Virginia Kaklamani, MD

Harold Burstein, MD, PhD, FASCO

Press briefing moderator Virginia Kaklamani, MD, Professor of Medicine at The University of Texas Health Science Center, San Antonio, along with Harold Burstein, MD, PhD, FASCO, Associate Professor of Medicine at Harvard Medical School, commented on the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-47 trial for The ASCO Post.

“B-47 is a very important study. There had been subset analyses that raised the intriguing possibility that HER2 1+ or 2+ breast cancers might benefit from trastuzumab (Herceptin). This was an important question to ask and to answer,” Dr. Burstein said. 

“I thought the study was beautifully conducted and unbelievably clean, and it answers the question definitively,” according to Dr. Burstein. “There is no role for trastuzumab in HER2-negative breast cancer.”

While some clinicians have said the definition of HER2 positivity and negativity is unclear to them, he countered, “We are not confused by what HER2 is. A HER2-positive tumor has an immunohistochemistry (IHC) result of 3+ or a fluorescence in situ hybridization (FISH) ratio ≥ 2.0,” he said. “Everything else is either negative or equivocal, such as tumors having a gene copy number greater than six. There are currently zero data that such tumors benefit from trastuzumab.… If a tumor is negative by good IHC and FISH testing, you are done!” 

Role of Tumor Heterogeneity

Dr. Kaklamani believes tumor heterogeneity may explain why previous studies offered a hint of benefit, but the same was not repeated in NSABP B-47. “We see this more and more, now that we are doing neoadjuvant therapy with anti-HER2 agents. Sometimes what remains after we treat is, for example, triple-negative breast cancer. Or we give standard chemotherapy [for HER2-negative disease], then we test, and the tumor is now HER2-positive. We could be killing the part of the tumor that is HER2-negative, but the remaining part may be HER2-positive, which we didn’t know existed,” she said. Retesting can be done, but it is often not reimbursed, she added. 

Despite these nuances, Dr. Kaklamani stated that clinicians should simply “stick to the guidelines” and use anti-HER2 therapy only for patients deemed HER2-positive by appropriate testing. ■

DISCLOSURE: Dr. Kaklamani is a consultant and speaker for Genentech. Dr. Burstein reported no conflicts of interest.