The first FDA approval for immunotherapy in metastatic TNBC arrived in 2019, and subsequent approvals continue to expand options for metastatic patients-depending on the presence of an important immune marker called PD-L1 in their tumors-and early-stage patients. Checkpoint inhibitors, which are designed to activate immune cells, were practice changing for TNBC when combined with chemotherapy. Immunotherapy: Over the last decade, many researchers shifted their focus from targeting cancer cells to leveraging the immune system to eradicate tumors.Two therapies, talazoparib ( Talzenna®) and olaparib ( Lynparza®), were approved for metastatic, HER2-negative breast cancer in 2017-2018, and recent findings presented at the American Society of Clinical Oncology’s annual meeting in 2021 showed their immense promise in patients with early-stage (pre-surgical) TNBC as well. These drugs inflict catastrophic DNA damage on cancer cells that lack functional BRCA1 or BRCA2, which are DNA repair genes. PARP inhibitors: People with TNBC who have inherited mutations in a BRCA gene (approximately 15 percent of patients) may be treated with PARP inhibitors.Among them are these FDA-approved drugs for triple-negative breast cancer: Recently though-as more sophisticated analytical technologies, exciting discoveries in the broader cancer field, and new drugs emerged-the limited toolbox of options for treating TNBC has expanded to an arsenal of options. But all the while, researchers continued refining chemotherapy-testing different types of chemo drugs, trying new combinations, providing it to early-stage patients before surgery-and response rates did improve. This makes targets even harder to pin down, and a few trials assessing targeted therapies failed in the 2010s. What they learned is that this catchall subtype of breast cancer can differ widely from patient to patient and adapt to resist therapies. Over the years, as molecular sequencing and analysis technologies advanced, scientists doggedly probed TNBC for new therapeutic targets. While the latest chemotherapy drugs for breast cancer are highly effective at killing tumor cells and have saved millions of lives, they are also characterized by their toxic side effects, as they can affect some healthy cells throughout the body. Until recently, 10 to 15 percent of breast cancer patients diagnosed with TNBC were restricted to a less-targeted therapeutic mainstay: chemotherapy. And if we take a step back to look at progress in the field over the years, there are new reasons to feel hopeful after looking at recent TNBC news. Inherently, TNBC is more aggressive, tends to be diagnosed at an earlier age than other breast cancers, and is overrepresented among Black patients. Researchers fully understand the urgency of this disease. But as triple-negative breast cancer (TNBC) lacks breast cancer’s three major classifications-ER, PR (progesterone receptor), and HER2-therapeutic targets have been much more difficult to find. By using drugs that specifically block these pathways, the targets became Achilles’ heels and the therapies ultimately proved fatal for most breast cancer cells. Researchers uncovered the right therapeutic targets-molecular processes that cancer cells need to survive-in the estrogen receptor, which drives the growth of ER-positive tumors, and HER2, whose signaling promotes the progression of HER2-positive tumors. Most treatment success stories in breast cancer result from the rational design of therapies.
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