TNBC Awareness Day Emphasizes Progress in Treatment Strategies

Treatment options have historically been limited in the triple-negative breast cancer (TNBC) armamentarium, and although the landscape has evolved with a variety of treatment strategies including antibody-drug conjugates (ADCs) and chemoimmunotherapy, additional therapies could help improve outcomes for this patient population, according to Angela Jain, MD.

Of note, the FDA approved sacituzumab govitecan-hziy (Trodelvy) in April 2021 for the treatment of patients with unresectable locally advanced or metastatic TNBC who were previously treated with 2 or more systemic therapies, with at least 1 prior treatment for metastatic disease.1 Later in July 2021, the FDA approved neoadjuvant pembrolizumab (Keytruda) plus chemotherapy, followed by pembrolizumab monotherapy, for the treatment of patients with high-risk, early-stage TNBC.2

“Unfortunately, TNBC is a more aggressive type of breast cancer,” Jain explained in an interview with OncLive® during TNBC Awareness Day. “Although these new, novel treatments are doing better than the previous standard of care, they're still not perfect.”

In the interview, Jain discussed the existing and available treatment options in the TNBC landscape, ongoing clinical studies, and challenges and unmet needs that persist in the TNBC treatment paradigm.

Jain is an associate professor in the Department of Hematology/Oncology and interim chief in the Division of Breast Medical Oncology at the Fox Chase Cancer Center in Philadelphia, Pennsylvania.

OncLive: Why is raising awareness about TNBC crucial?

Jain: TNBC is a breast cancer that is more aggressive than some of the other types, and it's important to get the word out, as we're trying to make sure that all of our patients are keeping up with their screening and know about signs and symptoms to look out for.

What is the current state of the TNBC treatment armamentarium?

In TNBC, we use different agents. Some of them are considered chemotherapy, some are targeted therapies, and some are more along the lines of immunotherapy. We are now using pembrolizumab, either in the [perioperative] setting or the metastatic setting. We're also using sacituzumab govitecan in patients with metastatic disease. That's an example of a more targeted chemotherapy approach. There's also targeted therapy like olaparib [Lynparza], which [could be used in select patients] either after surgery or sometimes in the metastatic setting.

[Regarding novel agents], in the neoadjuvant and adjuvant setting, we're looking at different agents that are more targeted or in combination with chemotherapy or immunotherapy, and then the same thing in the setting of metastatic disease. There are several of these trials going on right now.

How have PARP inhibitors, such as olaparib, emerged in this treatment paradigm?

Patients who have a BRCA mutation are eligible to receive olaparib. They either found out that they have an inherited mutation from their parents, or in patients where the tumor itself showed a BRCA mutation, maybe [that was seen in] genetic testing. [Olaparib is part of] a class of drugs called PARP inhibitors, and these drugs work best in patients with a BRCA1 or a BRCA2 mutation. We use these drugs either in the adjuvant setting for some patients, but also in the metastatic setting.

What are some clinical studies that are either ongoing or on the rise for TNBC?

The most interesting data that have come out is looking at patients who actually have HER2-low disease; [these] patients may have been previously designated to have HER2-negative breast cancer, but we now know that there's a different category that we can call HER2-low, and these patients can still benefit from fam-trastuzumab deruxtecan-nxki [Enhertu]. In my experience, this drug has been quite active.

There are also [other] ADCs, which are the newer, up-and-coming drugs. [A particular one is] datopotamab deruxtecan [Dato-DXd; Datroway], and we're looking forward to seeing how that is going to come into play for patients with TNBC. We've seen this drug already in clinical trials and at multiple institutions around the world, including Fox Chase Cancer Center.

What are some ongoing challenges and unmet needs within the TNBC treatment paradigm?

We’re still trying to understand how to optimize treatment for TNBC, which is still something that needs to be researched, whether it's [considering the] combination of drugs or developing novel drugs. There's [also] a possibility that not all TNBCs are the same. One example I can provide is there is a new paradigm in thinking about HER2-positive disease, and some patients could be considered HER2-low. For patients who are diagnosed with TNBC [who may] have HER2-low disease, they may still be eligible for some newer targeted agents in the HER2-positive realm.

References

1. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. FDA. Updated April 8, 2021. Accessed February 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer
2. FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer. FDA. Updated July 27, 2021. Accessed February 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-high-risk-early-stage-triple-negative-breast-cancer