Breast cancer: More pathogenic variants detected as multiple-gene sequencing takes over

 

The introduction of multiple-gene sequencing led to a substantial increase in detection of pathogenic variants in a study of women with breast cancer treated in community practice, results of one retrospective study show.

Multiple-gene sequencing rapidly replaced BRCA1/2 only testing over a 2-year period in the study, driven in part by technological advances and regulatory changes that made comprehensive low-cost genetic testing more accessible, investigators wrote. The report was published in JAMA Oncology.

That quick uptake increased detection of genetic variants that could change care, with no associated increase in prophylactic mastectomy over that same time period, said Allison W. Kurian, MD, of Stanford (Calif.) University, and her coinvestigators.

“The greater yield of clinically relevant information with multiple-gene sequencing offers a major potential advantage over more limited BRCA1/2-only tests,” noted Dr. Kurian and her colleagues.

Their analysis included 5,026 women with stage 0-II breast cancer diagnosed from January 2013 to December 2015 and enrolled in the Individualized Cancer Care (iCan Care) study. That study started enrolling 1 month before a U.S. Supreme Court decision on gene patents, which led to lower costs for multiple-gene sequencing tests for breast cancer risk, Dr. Kurian and her coinvestigators said.

Overall, about one-quarter of women in the study had genetic testing, and that did not change over time. What did change over time was the number of women undergoing multiple-gene testing: In 2013, only 25.6% underwent multiple-gene sequencing, versus 74.4% for BRCA1/2-only testing; by 2015, those figures flipped to 66.5% and 33.5%, respectively.

Multiple-gene sequencing increased detection of pathogenic variants in women at average pretest risk (4.2% versus 2.2% for BRCA1/2-only testing), according to the reported data. Detection was increased in women at high pretest risk due to young age, triple-negative breast cancer, or other factors (12% versus 7.8%).

 

Prophylactic mastectomy was most strongly associated with detection of pathogenic BRCA1/2 variants, according to Dr. Kurian and her coinvestigators. More women with those variants strongly considered the procedure and had it recommended by their surgeons, and ultimately, significantly more underwent the procedure (79.0% versus 37.6% for other pathogenic variants; P less than .001).

While those mastectomy outcomes were reassuring, Dr. Kurian and her colleagues said, their research uncovered two “important limitations” to multiple-gene sequencing that should be addressed.

They found that testing was done post surgically in 32.5% of women who had multiple-gene sequencing, compared with 19.9% of women who had BRCA1/2-only testing. Postsurgical testing is “too late” and limits its use to make decisions about surgical prevention of second cancers, they said.

They also found racial disparities in detection of variants of unknown significance (VUS). In particular, VUS were detected in 23.7% of white patients, compared with 44.5% of black patients and 50.9% of Asian patients. That’s because most of the genes were first sequenced in white patients, the investigators noted.

 

In previous experience with BRCA1/2 testing, extensive VUS reclassification occurred after broader testing within the population over 2 decades.

“It is a crucial priority to resolve persistent racial/ethnic disparities in genetic information, particularly as increasingly comprehensive sequencing tests enter clinical practice,” the investigators wrote.

Dr. Kurian reported that Stanford University received research funding from Myriad Genetics for an unrelated project. No other conflicts of interest were reported.

SOURCE: Kurian AW et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0644.

 

The introduction of multiple-gene sequencing led to a substantial increase in detection of pathogenic variants in a study of women with breast cancer treated in community practice, results of one retrospective study show.

Multiple-gene sequencing rapidly replaced BRCA1/2 only testing over a 2-year period in the study, driven in part by technological advances and regulatory changes that made comprehensive low-cost genetic testing more accessible, investigators wrote. The report was published in JAMA Oncology.

That quick uptake increased detection of genetic variants that could change care, with no associated increase in prophylactic mastectomy over that same time period, said Allison W. Kurian, MD, of Stanford (Calif.) University, and her coinvestigators.

“The greater yield of clinically relevant information with multiple-gene sequencing offers a major potential advantage over more limited BRCA1/2-only tests,” noted Dr. Kurian and her colleagues.

Their analysis included 5,026 women with stage 0-II breast cancer diagnosed from January 2013 to December 2015 and enrolled in the Individualized Cancer Care (iCan Care) study. That study started enrolling 1 month before a U.S. Supreme Court decision on gene patents, which led to lower costs for multiple-gene sequencing tests for breast cancer risk, Dr. Kurian and her coinvestigators said.

Overall, about one-quarter of women in the study had genetic testing, and that did not change over time. What did change over time was the number of women undergoing multiple-gene testing: In 2013, only 25.6% underwent multiple-gene sequencing, versus 74.4% for BRCA1/2-only testing; by 2015, those figures flipped to 66.5% and 33.5%, respectively.

Multiple-gene sequencing increased detection of pathogenic variants in women at average pretest risk (4.2% versus 2.2% for BRCA1/2-only testing), according to the reported data. Detection was increased in women at high pretest risk due to young age, triple-negative breast cancer, or other factors (12% versus 7.8%).

 

Prophylactic mastectomy was most strongly associated with detection of pathogenic BRCA1/2 variants, according to Dr. Kurian and her coinvestigators. More women with those variants strongly considered the procedure and had it recommended by their surgeons, and ultimately, significantly more underwent the procedure (79.0% versus 37.6% for other pathogenic variants; P less than .001).

While those mastectomy outcomes were reassuring, Dr. Kurian and her colleagues said, their research uncovered two “important limitations” to multiple-gene sequencing that should be addressed.

They found that testing was done post surgically in 32.5% of women who had multiple-gene sequencing, compared with 19.9% of women who had BRCA1/2-only testing. Postsurgical testing is “too late” and limits its use to make decisions about surgical prevention of second cancers, they said.

They also found racial disparities in detection of variants of unknown significance (VUS). In particular, VUS were detected in 23.7% of white patients, compared with 44.5% of black patients and 50.9% of Asian patients. That’s because most of the genes were first sequenced in white patients, the investigators noted.

 

In previous experience with BRCA1/2 testing, extensive VUS reclassification occurred after broader testing within the population over 2 decades.

“It is a crucial priority to resolve persistent racial/ethnic disparities in genetic information, particularly as increasingly comprehensive sequencing tests enter clinical practice,” the investigators wrote.

Dr. Kurian reported that Stanford University received research funding from Myriad Genetics for an unrelated project. No other conflicts of interest were reported.

SOURCE: Kurian AW et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0644.

 

The introduction of multiple-gene sequencing led to a substantial increase in detection of pathogenic variants in a study of women with breast cancer treated in community practice, results of one retrospective study show.

Multiple-gene sequencing rapidly replaced BRCA1/2 only testing over a 2-year period in the study, driven in part by technological advances and regulatory changes that made comprehensive low-cost genetic testing more accessible, investigators wrote. The report was published in JAMA Oncology.

That quick uptake increased detection of genetic variants that could change care, with no associated increase in prophylactic mastectomy over that same time period, said Allison W. Kurian, MD, of Stanford (Calif.) University, and her coinvestigators.

“The greater yield of clinically relevant information with multiple-gene sequencing offers a major potential advantage over more limited BRCA1/2-only tests,” noted Dr. Kurian and her colleagues.

Their analysis included 5,026 women with stage 0-II breast cancer diagnosed from January 2013 to December 2015 and enrolled in the Individualized Cancer Care (iCan Care) study. That study started enrolling 1 month before a U.S. Supreme Court decision on gene patents, which led to lower costs for multiple-gene sequencing tests for breast cancer risk, Dr. Kurian and her coinvestigators said.

Overall, about one-quarter of women in the study had genetic testing, and that did not change over time. What did change over time was the number of women undergoing multiple-gene testing: In 2013, only 25.6% underwent multiple-gene sequencing, versus 74.4% for BRCA1/2-only testing; by 2015, those figures flipped to 66.5% and 33.5%, respectively.

Multiple-gene sequencing increased detection of pathogenic variants in women at average pretest risk (4.2% versus 2.2% for BRCA1/2-only testing), according to the reported data. Detection was increased in women at high pretest risk due to young age, triple-negative breast cancer, or other factors (12% versus 7.8%).

 

Prophylactic mastectomy was most strongly associated with detection of pathogenic BRCA1/2 variants, according to Dr. Kurian and her coinvestigators. More women with those variants strongly considered the procedure and had it recommended by their surgeons, and ultimately, significantly more underwent the procedure (79.0% versus 37.6% for other pathogenic variants; P less than .001).

While those mastectomy outcomes were reassuring, Dr. Kurian and her colleagues said, their research uncovered two “important limitations” to multiple-gene sequencing that should be addressed.

They found that testing was done post surgically in 32.5% of women who had multiple-gene sequencing, compared with 19.9% of women who had BRCA1/2-only testing. Postsurgical testing is “too late” and limits its use to make decisions about surgical prevention of second cancers, they said.

They also found racial disparities in detection of variants of unknown significance (VUS). In particular, VUS were detected in 23.7% of white patients, compared with 44.5% of black patients and 50.9% of Asian patients. That’s because most of the genes were first sequenced in white patients, the investigators noted.

 

In previous experience with BRCA1/2 testing, extensive VUS reclassification occurred after broader testing within the population over 2 decades.

“It is a crucial priority to resolve persistent racial/ethnic disparities in genetic information, particularly as increasingly comprehensive sequencing tests enter clinical practice,” the investigators wrote.

Dr. Kurian reported that Stanford University received research funding from Myriad Genetics for an unrelated project. No other conflicts of interest were reported.

SOURCE: Kurian AW et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0644.