Study: Racial and ethnic differences in genetic testing among young breast cancer survivors

IN-DEPTH REVIEW OF RESEARCH

Study background:

About 19 percent of women who are diagnosed with breast cancer are younger than age 50. Most of these women are recommended to undergo genetic testing. This reflects the fact that young women with breast cancer are more likely than the general population to have a mutation in a gene such as BRCA1, BRCA2, CDH1, PTEN, STK11, TP53,  PALB2 or othersthat are associated with cancer. Young women are more likely than postmenopausal women to have aggressive cancers, have triple-negative cancer and have worse outcomes.  Multigene panel testing—a single test that searches for mutations in many genes—is a way to be thorough in determining whether a person carries a mutation in one of these genes.

Breast cancer patients who have a known inherited mutation have different options for treatment (such as taking PARP inhibitors to treat HER2-negative tumors) and prevention (such as prophylactic surgery to remove their opposite, healthy breast or their ovaries, or intensified breast screening).

Several smaller studies found that young breast cancer patients have genetic testing for inherited mutations less often than older women. This study seeks to understand the frequency and factors that affect the choice to have genetic testing and the types of mutations that are found among young women with breast cancer.

Researchers of this study wanted to know:

The frequency and factors that affect whether a young woman with breast cancer has genetic testing and what types of mutations are found.

Populations looked at in this study:

This study looked at health record data from 1,503 young women who were diagnosed with breast cancer before age 50 between 2007 and 2017 at Columbia University. Women with either invasive breast cancer or ductal carcinoma in situ (DCIS) were eligible.

On average, participating patients were 43 years old:

• 42% were non-Hispanic white
• 13% were non-Hispanic black
• 25% were Hispanic
• 10% were Asian
• 9% were of unknown race or ethnicity

Among participants, 60 percent had private insurance, 23 percent had Medicaid, 7 percent had Medicare (due to disability or other health issues) and 9 percent had other insurance or were uninsured.

Study design:

This was a retrospective study of women who were diagnosed with breast cancer. Researchers identified patients from the New York-Presbyterian Hospital Tumor Registry at Columbia University Irving Medical Center. If patients were diagnosed with invasive breast cancer or ductal carcinoma in situ (DCIS) and had available records, researchers determined if that patient had genetic testing and what the results were.

Study findings:  

Completion of genetic testing did not differ by race but it was affected by other factors.

• 683 patients (45%) completed genetic testing.
• Patients of different race, ethnicity or insurance status completed genetic testing at similar rates.
• Patients who completed genetic testing were more likely to:
  • be younger  
  • be married
  • have a family history of breast cancer
  • have stage I breast cancer
  • be diagnosed after 2013
• The rate of genetic testing has increased over time:
  • A substantial increase in genetic testing occurred in 2013. This coincides with the clarification of coverage under the Affordable Care Act, Angelina Jolie announcing her BRCA status and conclusion of the Supreme Court in the case of Molecular Pathology versus Myriad Genetics.  This decision, which overturned Myriad’s patent on the BRCA1 and BRCA2  genes allowed testing from more commercial labs and low cost testing options.
  • 73% of patients in this study diagnosed with breast cancer in 2015 completed genetic testing.

Genetic test results

• There are two kinds of mutations that were looked at in study:
  • mutations with a known association with cancer called pathogenic/likely pathogenic (P/LP)  mutations.
  • mutations with an unclear effect on cancer called Variants of Uncertain Significance (VUS).
• 217 of patients (32 percent) who completed genetic testing had a mutation of some kind (either P/LP or VUS) in one of several genes and 466 (68%) had no P/LP mutation or VUS.
  • Among patients who had a mutation:
    • 87 (13 percent) had pathogenic or likely pathogenic (P/LP) mutations in the following genes:
      • BRCA1 (46% of P/LP mutations)
      • BRCA2 (28% of P/LP mutations)
      • CHEK2 (7% of P/LP mutations)
      • ATM (5% of P/LP mutations)
      • 9 other genes (15% of P/LP mutations)
    • 130 (14%) had a VUS in the following genes:
      • 11% in BRCA1
      • 11% in BRCA2 
      • 10% in ATM 
      • 7% in CHEK2 
      • 32 other genes  (61% of VUS)

The rate and types of mutations differed by racial or ethnic group.

• In Black women, 32% had an inherited mutation
  • 18% had a P/LP mutation
  • 14% had a VUS
• In Asian women, 30% had an inherited mutation
  • 8% had a P/LP mutation
  • 22% had a VUS)
• In Hispanic women, 27% has an inherited mutation:
  • 8% had a P/LP mutation
  • 19% had a VUS
• In white women, 25% had an inherited mutation:
  • 16% had a P/LP mutation
  • 9% had a VUS)
• Black patients were the most likely to have a gene change (either a VUS or a pathogenic/likely pathogenic mutation) followed by Asian and Hispanic. White patients were least likely to have any gene change.
• Black and white patients were more likely than Asian or Hispanic patients to have a mutation classified as pathogenic/likely pathogenic
• Asian and Hispanic patients were more likely than black or white patients to have a VUS.
• The authors note that these high VUS rates among Asian and Hispanic patients match other studies. They suggest that this is due to less understanding of the normal range of mutations in these populations. It is possible that more research on a portion of these VUS would allow their reclassification as harmless or harmful mutations.

Limitations:

This study has several limitations:

• Because this is a retrospective study that evaluates medical records, information on genetic testing may be incomplete or inaccurate. Underreporting of genetic testing to healthcare providers may have occurred and may be more prevalent for one group than others (e.g., among underinsured patients versus insured patients).
• Although the demographics of the study included a diverse sample of patients in terms of ethnic/racial groups, this study took place at one location in New York City.  The results may be different in other geographic locations, clinical centers or populations. It is unclear how generalizable the conclusions may be.
• Researchers stated that they tracked participants who had BRCA1/2 testing compared to multi-panel testing, but they did not indicate specific numbers or to what degree this was done. This might change the frequency of people who have mutations in genes other than BRCA1/2—gene mutations that are not looked for will not be found.

Conclusions:

Among young breast cancer patients, 18 percent of black women, 16 percent of white women, 8 percent of Hispanic and 8 percent of Asian women had an inherited mutation in a breast cancer gene.  The presence of an inherited mutation associated with increased cancer risk may change treatment and preventive options. Consulting with a genetic counselor after genetic testing is important to understand the implications of genetic testing results.

As these researchers state:

 "Due to uncertainty about the clinical implications ..., our findings underscore the need for targeted genetic counseling education, particularly among young minority women."

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Posted 02/28/20