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Newly developed tumor test may identify more BRCA-like breast cancers


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PARP inhibitors are a new type of cancer treatment developed for patients who have BRCA mutations. The FDA has approved three PARP inhibitors for treatment of ovarian cancer. These medications are also being studied for treating breast cancer in people with BRCA mutations. Researchers believe that these medications may also work well for breast cancer patients whose tumors have features similar to BRCA tumors; this current study describes a new screening tool that may help health care providers find those tumors. Related clinical trials involving PARP inhibitors are ongoing. (6/2/17)


STUDY AT A GLANCE

This study is about:

Development of HRDetect, a test that looks at tumor tissue to determine whether a breast cancer tumor has similar features to breast cancers in people with an inherited BRCA mutation.

Why is this study important?

PARP inhibitors are a new type of cancer treatment developed for patients who have an inherited BRCA mutation. Three PARP inhibitors have already been approved by the FDA to treat ovarian cancer. These medications are also being studied for treating breast cancer in people with BRCA mutations with promising results. Researchers believe that these medications may also work well for other breast cancer patients who do not have an inherited BRCA mutation. This study is about development of a tumor test that can help identify other breast cancer patients who might benefit from PARP inhibitors. 

Only about 1-5% of all breast cancers are the result of an inherited BRCA mutations. However, researchers believe that PARP inhibitor treatment can also benefit patients who do not have an inherited BRCA mutation but do have breast cancers with features that are similar to BRCA breast cancers. This study aims to develop a screening tool to find these BRCA-like cancers. Identification of BRCA-like cancers could help predict which patients may respond well to PARP inhibitor treatment.

Study findings: 

  1. Of 560 breast cancer tumors, the HRDetect screening tool identified 124 with BRCA-like features:
    • 22 were from known BRCA mutation carriers
    • 33 were from patients with an inherited BRCA mutation who did not know their BRCA mutation status prior to this study
    • 22 were from patients who tested negative for an inherited BRCA mutation, but had a BRCA mutation in their tumor
    • 47 were from patients with no inherited or tumor BRCA mutation

What does this mean for me?

Developing a tool to predict which tumors may respond to PARP inhibitors will allow more patients to benefit from this promising treatment. However, the findings in this study do not change current treatment plans. Although research on PARP inhibitors has been promising, none have yet received FDA approval for treating breast cancer. And more research will be needed before HRDetect is available to patients. In the meantime, breast cancer patients should work with their health care providers to determine what treatment plan is best for them.

Questions to ask your health care provider:

  • I carry a BRCA mutation; do I qualify for a clinical trial for PARP inhibitor treatment?
  • Should I consider genetic testing for mutations in BRCA or in other genes that increase my cancer risk?
  • How will knowing if I have a mutation in BRCA affect my treatment decisions and eligibility for clinical trials?

IN-DEPTH REVIEW OF RESEARCH

Study background:

PARP inhibitors are targeted therapies that have been approved by the FDA for ovarian cancer treatment; they are also in clinical trials for treating breast cancer in men and women with BRCA mutations. Research shows that there are some cancers in people, who do not have BRCA mutations in their tumors, that have characteristics similar to breast cancers that do have BRCA mutations in their tumor. Researchers believe these cancers are also candidates for PARP inhibitor treatment. Because of this, Helen Davies, Dominik Glodzik and colleagues from the Wellcome Trust Sanger Institute in the UK and other institutions published work in Nature Medicine in March 2017, showing results from the HRDetect screening tool that they developed to identify other breast cancers with BRCA-like features.

Researchers of this study wanted to know:

Can the HRDetect screening tool identify tumors that have similar features to breast cancers in patients with known germline BRCA mutations?

Population(s) looked at in the study:

This study included 556 females and 4 males with breast cancer. It did not specify type or stage of breast cancer.

Study findings: 

  1. Of 560 breast cancer tumors, the HRDetect screening tool identified 124 of 560 breast cancers that had BRCA-like features:
    • 22 were from patients with a known BRCA mutation
    • 33 were from patients with an inherited BRCA mutation who did not know their BRCA mutation status prior to this study
    • 22 were from patients who had BRCA mutations only in their tumor (no inherited BRCA)
    • 47 were from patients with no inherited or tumor BRCA mutation

Limitations:

While the researchers in this study demonstrated that their screening tool can detect other tumors that may respond well to PARP inhibitors, they do not know if:

  • their screening tool identified all tumors that would respond well to PARP inhibitors
  • the tumors detected by the screening tool would respond well to PARP inhibitors (patients with these tumors did not receive PARP inhibitors as part of their breast cancer treatment)

Also, it is important to note that PARP inhibitors are not yet approved for use in any breast cancer.

Conclusions:

This study suggests that HRDetect can find breast cancers in patients who do not have BRCA mutations, but who may respond well to PARP inhibitors. In addition, HRDetect identified patients who had unknown germline BRCA mutations.  However, PARP inhibitors have not yet been shown to be effective in BRCA-like breast tumors, so more work needs to be done before this screening tool can be reliably used to identify patients that may benefit from PARP inhibitor therapy. 

Posted 6/2/17

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References

Davies H, Glodzik D, Morganella S, et al. “HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures.” Nature Medicine. 2017; 23(4): 517-525.  

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