BRCA Mutation Predicts Carboplatinum Response in Women with TNBC

Anthony M Magliocco MD

 

A recent study published in Nature Medicine reports that women with triple negative breast cancer with a BRCA mutation were much more likely to respond to treatment with carboplatin compared to treatment with docetaxel, which is the current treatment recommendation for these patients.

https://www.nature.com/articles/s41591-018-0009-7

Triple negative breast cancer remains a difficult disease to treat as standard anti-estrogen or anti-HER2 treatments are not considered.

In this study there were 376 women with advanced triple-negative breast cancer across the trial, regardless of BRCA gene status, the researchers found the 2 drugs worked similarly well. But among the 43 women in the study who also had BRCA gene mutations those who received carboplatin were twice as likely to respond to therapy as those given docetaxel.

The researchers have reported an observed resesponse of 68% of the patients treated with carboplatin, but only in 33% of the women on docetaxel.

 

 

 

Furthermore Carboplatin also appeared to cause fewer side effects along with prolonged tumor progression for longer in women with BRCA mutations—with a progression free survival of  7 months compared with 4 months for those treated with standard docetaxel.

The researchers believe carboplatin is more effective for this patient group because it works by damaging tumor DNA, and BRCA mutations impair the ability of cancer cells to repair the type of DNA damage created by this kind of platinum drug.

This study further highlights the need for availability of BRCA gene testing in women with breast cancer.

This study further highlights the need for NGS gene testing in women with breast cancer for the purpose of appropriate therapy selection

 

One curious feature of the study was women with BRCA1 gene methylation, low BRCA1 mRNA expression, or Myriad HRD analysis was not clearly associated with benefit of treatment with platinum based agents.

 

A study at the Moffitt Cancer Center recently showed many triple negative breast cancers may actually be misclassified due to errors in primary pathology biomarker analysis.

Second opinion analysis should be considered for women diagnosed with triple negative breast cancer as the original biomarker analysis may frequently be flawed and an actionable target such as estrogen receptor or HER2 is identified on reanalysis

 

TRIPLE NEGATIVE BREAST CANCER IS OVER DIAGNOSED

 

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