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Treating Triple-Negative Breast Cancer: Recent Progress and What’s to Come

Several sessions at SABCS highlighted our gains against this aggressive form of breast cancer—and the challenges that still remain

Triple-negative breast cancer (TNBC) gets its name from the fact that it is not driven by breast cancer’s three major molecular markers—estrogen receptor, progesterone receptor, and the HER2 oncogene—that classify breast cancer subtypes, making it untreatable with hormone- or HER2-directed therapies. Though TNBC makes up about 15 to 20 percent of newly diagnosed breast cancers in the U.S., we still have few FDA-approved targeted approaches for patients with this aggressive form of the disease. This is particularly concerning since TNBC disproportionately impacts younger women (those who are premenopausal), those with inherited mutations in the BRCA1 gene, and Black women—a group that has an alarming 40 percent higher rate of breast cancer mortality in the U.S.

This is changing, however, as scientists integrate information about the tumor (particularly changes in genes and proteins) derived from new technologies and identify factors driving tumor growth that are potential targets for precision therapy. We now understand TNBC to be a collection of breast cancers, defined by as many as six molecular classifications with potential targeted treatment approaches. 

This progress and remaining challenges to treating TNBC was a prominent topic at this year’s San Antonio Breast Cancer Symposium, the largest scientific conference dedicated to the disease in the world.

Early-stage TNBC is no longer a death sentence

It was not that long ago—about 25 years—that a HER2-positive breast cancer diagnosis came with a dire prognosis. HER2-targeted therapies, beginning with trastuzumab (Herceptin©), changed HER2 breast cancer into not only a treatable breast cancer, but, in many cases, a curable one. We are not yet there with TNBC, but BCRF investigator Dr. Lisa Carey, an expert in treatment for early-stage TNBC, noted the following milestones in a heavily attended SABCS education session:

  • Ninety-five percent of newly diagnosed TNBC patients have early-stage disease, and based on recent clinical trial results, their five-year disease-free survival is well over 80 percent.
  • Neoadjuvant (presurgical) treatment is becoming standard for early-stage TNBC, and new biomarkers are emerging to help guide treatment decisions. PD-L1, a marker used to predict response to immunotherapy in advanced disease, has been shown to be a more general marker for response to chemotherapy in the neoadjuvant setting. Immune markers such as PD-L1 and tumor infiltrating lymphocyte immune cells may someday help doctors personalize treatment based on a patient’s risk of recurrence.

Patients are living longer with advanced TNBC

In spite of encouraging progress, about 20 percent of patients diagnosed with early-stage TNBC will experience a relapse, but as Dr. Rebecca Dent of Singapore National Cancer Center explained at SABCS, patients are living longer. With the help of emerging new treatments, such as PARP inhibitors, immunotherapies, and novel combinations, as well as advances in biomarkers to guide treatment decisions, the median overall survival for advanced or metastatic TNBC has doubled from 12 months to 24 months.

What’s on the horizon

Unlike HER2-positive breast cancer, TNBC is not driven by a single pathway or oncogene, so achieving the game-changing success of trastuzumab in HER2-positive breast cancer will not involve a single class of drugs. Several new approaches are being tested in patients with TNBC now (read recent updates from TNBC clinical trials here). Results from ongoing trials will inform new laboratory research and future clinical trials. New multi-omic technologies will continue to accelerate our understanding of TNBC and transform it from an orphan disease to a defined group of diseases with rational treatment options for each patient.

Read more of BCRF's SABCS 2020 coverage here.

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