Differences Between Genetic, Genomic Testing in Breast Cancer

The approval of Orserdu, an oral treatment, has led to new novel oral treatments that may perform better than the standard of care injection in certain breast cancer subtypes.

Patients with metastatic breast cancer whose disease is HER2-negative and have BRCA mutations showed better outcomes when receiving oral Lynparza (olaparib), compared with chemotherapy, according to Dr. Kevin Kalinsky.

Kalinsky is a professor and director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University. He recently discussed genetics and genomics for patients with breast cancer at the 2024 CURE® Educated Patient® Breast Cancer Summit at the annual Miami Breast Cancer Conference.

According to the American Cancer Society, genes are pieces of DNA, which are responsible for carrying instructions to make proteins. The study of genes is called genetics.

Meanwhile, genomics is the study of the entire set of a person’s genes, known as their genome, which entails how genes interact with each other, along with the person’s environment, the American Cancer Society also defines. Genomics helps researchers identify the gene and protein changes within cancer cells.

Genetic Testing for Patients with Breast Cancer Who Have BRCA Mutations

Regarding genetic testing for BRCA1/2 mutations, Kalinsky noted that guidelines from the National Comprehensive Cancer Network, included having “a strong family history, [whether] patients had triple-negative breast cancer and if patients have a male relative [with breast cancer] because there’s a higher rate of having BRCA 2 mutations for patients with a family history of male breast cancer,” he said.

However, the American Society of Clinical Oncology (ASCO) released recent recommendations, stating patients should be offered testing for BRCA 1/2if they recently received a diagnosis of stage 1 to 3 or de novo stage 4 breast cancer and are aged 65 or younger at diagnosis.

Kalinsky noted that this change is “way more inclusive than it had been,” for patients’ eligibility, now opening up the dialogue between patients and their doctors about testing.

For patients aged 65 or older, “it’s really at the discretion of the conversation that we’re having with our patients,” Kalinsky said.

Factors that may apply to patients aged 65 and older who can be offered BRCA mutation testing include patients who have triple-negative breast cancer, patients eligible to receive Lynparza, patients who are part of a higher-risk population such as people of Ashkenazi Jewish descent or having a family history that may suggest a higher risk of a pathogenic mutation, according to recommendations from ASCO.

“Now, the guidelines really have changed because for a long time, we were debating whether we should be doing genetic testing on everybody, but now we have opened this up by increasing the number of patients we should be testing,” Kalinsky explained.

Available Treatment for Breast Cancer and BRCA Mutations

“For patients with metastatic breast cancer that is HER2-negative, giving pills like [Lynparza] and [Talzenna (talazoparib)] it took longer for the cancer to grow,” explained Kalinsky. “This led to the approval of [Lynparza] and [Talzenna] — there are two approved drugs for patients with BRCA mutations.”

Following the two approvals, Kalinsky noted, a study called OlympiA evaluated the effect of Lynparza after surgery for patients with germline BRCA1 or BRCA2-mutated estrogen receptor (ER)-positive, HER2-negative and triple-negative breast cancer.

There were 1,836 patients within the study who were randomized into two cohorts to receive either Lynparza or a placebo pill twice daily for one year “to see if [the treatment] decreased the likelihood of recurrence, strictly in patients with inherited BRCA mutations,” Kalinsky said.

According to the data from the study, patients who received Lynparza “were less likely to have a recurrence than patients who received placebo,” explained Kalinsky. Data also demonstrated that the spread of breast cancer to another area of the body, meaning Lynparza helped prevent the cancer from coming back and spreading.

Patients from the OlympiA study had a median follow-up of 3.5 years, Kalinsky said, in which the researchers established that patients who received Lynparza lived longer than patients who received a placebo.

Genomic Testing for Patients With Breast Cancer

“[Genomic testing is] looking at the tumor or looking at the circulating tumor DNA, which is looking in the blood to see if there are any cancer cells that are being shed and evaluating those to look for mutations of the cancer,” Kalinsky clarified. “[These are] mutations in the cancer, not hereditary mutations.”

A type of mutation called ESR1 develops due to resistance to endocrine (hormone) therapy that patients with ER-positive breast cancer had previously received, Kalinsky explained.

Based on this mutation’s effect, ASCO released a recommendation update for a patient population with ER-positive, HER2-negative metastatic breast cancer.

The recommendation from ASCO emphasized routine testing for patients who experienced an emergence of ESR1 mutations when their breast cancer progressed (worsened or spread) or came back after receiving endocrine therapy, with or without a CDK4/6 inhibitor.

Specifically, genomic testing should “start with blood because it has greater sensitivity,” said Kalinsky. He noted that if the testing via blood does not give doctors the information they are looking for, then testing on the tumor is next or via another biopsy to identify whether the ESR1 mutation is present.

Treatments for Patients With ESR1 Mutations

A randomized phase 3 trial called EMERALD evaluated the difference in effectiveness in oral Orserdu (elacestrant), compared with standard of care, which led to the approval of Orserdu in early 2023 for patients with ER-positive, HER2-negative, ESR1 mutations.

Other oral treatments for this patient population have emerged after the EMERALD trial, Kalinsky said, some of which are being evaluated in trials.

“There are other drugs that are similar to [Orserdu] that are pills because, for a long time, all we had was [Faslodex (fulvestrant)], which is an injection given in the buttock,” Kalinsky added. “But there are other oral drugs that are targeting the estrogen receptor beyond those that I’m even listing.”

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