What Is a CHEK2 Gene Mutation? What You Need to Know

What Is an Inherited CHEK2 Mutation? What You Need to Know – Summary

• The name CHEK2 comes from "Checkpoint Kinase 2". The CHEK2 gene is located on chromosome 22 and helps control how cells divide.
• People who carry an inherited CHEK2 mutation have a higher risk of certain cancers. This mutation has screening and prevention guidelines for certain cancers for people who carry it. Clinical trials are also available for people who test positive for a CHEK2 mutation.
• People diagnosed with a CHEK2 mutation who have also been diagnosed with cancer may participate in clinical trials or receive certain treatments.
• Both men and women can carry a mutation in the CHEK2 gene.

Which Cancers Have an Increased Risk With an Inherited CHEK2 Mutation?

If you test positive for an inherited CHEK2 mutation, it is recommended that you talk to a genetics specialist who can review your personal and family cancer history and help you choose the best plan to manage your cancer risk.

Breast Cancer Risk

• Women have an approximately 37% lifetime risk.
• Men may also have a higher risk of breast cancer, but the exact risk is unknown.

How Should Risk Be Managed for People Who Carry an Inherited CHEK2 Mutation?

The United States National Comprehensive Cancer Network (NCCN) provides risk management guidelines for men and women with a CHEK2 mutation. You are advised to consult a genetics specialist who can review your personal and family cancer history and help determine the best risk management plan.

Breast Cancer Screening and Prevention

• Starting in the early 40s or, if a family member has been diagnosed, 5- 10 years earlier than their age at diagnosis (no later than age 40), an annual mammogram screening (3D mammograms if appropriate) should be performed.
• Starting in the early 40s or, if a family member has been diagnosed, 5- 10 years earlier than their age at diagnosis, contrast-enhanced breast MRI (MRG) is a scan to consider.
• For women who carry a CHEK2 mutation, there is insufficient evidence of a benefit from risk-reducing mastectomy (surgical removal of the breasts for prevention). Experts recommend considering mastectomy based on a family history of breast cancer.

Colon Cancer Screening and Prevention

• Starting in the early 40s (or 5 – 10 years earlier than the age at diagnosis of a close relative with colon cancer), every 5 years a colonoscopy should be performed.

Cancer Treatment for People Who Carry a CHEK2 Mutation

People with an inherited CHEK2 mutation who have been diagnosed with cancer may have different treatment options from people who do not carry a mutation.

If you have an inherited CHEK2 mutation, have been diagnosed with cancer, and any of the following apply to you, you may wish to talk to your doctor about your medical options.

• You are making a decision about breast cancer surgery.
• You have metastatic prostate cancer.
• You have advanced ovarian (female ovary) cancer.

Surgical Decisions for Women Diagnosed With Breast Cancer

Because of the high risk of a second breast cancer, women who test positive for an inherited mutation in the CHEK2 gene and are diagnosed with breast cancer may choose bilateral mastectomy rather than lumpectomy and radiotherapy. Mutation carriers who undergo mastectomy still have a chance of developing a second breast cancer.

PARP Inhibitors

PARP inhibitors are a type of targeted therapy that works by blocking a protein used to repair damaged DNA. They were initially developed for people with an inherited BRCA1 or BRCA2 mutation to treat cancer. Since then, research and additional FDA approvals have expanded the use of PARP inhibitors to more situations. People with a CHEK2 mutation who have been diagnosed with cancer may wish to consult their doctors about PARP inhibitor treatment.

Metastatic Prostate Cancer

The PARP inhibitor Lynparza (olaparib), for men with a mutation in CHEK2 or another gene involved in a certain type of DNA damage repair who have metastatic castration-resistant prostate cancer, has received FDA approval to treat this condition. Lynparza is approved for use after enzalutamide (Xtandi) or abiraterone (Zytiga) in men whose prostate cancer has progressed.

PARP Inhibitors for Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Various PARP inhibitors have been approved to treat ovarian cancer at different stages of the disease. In some cases, a tumor biomarker test known as HRD (homologous recombination deficiency) testing can help women who carry a CHEK2 mutation and have advanced ovarian cancer find out whether they may benefit from a PARP inhibitor.

• Advanced Cancer That Recurs After Third-Line Treatment:
  • For women with advanced ovarian cancer that recurs after third-line treatment and an inherited CHEK2 mutation, HRD testing can guide the use of the PARP inhibitor Zejula (niraparib) by helping them find out whether they may benefit from it.

• Maintenance Therapy After First-Line Treatment:

• • HRD testing helps women with advanced ovarian cancer and an inherited CHEK2 mutation determine whether, after first-line platinum chemotherapy, maintenance therapy with bevasizumab combined with the PARP inhibitor Lynparza may be beneficial.
  • Zejula has received FDA approval for maintenance therapy in women with advanced ovarian, fallopian tube, or primary peritoneal cancer who have had a complete or partial response to first-line platinum-based chemotherapy. HRD testing is not required for maintenance therapy with Zejula.

• Maintenance Therapy After Treatment for Recurrent Cancer:
  • Zejula, Rubraca (rucaparib) and Lynparza are all approved for maintenance therapy in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a complete or partial response to platinum-based chemotherapy. None of these drugs requires HRD testing in this situation.

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