The expanding role of pertuzumab in the treatment of HER2-positive breast cancer

I Moya-Horno,1 J Cortés1,2 1Department of Medical Oncology, Instituto Oncológico Baselga, Hospital Quirón, 2Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Barcelona, Spain Abstract: Breast cancer tumors that demonstrate gene amplification or overexpression of human epidermal growth factor receptor 2 (HER2) are classified as HER2-positive. They account for approximately 15% of all breast cancers and represent an adverse prognostic factor. Over the past years, many new therapies have become available for the treatment of breast cancer. Particularly, the treatment of patients with HER2-positive breast cancer has developed with the arrival of anti-HER2 targeted therapies that have been proven to increase survival in both the metastatic and early-stage settings of the disease. Trastuzumab, a monoclonal antibody targeting HER2, significantly improves survival in HER2-positive breast cancer. Nevertheless, it is still a challenge to evolve anti-HER2 therapies, as the disease may progress. Pertuzumab inhibits HER2 by binding to a different HER2 epitope than trastuzumab and represents a complementary mechanism of action to trastuzumab. The efficacy and safety of pertuzumab in combination with trastuzumab with or without chemotherapy have been demonstrated in both advanced and early stages of HER2-positive breast cancer. Herein, we review the available data on the use of pertuzumab for the treatment of patients with HER2-positive breast cancer. Keywords: pertuzumab, anti-HER2 targeted therapies, HER2-positive breast cancer&nbsp

Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients. Cell-free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA-Q-PCR or next-generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty-three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatment decisions, such as initiation of osimertinib treatment or selection of specific ALK tyrosine-kinase inhibitors. In conclusion, fluids close to metastatic sites are superior to blood for the detection of relevant mutations and can offer valuable clinical information, particularly in patients progressing to targeted therapies