Understanding triple-negative breast cancer to develop better treatments

Breast cancer affects 1 in 8 women in her lifetime. Among the various types, triple-negative breast cancer is the rarest and most aggressive – affecting about 15 percent of breast cancer patients. It is also the least studied.

"If we look at how we define this type of cancer, we define it by what it is not. And when you define something by what it is not, it's harder to treat," said Priyanka Sharma, MD, an oncologist studying triple-negative breast cancer at The University of Kansas Cancer Center in Kansas City. "Once we know what it is, we can develop better treatments for those types of cancers."

Breast cancer can be classified in many ways, depending on the specific cause(s) and stage, but usually falls within one of four subtypes.

  • Endocrine receptor-positive: This accounts for about 70% of all breast cancers and grows in response to estrogen or progesterone hormones.
  • HER2 positive: About 15 percent of breast cancer cases are HER2 positive. This means that the cancer cells make too much of a protein called HER2.
  • Triple-positive: A triple-positive breast cancer diagnosis means that the cancer cells test positive for estrogen or progesterone receptors, and also HER2 protein.
  • Triple-negative: Women whose cancer cells test negative for estrogen receptors, progesterone receptors and HER2 are said to have triple-negative breast cancer. This means that the growth of this cancer is not supported by estrogen, progesterone or the HER2 protein.

Compared to other types of breast cancer, triple-negative breast cancer grows faster, is more likely to return after treatment and has a poorer prognosis. It more often affects women before age 40 or 50. It's also more common in African American or Hispanic women, or women who carry a BRCA1 gene mutation.

While the approach to treatment is similar to all other forms of breast cancer – surgery, radiation, chemotherapy – targeted drugs like anti-estrogen agents and anti-HER2 drugs that work for the other 3 types of breast cancer won't work for triple-negative breast cancer.

"This cancer needs a more tailored approach than what we have available in clinics currently," Dr. Sharma said. "That's why participating in a clinical trial may offer patients with triple-negative more options."

To better understand the disease and what causes it, Dr. Sharma has spent the last six years gathering clinical information from a registry of about 900 triple-negative breast cancer patients. The idea, she says, is to find better, more personalized treatments for each patient. As one of the leading researchers studying this type of cancer, Dr. Sharma's research tool is unlike anything else in the world.

"This helps us study the cancer better," Dr. Sharma said. "It helps us understand why some women have a good response to regimen A, and some have a good response to regimen B."

Dr. Sharma suggests that triple-negative breast cancer most likely contains many different subtypes, each of which could be targeted with specific treatments once it is better understood. By studying the women in the registry, she hopes to tailor specific cancer treatments based on what works best for each woman.

In the meantime, Sharma oversees multiple clinical trials for women who have triple-negative breast cancer, and she is seeing positive outcomes.

"I think the future is bright," she said. "We are finding more and more therapeutic targets. We hope to one day be able to tell women, 'This is the type of triple-negative breast cancer you have, and this is the treatment that works best for it.' We are getting close to that now."​

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