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Targeted Treatment for Early-Stage Breast Cancers

Targeted Treatment for Early-Stage Breast Cancers
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Published on August 24, 2021

BRCA+ Patients Could Benefit From Additional Targeted Treatment

People with high-risk HER2-negative breast cancer and inherited or germline BRCA1 or BRCA2 mutations have a significant risk of cancer recurrence, even after receiving standard therapies such as chemotherapy and endocrine (hormone) therapy before or after surgery. A recent phase 3 clinical trial showed that patients with this form of breast cancer may benefit from an additional targeted treatment following initial treatment.

The randomized OlympiA study investigated olaparib (Lynparza), which was given to patients after they completed surgery and chemotherapy. Olaparib interferes with the PARP enzyme, which is involved in repairing damaged DNA. Cancer cells with BRCA1 or BRCA2 mutations already have problems with DNA repair and knocking out this additional DNA repair enzyme can prove lethal for these cells. Olaparib has been approved by the U.S. Food and Drug Administration for treatment of certain individuals with metastatic breast cancer but has not been approved for those with early-stage disease.

Researchers from many institutions recruited 1,836 trial participants between June 2014 and May 2019. Patients were randomly assigned to one year of oral olaparib or a placebo. The median age of participants was 42 for those taking olaparib and 43 for those assigned to get the placebo. “The participants were unusually young for a breast cancer trial, and the rate of mastectomy was high, consistent with genetic predisposition; BRCA1 mutation was more common than BRCA2, but all characteristics were evenly balanced between arms,” said Andrew Tutt, PhD, MBChB, a breast oncologist at the Institute of Cancer Research and King’s College London. Dr. Tutt shared the results at the American Society of Clinical Oncology (ASCO) Annual Meeting held in June 2021.

The primary endpoint was invasive disease-free survival (IDFS), or the proportion of people who were still alive and had not developed recurrence of an invasive breast cancer or a second primary cancer after a set amount of time. After three years median follow-up, IDFS was around 86% for those who took olaparib, versus 77% for those who took the placebo. Distant disease-free survival, or the proportion of people who were alive and had not developed distant metastases, was around 88% in the olaparib group, compared with 80% in the placebo group.

“Olaparib for one year after completing chemotherapy has the potential to improve invasive and distant disease-free survival in patients with germline BRCA1/2 mutations and high-risk early breast cancer” Dr. Tutt concluded.

Side Effects

Nausea, fatigue, vomiting, and anemia were the most common adverse events associated with taking olaparib. Overall, toxicity was limited and manageable and did not affect global patient-reported quality of life, Dr. Tutt said. Patient-reported outcomes are especially important because what may seem tolerable from a physician’s perspective may impact a person’s ability to dress, move around comfortably, eat, work, and exercise.

The trial provides evidence that germline BRCA1 and BRCA2 sequencing can guide the selection of systemic therapy in early breast cancer, the research team concluded. Currently, recommendations vary on which breast cancer patients should get genetic testing. A recent study of women with breast cancer in California and Georgia found that about one-quarter got genetic testing.

~Lauren Evoy Davis

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