A Neu Advance in Breast Cancer Treatment

When CalvertHealth Oncology established an internet presence, the principal purpose of this effort was to enhance and extend the ability of the cancer care team to communicate with the people it serves. This blog shares that purpose. Articles I have written over the past several months have addressed many varied subjects related to cancer medicine, but so far I have not been able to impart breaking news about a major, practice-changing development. With today’s entry, that changes.

Last Friday, the fifth of August 2022, the US federal Food and Drug Administration (FDA)approved the use of trastuzumab-deruxtecan, in the form marketed by pharmaceutical company Daiichi Sankyo as Enhertu, in patients with advanced breast cancer whose cancer cells exhibit low-positive test scores for a substance called HER2/neu. The agency based this decision on the findings of the landmark DESTINY-Breast04 trial, which were announced at the national meeting of the American Society of Clinical Oncology (ASCO) in June and published in the New England Journal of Medicine one month ago. Investigators discovered that women whose breast cancer cells had not previously been thought to exhibit enough expression of the HER2/neu marker to allow effective use of the original form of this drug, trastuzumab (Herceptin), experienced a markedly better response to this new combination drug compared to conventional chemotherapy. But what does this mean, and why are oncologists so excited about this development?

In the 1980s and 1990s, researchers in cancer genetics identified a gene called either neu (short for neuroblastoma, the tumor type from which it was first isolated) or Her-2. The protein product of this gene (called HER2/neu, in honor of the underlying gene) spans the cell membrane, making it available as a potential target for drug treatment. Furthermore, in approximately 25% of breast cancers, this protein is overexpressed on tumor cell surfaces, meaning the cell has many, many more copies on display. This characterizes an especially aggressive form of breast cancer, one with a rather grim prognosis. Pathologists score the amount of HER2/neu expression in a particular breast cancer tumor from 0 to 3+. Tumor cells with scores of 3+ and certain ones with scores of 2+ (further studied for overexpression using a type of testing called FISH) are called positive, while the others are called negative. For the past 20 years, oncologists have treated breast cancer patients with trastuzumab and related drugs only if their tumor cells test positive. These anti-HER2/neu drugs turned the prognosis of affected patients on its head—what used to be an adverse finding resulted, when subject to treatment, in markedly improved outcomes. Trastuzumab (approved over 20 years ago, marketed as Herceptin) became a paradigm-shifting drug and ushered in a new era of cancer treatment.

That has now changed. Enhertu applied to patients with advanced breast cancer whose cells test “low-positive” (1+ and 2+, not amplified on FISH) conferred a large, statistically significant benefit in standard survival outcomes above and beyond what we typically see with older-style chemotherapy drugs. Many more women and men with breast cancer will now have the advantage of anti-HER2/neu therapy. I have already gone back into the records of breast cancer patients struggling with advanced disease and the rigors of chemotherapy and found test results that will qualify them for Enhertu.

Another new age in breast cancer treatment has dawned. An old dog has learned a new trick. No one misapprehends Enhertu as the long-sought cure for advanced breast cancer. But it will carry us a long way down that road.