Better Targeting for Targeted Therapy

June 2010, Vol 1, No 2 - IMPAKT Breast Cancer Conference

Brussels—Researchers attempting to understand why some women with human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to drugs designed to target this molecule have found that inhibiting the PI3K/AKT molecular pathway instead may offer greater therapeutic benefit for this group. The findings were presented at the IMPAKT [Improving Care and Knowledge Through Translational Research] Breast Cancer Conference, held May 5-8.

The overexpression of HER2 is an important marker in breast cancer, and it has been associated with a poor outcome for women. The advent of anti-HER2 targeted agents has improved the prognosis for these women. Even so, oncologists have known for some time that some HER2+ breast cancers do not respond to trastuzumab (Herceptin, Genentech), currently the most commonly prescribed anti-HER2 agent.

Sherene Loi, MD, PhDA United States/Belgian research team, led by Sherene Loi, MD, PhD, from the Institute Jules Bordet in Brussels, examined whether and how estrogen receptor (ER) status was involved in the biology of HER2+ breast cancer and response to anti-HER2 therapies.

In a press release describing the study, Dr Loi detailed the approach, saying, “We looked at HER2+ breast cancer using gene expression data, array comparative genomic hybridization, cell lines, and clinical data from nearly 2000 patients.” What they found was that the “estrogen receptor status of HER2+ breast cancer seems to be correlated with different responses to anti-HER therapies. Currently, the biological differences in the group of breast cancers that overexpress HER2 are largely unknown.”

The PI3K/AKT molecular pathway may be the dominant biological pathway for tumor growth and progression, say the authors, and so patients with ER+/HER2+ breast cancers (rather than ER-/HER2+ variety) may be better treated with drugs impacting this pathway.

“Our data suggest that inhibition of estrogen receptor—alone and in combination with such an inhibitor—could actually result in a worse outcome for the patient,” Dr Loi added.