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HER-2/neu - Molecular Structure and Status. Antibody - Targeted Therapy with Pertuzumab, Trastuzumab and Docetaxel and the Impact on Overall Survival (OS) and Progression-Free Survival (PFS) in Patients with Metastatic Breast Cancer

Dimitar Trizlov, Iliyaz Hadzhiev, Aleksandar Yordanov, Valeriy Yordanov

Abstract

Introduction: HER-2 positive breast cancer is one of the most aggressive and rapidly growing neoplasms, due to the amplification and overexpression of the HER-2/neu gene. The exceeding presence of the receptor on the cell’s membrane makes it a valuable treatment target.

Materials and Methods:  HER-2 receptors are among the main factors controlling the cellular growth, division and self-repair. In approximately 25% of breast cancers, the HER-2 gene mutates, producing too many copies of itself. Several methods are possible for discovering the HER-2 status: immunohistochemistry (IHC) and in situ hybridization (ISH, FISH, CISH, Dual-ISH tests). Positive results on these tests qualify patients for specific antibody-targeted therapy with trastuzumab and pertuzumab. The therapy includes docetaxel combined with trastuzumab or with both trastuzumab and pertuzumab. Scientific studies analyze key aspects such as OS and PFS by conducting double-blind studies comparing pertuzumab+trastuzumab+docetaxel with placebo+trastuzumab+docetaxel. Poll among oncologists was also used to review the efficacy of both treatments.

Results: The result of the study, used as reference, showed that the PFS was prolonged by 6.1 months - from 12.4 in the control group to 18.5 in the group, using pertuzumab, instead of placebo. The OS rates improved from 40.8 to 56.6 months – a 15.8 months increase. Distinct side effect of the treatment - left ventricular dysfunction also drops by 3.9% in the pertuzumab group (from 8.3% to 4.4%). Data, gathered from the study, is further validated by the oncologists polled. The results can be explained by delving into the action mechanism of pertuzumab, which blocks heterodimerization of the HER-2 receptor with other members of the ErbB family, thus complementing the effects of trastuzumab.

Conclusion: The pertuzumab+trastuzumab+docetaxel treatment shows significantly better results in OS and PFS, as opposed to placebo+trastuzumab+docetaxel, when used as first line of therapy, simultaneously lowering cardiovascular side effects.


Keywords

HER-2/neu, overall survival, progression-free survival, antibody-targeted therapy, pertuzumab, trastuzumab


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