NEW YORK (GenomeWeb) – Women with cancer who are found to have pathogenic genetic variants may receive care that does not reflect what current evidence-based practice guidelines indicate they should receive, according to an analysis performed by Stanford University's Allison Kurian and her colleagues.
While BRCA1 and BRCA2 testing have been available to patients for years, testing of other genes has only recently become prevalent, and Kurian and her colleagues sought to examine whether there have been shifts in the care patients receive after they undergo genetic testing.
Using data from the Surveillance, Epidemiology, and End Results Program, they examined patients' genetic testing results — if they had a pathogenic variant, variant of uncertain significance, or a negative result — and what treatment they subsequently received.
"Our hypotheses were that we might see some evidence of potentially people doing things which were not consistent with practice guidelines in relation to finding certain genetic test results," Kurian said in an interview. She presented her team's findings this weekend at the American Society of Clinical Oncology annual meeting.
Kurian and her team linked SEER data from California and Georgia, covering a total of 15 million people, to genetic testing data from four labs: Ambry Genetics, GeneDx, Invitae, and Myriad Genetics.
For their new analysis, they pulled genetic testing results data on women over the age of 20 years who were diagnosed with unilateral breast cancer between 2014 and 2015, forming a cohort of 82,017 individuals. About nine percent of these women had pathogenic variants in either BRCA1, BRCA2, or in other genes, including ATM, BARD1, CHEK2, PALB2, NBN, and TP53.
The researchers then examined which of three treatments the patients may have received: bilateral mastectomy, radiation therapy, and chemotherapy.
After adjusting for factors like age, race, and socioeconomic status, Kurian and her colleagues found that women who had pathogenic variants in cancer risk genes were more likely to receive a bilateral mastectomy even as they had unilateral disease. In particular, they found that bilateral mastectomy was 4.4 times morecommon among patients with pathogenic variants in BRCA1 and BRCA2.
Women with pathogenic variants in BRCA1 and BRCA2 are at a high risk of developing contralateral breast cancer, an 83 percent risk for BRCA1 carriers and 62 percent for BRCA2 carriers of developing contralateral breast cancer by age 70.
But Kurian and her colleagues also found bilateral mastectomy to be common among patients with pathogenic variants in other genes — about 1.67 times as common — where there is less evidence that patients may benefit from risk-reducing mastectomy.
"I think there is question about whether it was appropriate to do those surgeries in people who had pathogenic variants in other genes, when guidelines actually generally do not recommend it," she added, referring primarily to guidelines from the National Comprehensive Cancer Network, which she noted overlap with other guidelines from ASCO and the American Cancer Society.
Additionally, she and her colleagues found that women who had pathogenic variants in cancer risk genes were more likely to receive adjuvant chemotherapy when it wasn't indicated. At the same time, these women were less likely to receive radiation treatment following a lumpectomy when it was indicated.
In particular, they found that women who had pathogenic variants were a third more likely to received adjuvant chemotherapy, and about 30 percent less likely to receive radiation treatment following a lumpectomy.
These findings suggested to Kurian that there is both over- and under treatment of breast cancer patients found to have pathogenic variants. While she cautioned that she and her colleagues did not survey physicians or patients in this study to ask why they pursued the treatment approaches they did, she said that there have been fears that radiation therapy might be more toxic or induce secondary cancers, which could dissuade patients and physicians from taking that route.
She added, though, there is evidence that is not the case. At the same time, she said there has been speculation that patients with pathogenic variants may do better with chemotherapy, though she added there isn't strong evidence there either. Still, she noted that these beliefs might account for these deviations from guidelines.
"This is not a randomized trial — we don't know exactly cause and effects — but there is some significant evidence in this very large population-based study that treatment may be being given inappropriately on the basis of pathogenic variants," Kurian said.
This concern, she added, merits further study and could mean better awareness and perhaps education of clinicians regarding guidelines is warranted. One avenue that Kurian and her colleagues aim to next pursue is to ask clinicians why they chose one treatment approach over another. "I think it will be valuable, because, as it is, we're only been able to report associations, and we can't comment further on what actually was happening in the exam room," she said.
In addition to pathogenic variants, Kurian and her colleagues also examined what treatments patients with variants of uncertain significance received.
In a study that appeared in the Journal of Clinical Oncology in 2017, she and her colleagues reported that a number of breast cancer surgeons tended to treat variants of uncertain significance in the BRCA1 or BRCA2 genes like pathogenic variants, when guidelines instead suggest they should be treated like negative results. That meant that patients with VUS frequently underwent bilateral mastectomy.
But in this analysis, they found that patients with variants of uncertain significance were not getting bilateral mastectomies at the same rate as patients with pathogenic BRCA1 or BRCA2 mutations. They reported that 57.5 percent of patients with pathogenic BRCA1 or BRCA2 mutations underwent bilateral mastectomy, while 24.4 percent of patients with variants of uncertain significance did.
"We did not see, in this setting, a signal for more bilateral mastectomy with variants of uncertain significance, which I thought was reassuring," Kurian said.