From studies presented at the San Antonio Breast Cancer Symposium and elsewhere, important observations have emerged that will eventually advance our understanding of HER2-positive disease. According to C. Kent Osborne, MD, of Baylor College of Medicine, Houston, key findings include the following:

• Combinations of trastuzumab (Herceptin) plus pertuzumab or lapatinib (Tykerb) are more effective than individual single agents; long-term adjuvant data are needed.
• Higher rates of pathologic complete responses are observed when pertuzumab/trastuzumab or lapatinib/trastuzumab are added to chemotherapy. Since pathologic complete responses appear to predict long-term outcomes, neoadjuvant studies might inform adjuvant trials.
• Studies should evaluate estrogen receptor (ER)-targeted therapy as integrated into HER2-targeted regimens, perhaps even with a chemotherapy component.
• Targeting of HER1 is probably important. This is not accomplished by pertuzumab/trastuzumab therapy but may be possible with more potent duel or pan HER inhibitors.
• Some HER2-positive patients may be sufficiently treated with targeted therapy alone; their identification should be a research priority.
• Downstream inhibitors combined with receptor inhibitors warrant study in particular subsets, such as patients with PTEN loss or PI3K mutations.

Disclosure: Dr. Osborne has served on advisory boards for AstraZeneca, Novartis, GlaxoSmithKline, Boehringer Ingelheim, Genentech, and Pfizer.