Joyce A. O’Shaughnessy, MD
Co-Director, Breast Cancer Research, Baylor Charles A. Sammons Cancer Center, Texas Oncology/US Oncology, Dallas, TX
As the molecular understanding of breast cancer continues to evolve, the search for treatment targets based upon tumor subtypes and gene expression patterns is intensifying.
Joyce A. O’Shaughnessy, MD, who has focused much of her own research on novel therapeutics, has made the translation of emerging concepts to clinical practice a feature of the conferences she organizes through Physicians’ Education Resource (PER). O’Shaughnessy is the program director for the 11th International Congress on The Future of Breast Cancer, scheduled for July 26-28 in Coronado, California, and the 9th Annual School of Breast Oncology, slated for November 1-4 in Atlanta. Georgia.
In this interview, she discusses several broad trends in HER2-positive and triple-negative breast cancers.OncologyLive: What will the addition of new agents to the treatment armamentarium for HER2-positive breast cancer mean for current treatment paradigms?
Pertuzumab will change the standard of care for first-line, metastatic HER2-positive disease. Instead of the standard being a taxane and trastuzumab, pertuzumab will be added as a third agent, and it will further improve the progressionfree survival substantially for patients. Then, it is also being evaluated in adjuvant and neoadjuvant studies. Usually such an active agent in the metastatic setting will translate into benefit in the adjuvant setting as well. Although it will be some years before we have that data, it’s something we’ll be able to anticipate that we’ll be able to bring pertuzumab into the adjuvant setting in the future. But for now, it will change the first-line, metastatic HER2-positive standard.Triple-negative breast cancer has proved particularly challenging with regard to finding a target that responds to drugs. What makes this subtype different?
Two things make it difficult to really nail down targets. One is that there are so many different subtypes of triple negative. The basal and the luminal are the biggest differentiators, but at San Antonio in 2011, I presented an oral presentation on total genome sequencing of 14 metastatic triple-negative breast cancers, and what is so striking about those data is how unique each cancer is.
I think that is because one of the hallmarks of triple-negative breast cancer is genomic instability— problems with DNA repair. There are a number of ways to become a cancer, and with genomic instability, the cancer can go in many different directions in terms of which mutations it’s going to pick up to become a cancer.
There are a number of subtypes within triple-negative breast cancer that we still don’t fully understand, although we’re making progress. But even within those subtypes, within the basal, within the luminal, within the apocrine androgen receptor-positive, there’s going to be differences in driving mutations. This may end up being true personalized medicine in terms of identifying targets that patients will benefit from.
Considering the results with the PARP inhibitors in triple-negative breast cancer, is there still interest in targeting DNA repair pathways?
Snapshot of Breast Cancer Subtypes
Incidence Among 1501 Women
A population-based study of the tumor status of women diagnosed with breast cancer in the Atlanta, Georgia, metropolitan area yielded these incidence rates by broad subtype.
ER indicates estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor; TNBC, triple-negative breast cancer.
Adapted from Lund MJ, Butler EN, Hair BY, et al. Age/race differences in HER2 testing and in incidence rates for breast cancer triple subtypes: a population-based study and first report [published online ahead of print March 24, 2010]. Cancer. 2010; 116(11):2549-2559. doi:10.1002/cncr.25016.
Yes, there really is. The key, however, is to really be able to identify the subset of patients with triple-negative breast cancer where homologous recombination defects are very, very dominant and really provide an Achilles heel of the cancer. The leading hypothesis is that the patients who have the true basal cancers may be the subtype of triple-negatives that have homologous recombination defects.