HER2 in Breast Cancer: Shaping Treatment in Other Solid Tumors

Dr. Ritu Salani and Dr. Martin Dietrich continue their discussion on HER2-directed therapies across various malignancies. They focus on the lessons learned from breast cancer and the potential implications for other tumor types.

Dr. Dietrich explains that in breast cancer, the focus has shifted from HER2 amplification as the core driver to a broader spectrum, including HER2 expression levels determined by immunohistochemistry (IHC). This shift has influenced the diagnostic approach in breast cancer and other cancers. While HER2 amplification was traditionally assessed by in situ hybridization, IHC is now being prioritized as a pan-cancer tumor marker. The different expression levels (0 to 3+) may play a prognostic role, even in HER2-low and HER2-negative disease, where lower levels of HER2 expression may still be sufficient for delivering antibody-drug conjugates (ADCs) to the tumor microenvironment.

Dr. Salani shares her experience with gynecologic cancers, noting that somatic mutations were previously used in cervical cancer, resulting in mediocre response rates. In endometrial cancer, IHC testing similar to breast cancer was used, with 3+ considered positive and requiring FISH confirmation. HER2 expression rates in gynecologic malignancies are not well-established due to inconsistent testing, but estimates range from 5% in cervical cancer to 15-30% in uterine cancers and 10-15% in ovarian cancer.

The DESTINY-PanTumor study, which used gastric testing, has generated excitement in the gynecologic oncology community. Standardizing testing across tumor sites is crucial for understanding when to use HER2-targeted agents. While exploratory use of therapies is common when options are limited, consensus testing and standardization are still needed to guide treatment decisions.

Summary generated by Claude AI.