Advanced-Stage, Triple-Negative Breast Cancer in Women With BRCA1/2 Mutation Seems to Respond Better to Carboplatin Than Taxotere

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Triple-negative breast cancer is:

  • estrogen-receptor-negative
  • progesterone-receptor-negative
  • HER2-negative

About 15% to 20% of breast cancers are triple-negative. Triple-negative cancers usually are more aggressive, harder to treat, and more likely to come back than cancers that are hormone-receptor-positive and/or HER2-positive. Hormonal therapy and targeted therapies such as Herceptin (chemical name: trastuzumab), Tykerb (chemical name: lapatinib), Perjeta (chemical name: pertuzumab), and others that target the HER2 receptor don't work on triple-negative breast cancer.

Locally advanced-stage breast cancer is breast cancer that has spread to tissue near the breast, but not to parts of the body away from the breast. Metastatic breast cancer is advanced-stage cancer that has spread to parts of the body away from the breast -- the bones, liver, or brain, for example.

Advanced-stage, triple-negative breast cancer is usually treated with chemotherapy, but response rates have been lower than doctors would like.

A study suggests that women diagnosed with advanced-stage, triple-negative breast cancer who also have a BRCA1 or BRCA2 mutation have a better response to a chemotherapy regimen that includes carboplatin than a regimen that includes Taxotere (chemical name: docetaxel).

The research was published in the April 30, 2018 issue of Nature Medicine. Read the abstract of “Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.”

Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two). Women with a mutation in the BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by age 70. Their risk of ovarian cancer also is higher than average. Men with an abnormal BRCA gene have a higher risk of both breast and prostate cancer.

DNA carries genetic information in both healthy cells and cancer cells. Cells can develop DNA damage spontaneously or from exposure to specific things in the environment (too much sun, for example) that make DNA damage more likely to happen. But cells can detect and repair damage to DNA. When DNA is damaged in a healthy cell and the damage isn't fixed, that cell can become cancerous. Mutated BRCA1 and BRCA2 genes are thought to increase the risk of breast and other cancers because these abnormal genes interfere with cells' ability to repair damaged DNA.

Carboplatin is a platinum-based chemotherapy medicine. Platinum-based chemotherapy weakens or destroys breast cancer cells by damaging the cell’s DNA and making it harder for the cell to repair DNA damage.

Taxotere is a taxane chemotherapy medicine. Taxane interferes with the ability of cancer cells to divide.

Because advanced-stage, triple-negative disease doesn’t always respond to standard chemotherapy regimens that include a taxane, such as Taxotere, researchers wondered if using a platinum-based chemotherapy like carboplatin would offer more benefits than Taxotere, especially in women with a BRCA1 or BRCA2 mutation. They wondered this because a mutated BRCA1 or BRCA2 gene makes it harder for a cell to repair DNA damage and platinum-based chemotherapy, such as carboplatin, damages a cancer cell’s DNA.

To do the study, the researchers randomly assigned 376 women diagnosed with advanced-stage, triple-negative breast cancer to either treatment with carboplatin (188 women) or Taxotere (188 women).

Overall, there was no difference in response to the medicines -- both seemed to work equally well.

But when the researchers looked specifically at 43 women in the study who had a BRCA1 or BRCA2 mutation, they found that these women were twice as likely to respond to carboplatin as they were to Taxotere:

  • 68% of women with a BRCA1/2 mutation treated with carboplatin saw the cancer shrink
  • 33% of women with a BRCA1/2 mutation treated with Taxotere saw the cancer shrink

Compared to Taxotere, carboplatin also stopped the breast cancers in women with a BRCA1 or BRCA2 mutation from growing for a longer period of time -- 7 months compared to 4 months for Taxotere -- and also caused fewer side effects.

The researchers believe that carboplatin is more effective than Taxotere in women with a BRCA1 or BRCA2 mutation because carboplatin damages the cancer’s DNA and the mutated BRCA1 or BRCA2 gene can’t fix the damage.

"Our study has found that women with triple-negative breast cancer who have BRCA1 or BRCA2 mutations are twice as likely to respond to carboplatin as they are to standard treatment," said Dr. Andrew Tutt, of the Institute of Cancer Research in the United Kingdom, in a statement. "It strongly suggests that many women with triple-negative breast cancer should be considered for testing for faults in the BRCA genes so those who test positive can benefit from carboplatin. Using this simple test enables us to guide treatment for women within this type of breast cancer. I am keen for these findings to be brought into the clinic as soon as possible."

"Women with a BRCA1 or BRCA2 mutation who have been diagnosed with advanced-stage, triple-negative breast cancer will be more likely to get carboplatin earlier in their treatment plans now," said Brian Wojciechowski, M.D., Breastcancer.org’s medical adviser.

If you’ve been diagnosed with advanced-stage, triple-negative breast cancer and know you have a BRCA1 or BRCA2 mutation, you might want to talk to your doctor about this study.

If you’ve been diagnosed with advanced-stage, triple-negative breast cancer and have not had genetic testing to find out if you have a BRCA1 or BRCA2 mutation, you might want to talk to your doctor about this study and ask if genetic testing makes sense for your unique situation.

You and your doctor will develop a treatment plan for the cancer that will likely include chemotherapy. If you know you have a BRCA1 or BRCA2 mutation and carboplatin is not part of your chemotherapy regimen, you may want to ask why. No matter which treatments are recommended for you, you may want to talk to your doctor about:

  • why each treatment is recommended (including any combinations)
  • treatment timing and sequence
  • the expected benefits, risks, and side effects of each treatment

For more information, visit the Breastcancer.org pages on Triple-Negative Breast Cancer as well as our pages on Genetic Testing.

To connect with others managing a triple-negative breast cancer diagnosis, join the Breastcancer.org Discussion Board forum Triple-Negative Breast Cancer.


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