HER2-positive breast cancer represents about 25 percent of all breast cancers. Once a deadly disease with few treatment options, early stage HER2-positive breast cancer is now a treatable disease with a good prognosis for many patients.
The reason for this lies in what we call targeted therapy. Because the HER2 protein is what makes these tumors particularly aggressive, it is also an effective target in treating the disease.
BCRF researcher Dr. Kent Osborne spoke with BCRF at the 2018 AACR Annual Meeting and discussed the development of HER2-targeted therapies and what’s next for HER2-positive breast cancer. At the meeting, he gave a talk on the subject as the AACR 2018 recipient of the Distinguished Award for Extraordinary Scientific Achievement and Leadership in Breast Cancer Research.
When tumor cells become addicted, they make easy targets
HER2 is a protein that is usually not present on adult cells. Its normal role is in promoting growth during development. When it is present on cancer cells, its powerful growth promoting properties fuel cancer cell growth; so much so that cancer cells can become addicted–in other words depend on it for growth. Dr. Osborne calls this “oncogene addiction” and explained, “If you can shut that down, you should have a pretty good anti-cancer therapy.”
This oncogene addiction led to the development of anti-HER2 therapies like trastuzumab (Herceptin®). Today there are multiple treatment options for women with HER2 breast cancer including combinations of chemotherapy and multiple targeted therapies.
Like the child’s game “whack a mole” when one target is eliminated another pops up.
Resistance to HER2-directed treatments remains a serious clinical concern. Dr. Osborne explained that scientists are just beginning to understand why some HER2 tumors are resistant or become resistant to HER2-targeted therapies.
One way tumors become resistant is by reprogramming other pathways when the HER2 protein is shut down. This may include increasing activity of the estrogen receptor or altering the expression levels of genes such as PIK3CA and PTEN, well established growth promoting and tumor suppressing genes, respectively.
When less is more
For some patients, de-escalation of therapy is more appropriate, meaning that they will do just as well with less treatment with the advantage of not being exposed to side effects of drugs that don’t add benefit. However, determining who these patients are remains a challenge for researchers and physicians alike.
Using patient samples from clinical trials, Dr. Osborne’s team found that patients whose tumors had mutations PIK3CA or PTEN were resistant to HER2 therapy. In other cases, the amount of HER2 protein may help to identify patients who may need more aggressive therapy or will do well with HER2 therapy alone.
What is the future for HER2 positive breast cancer?
Advances are being made today that will continue to personalize therapy for this type of breast cancer. Identifying markers of resistance will help to stratify patients to more, or less treatment. Rational combinations that target multiple tumor pathways or enhance anti-tumor immunity may help many patients whose tumors don’t respond or stop responding to HER2 therapies.
As a clinician, Dr. Osborne has witnessed the progress made in HER2-positive breast cancer treatment firsthand.
“It used to be a bad thing,” he says remembering how the subtype was characterized by its poor prognosis. “But now it’s a good thing because we have very effective treatments.”
You can view the full interview with Dr. Osborne below:
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