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Women with a particularly aggressive form of breast cancer, known as HER2-positive disease, now have unique options that can help tailor their treatment more effectively. Based on results from a phase III clinical trial that followed women for seven years and was conducted at the UNC Lineberger Comprehensive Cancer Center and other cancer centers nationwide, a new therapeutic roadmap may help clinicians figure out which tumors can be treated less aggressively. The findings were published in the Journal of Clinical Oncology.

Human epidermal growth factor receptor 2 (HER2) positivity is found in 15% to 20% of breast cancers. The American Cancer Society predicts nearly 280,000 people in the U.S. will be diagnosed with breast cancer this year. Herceptin (trastuzumab), the first anti-HER2 targeted therapy, was approved by the Food and Drug Administration in 1998 and greatly improved chances of survival in women with HER2-positive disease. However, there are multiple molecular subtypes of HER2-positive breast cancer, each of which responds to treatment differently.

UNC Lineberger’s Lisa Carey, MD, FASCO, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research.

“There is substantial variability in this type of breast cancer from the standpoint of responsiveness to drugs and risk of relapse, so our research helps shine a light on that variability,” said Lisa A. Carey, MD, FASCO, deputy director of clinical science and the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research at UNC Lineberger. “In the future, we will not treat every woman in the same manner. This is what precision medicine is about — the right drugs for the right patient, with the corollary of not giving unnecessary drugs to those who don’t need them.”

The CALGB 40601 trial enrolled 305 women with newly diagnosed HER2-positive disease and randomly assigned them to weekly chemotherapy of paclitaxel with either of two targeted therapies, Herceptin or Tykerb (lapatinib), or a combination of both. After seven years, women on the combination therapy had a nearly two-thirds lower risk of death compared to women who received just one of the targeted therapies.

The analysis also looked at the amount of cancer remaining in a pathology sample after treatment and the chances of surviving with or without the disease relapsing. The researchers found that women with no cancer left after treatment had a very low risk of cancer recurrence. For women with residual cancer, the risk of recurrence was strongly influenced by the molecular subtype of the tumor. Additionally, the investigators found that evidence of an active immune response to the tumor corresponded with both greater likelihood of having tumors eradicated in the breast as well as less likelihood of relapse.

Aranzazu Fernandez-Martinez, MD.

“Based on results from this trial, in the near future we may be able to look at a combination of genetics and immune cell activation to determine how to best individualize treatment,” concluded Aranzazu Fernandez-Martinez, MD, a medical oncologist at UNC Lineberger and first author of the study.

Authors and Disclosures

The trial was run by the Alliance for Clinical Trials in Oncology, which is part of the National Clinical Trials Network sponsored by the National Cancer Institute.

In addition to Carey and Fernandez-Martinez, other authors included Charles M. Perou PhD, Joel S. Parker PhD, Katherine A. Hoadley PhD, and Jonathan Shepherd PhD, UNC Lineberger; Ian E. Krop, MD, PhD, Sara Tolaney, MD, MPH, Eric Winer, MD; and Ann Partridge, MD, MPH, Dana-Farber Cancer Institute; David W. Hillman, MS, Mei-Yin Polley, PhD, and Lucas Huebner, MS, Mayo Clinic, Rochester; N. Lynn Henry, MD, PhD, University of Michigan; Chau Dang, MD, and Clifford Hudis, MD, Memorial Sloan Kettering Cancer Center; Lyndsay Harris, MD, National Cancer Institute; Donald Berry, PhD, MD Anderson Cancer Center; and Olwen Hahn, MD, University of Chicago.

No personal financial interests with any commercial entity.