Topic: Inherited BRCA mutations may affect CDK4/6 treatment outcomes
Several studies suggest that people with an inherited BRCA1 or BRCA2 mutation and hormone receptor-positive, HER2-negative breast cancer may have a shorter response to CDK4/6 inhibitors than people without these mutations. (posted 10/21/2026)
By: Piri Welcsh, PhD
Reviewed by: Allison Kurian, MD, MSc
RELEVANCE
Most relevant for: People with HR-positive, HER2-negative breast cancer who have an inherited BRCA1 or BRCA2 mutation who are considering treatment with a CDK4/6 inhibitor.
It may also be relevant for:
- people with breast cancer
- people with ER/PR + cancer
- people newly diagnosed with cancer
- people with a genetic mutation linked to cancer risk
- people with metastatic or advanced cancer
Relevance: Medium
Strength of Science: Medium
Research Timeline: Human Research
What is this topic about?
Several studies (see References below) suggest that people with a or mutation may have less time before their cancer grows or worsens when treated with CDK4/6 inhibitors plus hormone therapy for hormone receptor-positive, breast cancer. Although each study had a small number of people with mutations, they found similar results: people with inherited mutations treated with CDK4/6 inhibitors had cancer that tended to grow or worsen sooner than people without these mutations.
What are CDK4/6 inhibitors?
CDK4/6 inhibitors are a type of that blocks proteins that help control how fast cells grow. They are used to treat advanced or breast cancer. They are also used for HR-positive breast cancer that has a high risk of recurrence. The drugs are usually given with hormone therapy to slow the growth of , breast cancer.
In the US, three CDK4/6 inhibitors are currently approved by the for frontline treatment of locally advanced or HR-positive/HER2-negative breast cancer: Verzenio (abemaciclib), Ibrance (palbociclib), and Kisqali (ribociclib). Verzenio and Kisqali have also been approved for the treatment of HR-positive/HER2-negative breast cancer that is at high risk for recurrence.
Tab 2: Bottom Line
What does this mean for me?
If you have a mutation and are being treated with CDK 4/6 inhibitors, you should not stop or change treatment based on these studies alone. Because the studies included few people with mutations and were mostly , they do not prove that mutations cause treatment resistance or show which treatment is best.
If you have breast cancer, an inherited mutation and a CDK4/6 inhibitor in your treatment plan, ask your doctor about the expected benefits and risks of the plan, how your response will be monitored and whether other treatment options may be appropriate for you.
If you have breast cancer and you have never had genetic testing for an , speak with your doctor about the benefits of genetic testing to help guide treatment decisions.
References
Safonov A, Marra A, Bandlamudi C, et al. Tumor suppressor heterozygosity and mediate resistance to front-line therapy in breast cancer. bioRxiv. Preprint posted online August 26, 2024.
Collins JM, Nordstrom BL, McLaurin KK, et al. A real-world evidence study of CDK4/6 inhibitor treatment patterns and outcomes in breast cancer by BRCA mutation status. Oncol Ther. 2021;9(2):575-589.
Bruno L, Ostinelli A, Waisberg F, et al. Cyclin-dependent kinase 4/6 inhibitor outcomes in patients with advanced breast cancer carrying pathogenic variants in repair-related genes. JCO Precis Oncol. 2022;6:e2100140.
André F, Su F, Solovieff N, et al. Pooled analysis of MONALEESA phase III advanced breast cancer trials. Ann Oncol. 2023;34(11):1003-1014.
Antrás JF, Ghamrasni SE, Zou J, et al. Impact of pathogenic BRCA1/2 and mutations and tumor aneuploidy in patients with HR+/HER2- breast cancer treated with CDK4/6 inhibitors. J Clin Oncol. 2023;41:16s (suppl; abstr 1075).
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to ensure scientific integrity.
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posted 10/21/2026
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