Key takeaways

  • Homologous recombination repair (HRR) genes give cells instructions for repairing DNA damage. Mutations in your HRR genes limit DNA repair, raising prostate cancer recurrence and metastasis risk. In metastatic castration-resistant prostate cancer (mCRPC), HRR mutations appear in up to one-third of cases.
  • HRR mutations can be germline (inherited) or somatic (acquired over time). Doctors may use tumor and germline testing to help understand your condition, especially for metastatic disease or high-risk family history.
  • Knowing your HRR status can guide treatment choices for metastatic prostate cancer. Poly(ADP)-ribose polymerase (PARP) inhibitor medications like olaparib or rucaparib may help slow certain HRR-mutated cancers.

HRR gene mutations (changes) are linked to an increased risk of recurrence and metastasis in prostate cancer. This means that if the cancer cells have this type of mutation, prostate cancer is more likely to come back after treatment and spread to other parts of your body.

According to a 2024 research review, metastatic castration-resistant prostate cancer (mCRPC) has HRR gene changes in up to one-third of people who have the disease. Doctors refer to prostate cancer as mCPRC when it has spread to other parts of your body and no longer responds to treatment with hormone blockade therapy.

A 2025 study involving 566 people with prostate cancer found that HRR gene changes were also common in metastatic hormone-sensitive prostate cancer (mHSPC), occurring in 28.6% of cases. mHSPC is prostate cancer that has spread to other parts of your body and responds to hormone blockade therapy.

Read on to learn more about HRR gene-mutated prostate cancer.

HRR gene mutations are changes in certain genes that affect cells’ ability to repair double-strand damage in DNA. Repairing DNA damage is important for stopping the development and spread of cancer.

It’s possible to have gene mutations in one or more of the following HRR genes:

  • ATM
  • ATR
  • BARD1
  • BRCA1
  • BRCA2
  • BRIP1
  • CDK12
  • CHEK1
  • CHEK2
  • FANCA
  • FANCL
  • MLH1
  • MRE11A
  • NBN
  • PALB2
  • RAD51B
  • RAD51C
  • RAD51D
  • RAD54L

Mutations in these genes are linked to prostate cancer, as well as certain types of the following cancers:

  • ovarian cancer
  • breast cancer
  • pancreatic cancer

These mutations may contribute to the development of cancer or cause it to spread more quickly.

HRR gene mutations may be germline or somatic.

Germline mutations are hereditary, which means they pass from parents to children through an egg or sperm cell. This type of mutation is present from birth in every cell of a person’s body.

Somatic mutations are also known as acquired or sporadic mutations. They’re not hereditary, which means they don’t pass from parents to children. They happen during a person’s lifetime, starting in one cell and spreading when that cell divides.

Exposure to radiation or certain chemicals may cause DNA damage that leads to a somatic mutation. Random errors during cell division might also cause this type of mutation.

In people with prostate cancer who have certain risk factors, doctors may order genetic testing to check for tumor mutations, germline mutations, or both.

Tumor testing

Your doctor may recommend tumor testing if you have:

  • regional prostate cancer that has spread from your prostate to nearby tissues
  • metastatic prostate cancer that has spread to other parts of your body

They will perform a biopsy or collect a sample of tumor tissue during surgery to send to a laboratory for genetic testing. An expert in the lab will check the tissue for gene changes.

Your doctor might recommend germline testing if the tumor tests positive for gene changes. This testing will help them find out whether the gene changes are somatic mutations that occurred only in cancer cells or germline mutations that affect all the cells in your body.

Germline testing

Your doctor may recommend germline testing if you have prostate cancer and if any of the following risk factors apply to you:

  • The cancer has spread to other parts of your body.
  • The cancer has certain features that increase the risk of spread.
  • You have a family history of high risk germline mutations, such as BRCA1/BRCA2 mutations.
  • You have a strong family history of certain cancers that are linked to HRR germline mutations.
  • You have Ashkenazi Jewish ancestry.

They might also recommend germline testing if you have a tumor that has tested positive for gene changes.

Sometimes a doctor recommends germline testing even if a person has none of these risk factors.

You can talk with your doctor to learn more about the benefits and risks of germline testing. They may refer you to a genetic counselor who can help you learn more about germline testing, including what it involves.

For genetic testing, a healthcare professional will draw a sample of blood or take a saliva swab. They will send the sample to a lab, where experts will check for gene mutations. Your doctor or genetic counselor can help you understand the test results.

Learning whether you have prostate cancer with HRR gene mutations can help your doctor find the best treatment options. Certain treatments might be more effective for HRR gene-mutated cancer than others.

Finding out whether you have germline mutations can also help you understand your family cancer risk. Germline mutations can be passed from parents to children, and multiple family members might have the same mutation.

If you test positive for a germline mutation, your doctor or genetic counselor might recommend genetic testing or counseling for other family members. They might also recommend changes to family members’ cancer screening practices or other strategies to manage cancer risk.

Your doctor might recommend one or more of the following treatments for HRR gene-mutated prostate cancer:

  • surgery
  • radiation therapy
  • hormone therapy
  • targeted therapy
  • immunotherapy
  • chemotherapy

Hormone therapy involves using surgery or medication to lower testosterone levels. This is a common treatment for prostate cancer, but it may become less effective over time.

Poly(ADP)-ribose polymerase (PARP) inhibitors are targeted therapy drugs that make it harder for cells with HRR gene mutations to repair damaged DNA. Your doctor might prescribe this type of treatment to help shrink or slow the growth of metastatic prostate cancer (especially mCRPC) that has certain HRR gene mutations.

PARP inhibitors for metastatic prostate cancer include:

  • niraparib plus abiraterone acetate (Akeega)
  • olaparib (Lynparza)
  • rucaparib (Rubraca)
  • talazoparib (Talzenna)

You can talk with your doctor to learn more about your treatment options, including the benefits and risks of different treatments.

Your outlook with HRR gene-mutated prostate cancer depends on factors such as:

  • the specific gene changes that are present
  • how the cancer responds to treatment
  • whether the cancer has spread outside your prostate

Prostate cancer with HRR gene mutations tends to grow more quickly than prostate cancer without these mutations and is more likely to spread to other parts of your body.

Getting treatment before prostate cancer spreads improves your chances of living longer. Metastatic prostate cancer that has spread cannot usually be cured, but treatment may help slow the growth of the cancer.

You can talk with your doctor to learn more about your condition, treatment options, and outlook.

New treatments may help improve survival and quality of life for people with this condition in the future.

If you have prostate cancer, your doctor might order genetic testing to find out whether you have HRR gene mutations. These mutations limit cells’ ability to repair DNA damage. As a result, they may contribute to cancer growth and spread.

HRR gene mutations can be either germline or somatic. Germline mutations are passed from parents to children and occur in every cell in a person’s body. Somatic mutations occur in one cell and spread when that cell divides.

Treatment of HRR gene-mutated prostate cancer often includes PARP inhibitors, which are targeted therapy drugs that help kill this type of cancer cells. Doctors may prescribe a PARP inhibitor on its own or in combination with other treatments.

You can talk with your doctor to learn more about your condition, treatment options, and outlook. They can help you find out about the latest and most effective treatments.