New Compound Holds Promise for Most Aggressive Triple-negative Breast Cancer

New Compound Holds Promise for Most Aggressive Triple-negative Breast Cancer

In just under four years, researchers have identified the gene involved in the development of metaplastic breast cancer — the most aggressive type of triple-negative breast cancer — and advanced a potential treatment for the disease to clinical trials.

The findings, in a study titled “Role of RPL39 in Metaplastic Breast Cancer,” were published in the Journal of the National Cancer Institute.

“We not only uncovered the biological pathway stimulating cancer growth, but we found a compound that blocked it, increasing the survival of mice carrying human metaplastic breast tumors,” Jenny C. Chang, MD, director of the Houston Methodist Cancer Center, and the study’s senior author, said in a news release.

While metaplastic breast cancer accounts for less than 1 percent of all breast cancer, it is the most aggressive type of triple-negative breast cancer, and the odds of patients surviving are low.

A key reason is that metaplastic tumors are highly unresponsive to chemotherapy.

Only 40 percent of those who get the disease survive for three years. The survival rate for triple-negative breast cancer patients as a whole is 70 percent.

Triple-negative cancers test negative for estrogen receptors, progesterone receptors, and HER2. If a cancer has any of the receptors, it can be targeted with hormone therapies that block the pathways the receptors activate.

Triple-negative breast cancers are unresponsive to hormone therapy, so doctors treat them with a combination of surgery, chemotherapy, and radiation therapy.

Researchers found that 39 out of 40 metaplastic breast patients have a mutation in their RPL39 gene that promotes tumors in the same way HER2 does. The mutated RPL39 cells divide uncontrollably, sparking tumor growth.

The identification of the mutation, which is common in virtually all metaplastic breast cancers, led the researchers to hypothesize that blocking the RPL39 pathway could prevent tumor growth.

The team discovered that RPL39 activated a protein called inducible nitric oxide synthase (iNOS). When levels of both proteins were elevated, patients had lower survival rates. This prompted the researchers to think that blocking iNOS would be a way to treat metaplastic breast cancer.

They found that L-NMMA, a compound that inhibits iNOS, reduced tumor volume in metaplastic breast cancer mouse models. They also learned that a combination of L-NMMA and Taxol (docetaxel), a chemotherapy drug, reduced tumor volume more than Taxol alone.

“The results showed elimination of the cancer in nearly all of the mice when combined with standard chemotherapy,” said Chang, who is also a professor of medicine at Weill Cornell Medicine. “Our goal is to turn metaplastic breast cancer from a debilitating disease into a chronic illness.”

L-NMMA will now be assessed in a Phase 1 trial of metaplastic breast cancer patients. The study, which is currently enrolling patients, will be conducted at Houston Methodist Hospital.



  1. michelle Bleicher says:

    I have been diagnosed with Metaplastic Breast Cancer. I have been treated with more than one kind of chemotherapy: adriamycin and cytoxin with the tumor growing in size, taxotere, carboplatin, herceptin, perjeta with awful diarrhea, taxotere, carboplatin and herceptin with little shrinkage of the tumor, with the newest regiment starting this Friday with taxol and carboplatin. We have now reached the point where surgery is scheduled for May 1. Can I communicate with someone about my disease? Can someone call me? 954 234 0728

  2. Lisa says:

    Hello Michelle, have you received the surgery for MBC? I was also diagnosed with MBC last fall (2018). I had a partial mastectomy, with no followup treatment. Not to scare you, but my husband and I have decided against followup treatment, as MBC appears to be chemoresistant and the triple negative means that the hormone therapy also wouldn’t help. I have had many people praying for me and I believe God has led us to the right decision. We are trusting Him for His healing that only He can give. I will be praying for you, as well – Lisa.

  3. Tessa Sendejas says:

    I was diagnosed with Metaplastic Breast Cancer on 8/22/18 & had it removed (lumpectomy) on 8/30/18. Although there was no lymph node involvement my surgeon removed a sentinel node and one behind as a precaution. I don’t read much about survival rates for women who have surgery first to have the tumor removed. Shouldn’t this be considered since these tumors are chemo resistant? I am now going through the chemo protocol (taxol & AC) and will follow up with radiation afterward. My Ki67 was at 50% so the tumor was aggressive yet I was asked to leave it in to receive chemo. I refused since there is no guarantee chemo would work and I could not risk having it consume my body.

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