“HER2 is a gene that codes for a protein sitting on the cell surface and sending signals for the cell to grow and divide,” explains Dr. Daniel Haber, Director at Massachusetts General Hospital Cancer Center and Professor of Oncology at Harvard Medical School, about one of the biggest genetic discoveries in breast cancer treatment in recent years.
“It has normal functions, but some cancers make use of HER2 to give themselves extra growth signals,” he continues. “In particular, there is a subset of breast cancer, around 10 percent, that have multiple copies of the gene; instead of the normal two gene copies, one inherited from the mother and one from the father, these cancers can amplify the gene and have 10 or 20 extra copies of the gene, making 10 to 20 more of the protein. In these breast cancers, HER2 signals help ‘drive’ the cancer.”
HER2 is the focus of a recently completed study conducted by a team of 22 investigators including Haber. Entitled “Blood-based monitoring identifies acquired and targetable driver HER2 mutations in endocrine-resistant metastatic breast cancer” and published in the prestigious Precision Oncology journal. The study was partially funded by the National Foundation for Cancer Research, and Haber himself has been funded by NFCR since 2004. While huge strides are made in cancer research and treatment every day, even the baby steps can swallow budgets whole, making organizations such as the NFCR a vital part of how researchers continue their work.
“NFCR has supported my lab for many years, with discretionary funds that I’ve been able to direct to areas of need and urgent priorities,” says Haber. “That kind of flexible funding is rare these days, and it’s made a big difference in my ability to take on high risk projects and follow new avenues that are exciting but not traditional. I’m profoundly grateful for their ongoing and longstanding support over much of my scientific career.”
As the title suggests, Haber’s (et al) study focuses on blood-based monitoring, which is emerging as a robust tool to quantify tumor burden, assess response in patients with solid tumor malignancies as they decrease or increase in response to therapy. Additionally, the process can evaluate the evolution of tumor cell subpopulations. The subject of intense study since 1987, HER2 breast cancer and its treatment have advanced significantly, thanks largely to endocrine-based therapies. Breast cancer, however, is nothing if not tenacious; endocrine resistance often develops. Tumor sampling to identify and monitor the presence of actionable drug resistance-associated mutations is a central tenet of targeted precision oncology.
“Cancers can change over time,” sums Haber. “In particular with breast cancer, where women with advanced disease can receive multiple courses of therapy, cancers can respond to a treatment, then acquire a new mutation that makes them resistant to that treatment, but conceivably could make them sensitive to another treatment.”
Haber’s involvement with cancer goes far beyond this study; he notes he has always been fascinated by the science of cancer research, as well as being profoundly moved by the care of patients facing such a life-threatening illness. Considered one of the wunderkinds of oncology, he has witnessed or taken a direct role in the explosion of novel therapies and successful scientifically-based treatments over the past 10 years.
“I want to have an impact,” says Haber. “To devote myself as much as I can to try to discover new facts about the biology around us and then translate that knowledge into making a difference in the clinic. It’s a challenging goal for all of us in cancer research, and it’s rare to achieve it, but it makes it all worthwhile.”
Haber, et al. (2019). Blood-based monitoring identifies acquired and targetable
driver HER2 mutations in endocrine-resistant metastatic
breast cancer. Retrieved from: https://www.nature.com/articles/s41698-019-0090-5
Mitri, Zahi. (2012). The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New Advances in Therapy. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539433/
Perry, David. (2019). E-mail interview with Dr. Daniel Haber