Triple-Negative Breast Cancer: New Treatments Are Changing Outcomes

Triple-negative breast cancer (TNBC) has historically been considered the “bad” girl of diagnoses — the most difficult to treat type of breast cancer, and the one with the poorest survival statistics. But new therapies are changing options for these patients, making it a much more treatable disease — though the advances are too new to reflect that, says Lauren Elreda, MD, director of breast medical oncology at NewYork-Presbyterian Queens Hospital. Recently, Dr. Elreda spoke to us about the latest advances.

Everyday Health: Let’s break it down. Breast cancer is an umbrella term for more than one type of breast cancer, isn’t it?

Lauren Elreda: Yes. There are several different types of breast cancer and within those subtypes, there are variations. One person may have one type of breast cancer as opposed to their neighbor, who may have a different type.

EH: How do you define them?

LE: The types are identified by the biomarkers carried on the surface of the cancer cells. These consist of receptors for estrogen, progesterone, and a protein called HER2 neu. If your cancer expresses biomarkers for estrogen and progesterone, but not HER2, it is referred to as a hormone-positive breast cancer, and hormones are known to stimulate their growth. HER2-positive breast cancer can be either hormone-negative or hormone-positive. If the cancer expresses all three receptors, we call that a triple-positive breast cancer.

EH: What makes triple-negative breast cancer (TNBC) different than other types?

LE: If a breast cancer doesn’t express receptors for estrogen, progesterone, or HER2, the cancer is considered triple-negative.

EH: Can you spell out for us why these biomarkers are so important?

LE: Biomarkers are really important when we’re identifying what subtype of breast cancer a patient has because the treatment varies widely based on them.

EH: TNBC is notoriously more difficult to treat. Why?

LE: TNBC tends to behave aggressively. Standard treatments are limited here because we are not able to block hormones or HER2 pathways.

EH: Who is most at risk for TNBC?

LE: Triple-negative can occur in anyone, but tends to present in younger women, women under the of age 40, women who are Black or Latina, and women who may have the BRCA1 or BRCA2 mutations, which is an inherited gene passed down from a patient’s mother or father that puts them at increased risk for developing breast cancer. About 15 percent of those with a BRCA mutation present with triple-negative disease. There may be a correlation between those mutations and TNBC.

EH: Are screening guidelines sufficient to catch those at highest risk?

LE: The screening guidelines in place for breast cancer are the same regardless of the type of breast cancer we’re talking about. The thing that changes screening is whether you have a primary relative affected by breast cancer. If a relative has been diagnosed with breast cancer, whether it was triple-negative or not, we’d start screening that person’s relative ten years earlier. If a mother was diagnosed at age 40, for instance, we’d recommend the daughter start screening at age 30. That’s because those with a strong family history of breast cancer or have the BRCA1 or BRCA2 mutation are considered high risk for developing breast cancer. Earlier screening is advised to detect and cure breast cancer early, if it develops.

EH: Does TNBC tend to run in families, like the BRCA mutations?

LE: The answer is no. We have patients in the same family with different types of breast cancer. It’s not considered an inherited type of breast cancer, but, as I said, it can be associated with a BRCA mutation, which does run in families.

EH: Can other subtypes of breast cancer morph into TNBC?

LE: Changing of biomarkers usually happens in the setting of a recurrence of the original breast cancer. In those cases, it’s imperative that a biopsy is taken to make ensure that the biomarkers have not changed. It will be important to what treatment strategy is applied to that patient.

EH: TNBC has, historically, been considered a grim diagnosis. Is that changing?

LE: We do have a better outlook as there are more treatments available to offer. The statistics for long term outcomes may lag as new treatments are approved.

EH: Walk us through it. What was the first breakthrough?

LE: Immunotherapy. In breast cancer, it was first shown to work in advanced TNBC. If a biomarker called PDL1 is present on the TNBC tumor cells, these patients tend to be more sensitive to immunotherapy. Immunotherapy utilizes a patients’ own immune cells to recognize and attack the cancer. Immunotherapy in combination with chemotherapy has also been approved in treating potentially curable patients before surgery. This was shown in a clinical trial known as Keynote 522, and published in The New England Journal of Medicine. Immunotherapy has been revolutionary for cancer. We can only get better from here.

EH: Trodelvy was a new recent advance, wasn’t it?

LE: Trodelvy is a different type of medication that is considered an antibody drug conjugate therapy. It’s an antibody that has a drug attached to it that attaches to cancer cells and the drug becomes internalized into the cancer cells and kills it from the inside. It’s approved in advanced TNBC. It’s usually given if a patient’s disease progresses on immunotherapy (if a patient was a candidate for it). It’s also recently been approved for patients with hormone-positive breast cancer who have advanced disease.

EH: Are there different side effect profiles for these drugs than standard chemotherapy?

LE: Immunotherapy in general is well tolerated, however the immune system can become so enhanced from immunotherapy that people can develop side effects that can mimic autoimmune side effects. For instance, inflammation of the colon, skin, or lungs. We educate patients of these possibilities and to report, rash, diarrhea, or shortness of breath or cough. Patients on chemotherapy or medications like Trodelvy, in general, may have some nausea, fatigue, or loose stools, and we may see a lowering of their white blood cell count, which may put them at risk for infections.

EH: Who should seek out a TNBC clinical trial?

LE: Clinical trials are important for TNBC, especially in patients with advanced disease. Patients with advanced TNBC are not considered curable, but they are treatable. It’s always good to be ahead with clinical trials, as there’s a limit to the amount of therapies for TNBC, and we’re always looking at new and novel therapies to treat it. Clinical trials are a chance to understand the science behind the disease. I would always suggest that if the standard therapies aren’t working that we look for a clinical trial.

EH: What would you tell a woman who is newly diagnosed with TNBC?

LE: After explaining their diagnosis, I always look to understand the support system the patient has. That’s extremely important because a patient’s family and friends are vital in their journey. I encourage them to keep a positive state of mind, and tell them we have to take it one step at a time. I tell them to try not to get ahead of themselves, and not to focus on the what ifs, but to focus on nutrition, sleep, and light exercise, and seeking therapy if they need it. Mental health is just as important. I tell them if there's a problem, we’ll try and find a solution. And that’s pretty much how we end our first conversation.

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