1. DiGiulio, Sarah

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In women at high risk of having hereditary breast cancer, genetic testing can have significant implications for better management of that cancer. Previously, it was considered unlikely that older women with breast cancer had disease that was hereditary and would benefit from genetic testing.

Nadine Tung, MD. Nad... - Click to enlarge in new windowNadine Tung, MD. Nadine Tung, MD

Now new data from 26,707 women from population-based studies who underwent pathogenic variant testing in germline predisposition genes (51.5% had breast cancer and 48.5% did not) suggests more older women may have markers of hereditary disease than was previously thought. The results revealed that, of the sample, frequency of pathogenic variants in predisposition genes was 3.18 percent for women with breast cancer and 1.48 percent for unaffected women over age 65 years. The study was published online ahead of print earlier this year (J Clin Oncol 2021; doi: 10.1200/JCO.21.00531).


"This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening," the study authors noted in the conclusion of the paper.


In an editorial that accompanies the research, Nadine Tung, MD, Professor of Medicine at Harvard Medical School and Director of Cancer Risk and Prevention Program and Breast Medical Oncology at Beth Israel Deaconess Medical Center, said the findings are practice-changing (J Clin Oncol 2021; doi: 10.1200/JCO.21.01761). Here's what she told Oncology Times about the new research in an interview.


1 Why were the findings from the study that accompanies your editorial (on risk of late-onset breast cancer in genetically predisposed women) significant?

"The findings from Boddicker, et al, were significant because they help clarify which patients with breast cancer diagnosed after age 65 warrant genetic testing. Using a threshold frequency for a pathogenic or likely pathogenic variant (or mutation) of 2.5 percent to warrant testing, their results justify genetic testing in patients with triple-negative breast cancer diagnosed after age 65. (The threshold of 2.5% is the frequency of a BRCA1 or BRCA2 mutation in the Ashkenazi Jewish population for whom universal BRCA testing has been advocated).


"Before this study, testing had only been recommended for patients with triple-negative breast cancer diagnosed by age 60. Thus, these results were practice-changing; the National Comprehensive Cancer Network now recommends testing for all patients with triple-negative breast cancer, at any age."


2 Should all patients with breast cancer (regardless of age or cancer type) undergo genetic testing?

"Some, including the American Society of Breast Surgeons, have advocated genetic testing for all patients with breast cancer.


"But, if we use previous data from Yadav, et al, (J Clin Oncol 2020; doi: 10.1200/JCO.19.02190)-which justifies universal genetic testing for all women diagnosed with breast cancer by age 60 or 65-and combine those results with the current results [from the trial from Boddicker's group], an alternative to universal testing is the approach to test all women with breast cancer diagnosed by age 60 or 65, and use family history and personal cancer history to justify testing in older women.


"Those with triple-negative breast cancer would be tested at any age of diagnosis because [the new data from the trial from] Boddicker, et al, found that 3 percent of women diagnosed with triple-negative breast cancer after age 65 had a germline (inherited) mutation in BRCA1, BRCA2, or PALB2, and 3.3 percent of women diagnosed with triple-negative breast cancer after age 60 had a mutation in high-risk breast cancer genes.


"But for women diagnosed after age 65 with ER+ or HER2-positive disease, personal or family history of another relevant cancer would be needed for testing. Those with a first degree relative with breast cancer may merit testing, since Boddicker, et al, found that these women have a 2.3 percent chance of having a mutation in BRCA1/2 or PALB2. But those with an ER+ breast cancer and no first degree relative with breast cancer had less than a 1 percent chance of having a mutation.


"Compared with testing all women with breast cancer, this alternative approach spares a significant percentage of women who do not need genetic testing. Unnecessary genetic testing can lead to harms from misinterpretation and overtreatment of some genetic findings. In addition, given the limited number of genetic experts, trying to limit genetic testing to those who truly need it has merit."


3 Considering that this approach would increase the number of women who should undergo genetic testing, are there implications for genetic counselors?

"As the threshold for genetic testing decreases (or the number of patients with breast and other cancers requiring genetic testing increases), the shortage of genetic counselors will be even more evident. Thus, we need to begin to adopt alternative models of germline genetic testing such as oncologist-initiated testing, ensuring that patients still receive enough information to provide informed consent.


"That way, genetic counselors are utilized more for individuals found to have a pathogenic or likely pathogenic variant (a mutation) or other genetic findings that require genetic expertise for interpretation. The majority of patients who undergo genetic testing will not have a mutation, and may not need a genetic counselor if sufficient information can be provided to patients before genetic testing is done."