<i>BRCA</i> Testing in EBC and Adjuvant PARP Inhibition
Current Essential Testing in Early Breast Cancer: A Focus on BRCA Testing and Adjuvant PARP Inhibition

Released: November 17, 2022

Expiration: November 16, 2023

Charles E. Geyer, Jr.
Charles E. Geyer, Jr., MD

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Key Takeaways

  • Adjuvant therapy with olaparib is associated with a survival benefit in patients with pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk HER2-negative early breast cancer.
  • It is essential that appropriate patients with high-risk early breast cancer be tested for gBRCA1/2pv per guideline recommendations and assessed for eligibility for adjuvant olaparib.

Olaparib is now approved by the FDA in the adjuvant setting for adult patients with deleterious or suspected pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) with high-risk HER2-negative early breast cancer who have received neoadjuvant or adjuvant chemotherapy and completed surgery and radiation therapy. Use this new infographic to quickly obtain and share key insights on how to identify patients who may benefit from this treatment.

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The most common germline pathogenic variants in patients with breast cancer occur in BRCA1 and BRCA2 and are associated with aggressive clinical and biological features. Poly (ADP-ribose) polymerase (PARP) inhibitors have an established role in the metastatic setting for patients with gBRCA1/2pv. More recently, the OlympiA trial—which evaluated adjuvant olaparib vs placebo in patients with high-risk HER2-negative early breast cancer following completion of standard chemotherapy administered in the neoadjuvant or adjuvant settings, surgery, and radiation therapy—reported clinically meaningful improvements in primary and key secondary endpoints. At the planned first interim analysis with a median follow-up of 2.5 years reported in 2021, significant improvement in invasive disease–free survival and distant disease–free survival was demonstrated with 1 year of adjuvant olaparib compared with placebo. In the planned second interim analysis of overall survival with a median follow-up of 3.5 years, adjuvant olaparib was associated with significant improvement in overall survival. Subsequently, the FDA approved olaparib for the adjuvant treatment of adult patients with gBRCA1/2pv and high-risk HER2-negative early breast cancer who have received neoadjuvant or adjuvant chemotherapy.

Current guidelines recommend testing for gBRCA1/2pv in patients with a personal or family history of breast cancer meeting specific criteria, in patients with triple-negative breast cancer at any age, and to aid in treatment decisions for using PARP inhibitors in the metastatic setting or olaparib for high-risk HER2-negative early breast cancer. In addition, both the American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines recommend adjuvant olaparib for patients with triple-negative breast cancer or hormone receptor (HR)-positive/HER2-negative early breast cancer with gBRCA1/2pv meeting high-risk criteria, as per the OlympiA trial.

It is critical that appropriate patients are tested for germline BRCA status in the setting of high-risk early breast cancer and undergo assessment for adjuvant olaparib, if eligible. The OlympiA trial has validated that synthetic lethality is a unique mechanism of action that benefits patients with gBRCA1/2pv, and adjuvant olaparib offers the advantage of a targeted therapy with a survival benefit for this subset of patients.

Download a copy of the infographic here.

Your Thoughts?
What challenges do you experience in your practice when it comes to testing for BRCA and applying the results to the care of your patients who are newly diagnosed with early breast cancer? Answer the polling question and join the conversation in the discussion box below. 

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Which of the following most accurately describes which patients with early breast cancer your practice routinely tests for germline BRCA mutations?
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