cancer patients have been left out.”
This statement implies that there are no precision drugs for metastatic breast cancer patients. While none are currently approved, clinical trials are ongoing for PARP inhibitors, a type of targeted therapy for men and women with both metastatic breast cancer and an inherited BRCA mutation. In addition, open clinical trials are looking at genetic changes in tumors from people with metastatic breast cancer. Such trials are the first step in bringing FDA-approved precision drugs to people with metastatic breast cancer.
Summary: “When Gene Tests for Breast Cancer Reveal Grim Data but No Guidance.”
Despite the shortcomings of this report, it does raise a valid concern: genetic testing can give patients and their health care providers access to lots of information about their inherited gene mutations and the genetic changes that occurred in their tumors. Not all of that information is associated with guidelines for care or treatment, however, and we still have much to learn about how to best interpret and use genetic information. Researchers have access to more genetic data than ever before, and it is a new and exciting time in the world of genetics! But in some cases, we are stepping into uncharted territory, and there will undoubtedly be ambiguities and unknowns. Researchers learn more every day to help healthcare providers provide clearer guidance to patients. Patients need to be told that sometimes genetic testing will give them results that are associated with guidelines for risk management and treatment, but there is a possibility that the test result will not provide clear answers.
Today, when a woman finds that she is a BRCA mutation carrier, she is put on a cancer screening regimen and is educated on all of her preventative care options. Expert guidelines identify how health care providers should care for BRCA mutation carriers—this wasn’t the case when BRCA was discovered in the early 1990s. That doesn’t mean that testing wasn’t worthwhile back then; it was just more confusing than it is today. Today we have care guidelines for Lynch Syndrome patients, PTEN mutation carriers, TP53 mutation carriers and others. Understanding how to care for all of these patients did not happen overnight.
Researchers and healthcare providers will undoubtedly understand more about these variations of unknown significance in the future, and additional treatments will be developed to target more tumor mutations. Today, patients should know that they may have ambiguous test results, and to consider whether or not they want to get genetic testing in the face of this possibility. But, the ambiguity is only one side of this story. Genetic testing regularly provides very important and helpful information to patients. While genetic testing may not always provide clear guidance, it often does, and that should not be downplayed. The bottom line is that it should be pursued in conjunction with experts who are familiar with the nuances of testing so that results can provide maximal benefit to patients.
Kolata, G. “When Gene Tests for Breast Cancer Reveal Grim Data but No Guidance.” The New York Times. Published on March 11, 2016.
Bernier, J. and Poortmans, P. “Clinical Relevance of Normal and Tumour Cell Radiosensitivity in BRCA1/BRCA2 mutation carriers: A review.” The Breast. 24(2); p.100-106, April 2015.
Other organizations have commented on this report as well:
Forman, A. and Daly MB. “Genetic Testing May Give Answers, But May Also Leave Questions.” Fox Chase Cancer Center. Published on March 14, 2016.
Mercier, A. and Goldman, E. “When Gene Tests for Breast Cancer Reveal Grim Data but no Guidance.” Jewish Genetics. Published on March 21, 2016.
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