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Abnormal BRCA1 Gene Linked to Worse Outcomes Than Abnormal BRCA2 Gene

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A study suggests that women who have an abnormal BRCA1 gene and are diagnosed with breast cancer have worse survival and recurrence (the cancer coming back) rates than women with an abnormal BRCA2 gene or women who don’t have either abnormal gene.

The study was presented at the 2013 American Association for Cancer Research Annual Meeting. Read the abstract of “Breast cancer survival of BRCA1/2 carriers compared to non-BRCA1/2 carriers in a large breast cancer cohort.”

Most inherited cases of breast cancer are associated with one of two abnormal genes: BRCA1 (BReast CAncer gene one) or BRCA2 (BReast CAncer gene two).

Women with a BRCA1 or BRCA2 genetic mutation:

  • have up to a 72% lifetime risk of developing breast cancer
  • have a much higher-than-average lifetime risk of ovarian cancer; estimates range from 17% to 44%

In this Dutch study, researchers looked at information on BRCA1 and BRCA2 status, recurrence rates, and survival rates from 5,518 women diagnosed with breast cancer before age 50. About 3.6% of the women had an abnormal BRCA1 gene and about 1.2% of the women had an abnormal BRCA2 gene.

After 15 years of follow-up, the researchers found that women with an abnormal BRCA1 gene were:

  • 1.5 times more likely to have the breast cancer come back (recurrence)
  • 1.4 times more likely to die from breast cancer

compared to women who didn’t have an abnormal BRCA1 gene.

Women who had an abnormal BRCA2 gene and women who didn’t have either of the two abnormal genes had about the same survival rates.

The three groups of women also were diagnosed with different cancer types:

  • 29% of women with an abnormal BRCA1 gene had estrogen-receptor-positive cancer
  • 86% of women without an abnormal BRCA gene had estrogen-receptor-positive cancer
  • 81% of women with an abnormal BRCA2 gene had estrogen-receptor-positive cancer

It’s not clear why women with an abnormal BRCA1 gene have worse outcomes than women with an abnormal BRCA2 gene or women without either abnormal gene. It could be in part because women with an abnormal BRCA1 gene tend to have more hormone-receptor-negative breast cancers, which tend to have a worse prognosis than hormone-receptor-positive breast cancers. This is partially because hormonal therapy medicines are prescribed after surgery to reduce the risk of hormone-receptor-positive cancers coming back.

Right now, breast cancers are treated based on cancer characteristics such as size, hormone-receptor status, HER2 status, and cancer stage. BRCA status isn’t considered. The researchers think that BRCA1 and BRCA2 status might turn out to be important to consider when planning breast cancer treatment. Still, more research needs to be done before doctors know exactly how BRCA1 and BRCA2 status affect breast cancer prognosis and treatment outcomes.

You can learn more about abnormal BRCA1 and BRCA2 genes and steps women with an abnormal gene can take to lower their risk on the Risk Factors: Genetics page.

Editor’s Note: This article was updated on Jan. 24, 2019, with updated information on cancer risk associated with BRCA mutations.

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