An NCI-designated Comprehensive Cancer Center
By Kevin Chesley | October 2, 2018
City of Hope is a founding beneficiary of the Pink Patch Project, an innovative public awareness campaign designed to bring attention to the fight against breast cancer and to support cancer research organizations. Throughout October, which is Breast Cancer Awareness month, we’ll be sharing important information on the progress we’re making in combating this devastating disease. Learn more about the Pink Patch Project here.
One of the most challenging forms of breast cancer is called metastatic triple negative. Yuan Yuan, M.D., Ph.D., an assistant professor specializing in breast oncology in the Department of Medical Oncology & Therapeutics at City of Hope, knows that those faced with metastatic triple-negative breast cancer have a tough fight ahead of them, but she is working to make that battle more surmountable.

The Three Negatives

The name comes from a lack of three different receptors on the breast cancer cells: estrogen receptors, progesterone receptors and HER2 (human epidermal growth factor) receptors. Since hormones are not supporting its growth (unlike other forms of breast cancer), this type of cancer is unlikely to respond to hormonal therapies. Triple-negative breast cancer also is unlikely to respond to medications that target HER2. “Triple-negative breast cancer is one of our most challenging and aggressive diseases,” Yuan explains. “The tumor is characterized by dividing really fast. It grows and proliferates with a higher chance of metastases, spreading beyond the local and into the liver, lung and brain — the really vital organs that we survive on.”

The Importance of Genetic Counseling

It also has a genetic component that, according to Yuan, makes early detection more important. “It happens more among certain ethnic backgrounds, such as African-Americans and Hispanics. Also in younger women. I would encourage anyone who has a family history of early-onset breast cancers to look into genetic counseling,” she says. “Triple-negative breast cancer has a connection to the BRCA1 mutation, and nowadays our more comprehensive genetic testing panels are able to identify gene mutations beyond BRCA1 and 2.” 

Treatment Options and Research

Yuan believes the cure lies beyond standard chemotherapy. “Unfortunately, there is no FDA-approved target therapy beyond conventional chemo. But the tumor often becomes chemotherapy-resistant,” she says. “There have been a lot of efforts in research such as identifying newer targets, identification of immunotherapies. At this moment, we have multiple clinical trials utilizing a combination strategy.”
Yuan’s treatment modalities include immunotherapy. “One of the agents being tested is called pembrolizumab, or Keytruda, but the results are not good enough,” she says. “Our patients have a very aggressive disease and need a more effective therapy to relieve symptoms and prolong survival.” 
She is trying everything from AXL stem cell inhibitors to hormone therapy, although the cancer cells’ lack of estrogen and progesterone receptors makes treating with hormones difficult. Finding the right combination will be key: “We are looking at androgen receptors, a male hormone receptor found in 10 percent of triple-negative patients, hoping to see signals,” Yuan says. “Some earlier trials utilized drugs like enzalutamide to treat prostate cancer because the prostate cancer cells expressed androgen receptors. So we are using that concept, but the signal is not super robust. The response rate is around 15 to 20 percent when you are just giving patient hormonal therapy. So, we are combining hormonal therapy, anti-hormonal therapy and anti-androgen receptors with anti-PD1 inhibitors, hoping to see some synergies between these.” 
Yuan knows that time is a factor. “The triple-negative patients have a much higher rate of recurrence, and once patients are diagnosed Stage 4 or metastatic, the overall survival is really pretty bad: about 13 months. Exercise and weight reduction have in some areas shown benefit, but the most important thing is to follow up with your oncologist.”
Though multiple clinical trials have created less-than-ideal results, Yuan believes the answer to shrinking triple-negative tumors involves a combination of methods, including immunotherapy. She encourages any woman diagnosed with metastatic triple-negative breast cancer to consider becoming part of one of the clinical studies at City of Hope. When it comes to finding the answer to this aggressive disease, any test subject could prove to be the positive answer.
Learn more about our breast cancer program and treatments. If you are looking for a second opinion about your breast cancer diagnosis, please call 800-826-4673 or fill out the online appointment form .

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