Biomarker Defines Subgroup of HER2-positive Breast Cancers Resistant to Herceptin Interview with:
Sherene Loi, MBBS(Hons), FRACP, PhD
Associate Professor, University of Melbourne
Consultant Medical Oncologist, Breast Unit
Head, Translatonal Breast Cancer Genomics and Therapeutics Lab
Cancer Council Victoria John Colebatch Fellow
Peter MacCallum Cancer Centre, East Melbourne
Victoria, Australia What is the background for this study? What are the main findings?

Dr. Loi: Even though HER2 amplification/overexpression is such a strong oncogenic driver in breast cancer, clinical and biological heterogeneity is still evident. Our study was performed to investigate the hypothesis that a subgroup of patients with ER-positive, HER2-positive primary breast cancers seem to have lower responses to anti-HER2 therapy, in this case trastuzumab (trade name Herceptin), and we could better identify this group using both ER and HER2 levels. Our study was designed to try to better define this group so we could potentially evaluate the efficacy of future treatment strategies in this group, particularly as combination anti-HER2 therapy (i.e. trastuzumab and pertuzumab) is currently being investigated in the adjuvant setting. What should clinicians and patients take away from your report?

Dr. Loi: We found that a subgroup of these ER-positive (by IHC) patients with the highest expression of ESR1 messenger RNA and/or have low amplified HER2 levels calculated using FISH ratios (<5), do seem to be less dependent on oncogenic HER2 signaling and hence derived less benefit from trastuzumab in the HERA study. We wonder if these patients may benefit more from escalation of endocrine directed therapy rather than HER2 directed therapy. What recommendations do you have for future research as a result of this study?

Dr. Loi: We hope that the principal investigators of the other large adjuvant trastuzumab trials could also investigate the magnitude of benefit of trastuzumab in this group in their phase III studies. If further validated, future studies in HER2 therapy should look at ER-positive subgroup and treatment response in closer detail and future treatment strategies in HER2-positive disease may need to be based and powered according to ER status.


Schott AF. Adjuvant Trastuzumab Benefit in Patients Diagnosed With Triple-Positive Breast Cancer . JAMA Oncol. Published online April 21, 2016. doi:10.1001/jamaoncol.2016.0446.

[wysija_form id=”5″]



Last Updated on April 25, 2016 by Marie Benz MD FAAD