HER2+ cancer has been known as aggressive 17

From 1984 to 1993, breast carcinoma tissue from 220 primary breast cancer biopsies was obtained from randomly selected patients at Glasgow Royal Infirmary.

  • Tumor tissue from 50 patients was HER2-positive*
  • Overall survival was significantly lower (P<0.0001) in HER2-positive patients vs HER2-negative patients

These patients did not receive HER2-targeted therapy.

HER2+ status is still associated with aggressive breast cancer

*HER2 was localized using the ICR12 antibody and immunohistochemistry (IHC) staining. Survival curves include patients with strongly stained tumors (IHC 3+ was HER2+; n=50) vs weakly stained tumors (IHC 0 or 1+ was HER2–; n=85) tumors. The remaining 85 tumors in the study were considered moderately stained (IHC 2). 17
P-value represents log-rank difference in cumulative survival. 17

Herceptin is recommended as a foundation of therapy for patients, part of the standard of care for HER2+ treatment 1-4

Proposed mechanism of action for Herceptin 1

Herceptin is a monoclonal antibody specifically designed to target HER2 receptors, which are transmembrane receptors on both normal cells and HER2+ tumor cells. 18 HER2 plays an important role in the signaling network that drives cell proliferation. 19

Herceptin is believed to block intracellular signaling pathways. By attenuating the signal transduction downstream, Herceptin may promote apoptosis and arrest cell proliferation. 18

Herceptin also flags the tumor cell for destruction by the body's immune system, known as antibody-dependent cellular cytotoxicity (ADCC). Activation of natural killer cells expressing the Fc gamma receptor, which can be bound by the Fc domain of Herceptin, is mainly what leads to ADCC. 18

In addition, Herceptin prevents HER2 shedding. The potential clinical value is based on observations that high serum levels of HER2 extracellular domain correlate with poor prognosis and decreased responsiveness to endocrine therapy and chemotherapy in patients with advanced breast cancer. 18,19