Lisa A. Carey, MD

Lisa A. Carey, MD, ScM, the L. Richardson and Marilyn Jacobs Preyer Distinguished Professor for Breast Cancer Research and deputy director of clinical sciences at the University of North Carolina Lineberger Comprehensive Cancer Center, discusses the recent trends in treatment for triple-negative breast cancer (TNBC).

Carey says TNBC has been the hardest subtype of breast cancer to treat, and progress has been slow. However, recently there have been advances in tumor targeting, which was a challenge due to TNBC’s heterogeneity.

Tumor targeting advances include improvements in the application of chemotherapy, along with antibody-drug conjugates such as sacituzumab govitecan (Trodelvy), which has been approved for TNBC, and trastuzumab deruxtecan (Enhertu), which has shown benefit in patients with HER2-low disease in addition to HER2-positive breast cancer. For those with homologous recombination deficiency (HRD), PARP inhibitors are being investigated as a truly tumor-targeted drug, according to Carey.

Immunotherapy has also made an impact, with chemotherapy plus immune checkpoint inhibitor therapy being used in regardless of PD-L1 status in early disease. It is also a preferred frontline therapy for metastatic TNBC in those with high PD-L1 expression, which Carey notes is 40% of those with metastatic disease. The improvements in chemotherapy and immunotherapy are critical for patients as researchers continue to investigate more targeted therapies.

 TNBC has been the hardest for us to actually show any kind of movement and progress in the metastatic setting where the [overall] survival, until recently, was only about 1 to 2 years. The biggest advances have been really in segregating tumor targeting, which is actually pretty hard to do, because TNBC is a bit of a shapeshifter, and it's a very heterogeneous entity.

But the advantages in tumor targeting have come in being better at giving chemotherapy. While we work on truly targeted drugs, we're getting much better given chemotherapy through these antibody-drug conjugates. Things like sacituzumab govitecan and now trastuzumab deruxtecan have really been game-changers in the way we give cytotoxic therapy. I think TNBC is also enriched for those with HRD, and so PARP inhibition—clearly for not just germline, but it looks like somatic 

 mutations and maybe some others that are related—seems to be very helpful. That's our one truly tumor-targeted drug.

The flip side of that is the importance of immunotherapy. So in TNBC, which is the most immune-activated of all the breast cancer kinds, immunotherapy is now standard for early disease. It doesn't require selection for PD-L1 or anything like that. In the metastatic setting…about 40% of breast cancers are PD-L1–positive in the metastatic setting, and those benefit from the addition of immune checkpoint inhibition to chemotherapy. And...I think both of those are game-changers, both the improvements in the way we give chemotherapy, and also the addition of immune checkpoint inhibition.

Videos

Lisa A. Carey, MD, ScM, discusses the recent trends in treatment for triple-negative breast cancer. 

Reviewing the Latest Advancements in Treatment of TNBC

Lisa A. Carey, MD, professor, UNC Lineberger Comprehensive Cancer Center, discusses the CALGB 40502/NCCTG N063H trial in patients with triple-negative breast cancer (TNBC), a randomized phase III trial of paclitaxel compared with nab-paclitaxel (Abraxane) or ixabepilone (Ixempra) with bevacizumab (Avastin) as first-line chemotherapy for locally recurrent or metastatic breast cancer.

There were a few noteworthy findings in the updated results reported at the 2017 San Antonio Breast Cancer Symposium, Carey notes. The original finding of an improvement in progression-free survival with paclitacel or nab-paclitaxel over ixabepilone held true, and this translated into an overall survival advantage.

Lisa A. Carey, MD, professor, UNC Lineberger Comprehensive Cancer Center, discusses the CALGB 40502/NCCTG N063H trial in patients with triple-negative breast cancer, a randomized phase III trial of paclitaxel compared with nab-paclitaxel or ixabepilone with bevacizumab as first-line chemotherapy for locally recurrent or metastatic breast cancer.<br />
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Results of the CALGB 40502 Study in TNBC

Lisa A. Carey, MD, Professor of Medicine, University of North Carolina at Chapel Hill, discusses assays and intrinsic subtypes of breast cancer.

The six intrinsic subtypes of breast cancer are luminal A, luminal B, HER2-enriched, basal-like, normal breast, and claudin-low. Though these subtypes are prognostic, Carey says, the way they inform treatment is a work in progress.

Several assays exist specifically to prognosticate the disease such as the 70-gene MammaPrint and the Oncotype DX Recurrence Score. A number of assays exist, though Carey notes that nothing is valid for ER-, HER2+ disease.

The question remains as to how assays will be assessed regarding the information they give off and how pathways can be put together within a subtype, Carey says. In the future, physicians and researchers will molecularly characterize tumors and then use assays to get better information regarding treatment.

There are six intrinsic subtypes of breast cancer: luminal A, luminal B, HER2-enriched, basal-like, normal breast, and claudin-low

The way intrinsic subtypes inform treatment is a work in progress

Carey believes that, in the future, physicians and researchers will molecularly characterize tumors and then use assays to get better information regarding treatment

Lisa A. Carey, MD | Authors

Articles

Reviewing the Latest Advancements in Treatment of TNBC

Results of the CALGB 40502 Study in TNBC

Assays and Intrinsic Subtypes of Breast Cancer