First-line therapy in HER2 positive metastatic breast cancer: is the mosaic fully completed or are we missing additional pieces?

Abstract

The discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for women with early-stage and advanced HER2-positive breast cancer (BC).HER-2 targeted therapies represent a major step forward in achieving the goal of delivering individualized targeted therapy for BC, and trastuzumab was the first anti-HER-2 strategy to be approved for treatment of HER-2 positive BC.This review discusses the treatment of metastatic HER2-positive BC and describes efficacy and safety of novel anti-HER2 target therapies in first-line metastatic settings and the future challenges include refining such treatments, reducing toxicity and simultaneously developing innovative therapies. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.In the next future will be possible to use an ample armamentarium of combination therapies directed against HER2 and key signaling components integrated in the HER network. This approach will allow clinicians to tailor the management of the individual patient on the basis of tumor- specific biomarker profiles.There is an urgent need for prospective biomarker-driven trials to identify patients for whom targeting is cost-effective.

Potential Targets' Analysis Reveals Dual PI3K/mTOR Pathway Inhibition as a Promising Therapeutic Strategy for Uterine Leiomyosarcomas—an ENITEC Group Initiative

“…PDGFR, ERBB2, and EGFR all have proven to be valuable targets in other cancer types. PDGFR, for example, is blocked by imatinib in gastrointestinal stromal tumors and dermatofibrosarcoma protuberans (9), whereas ERBB2 overexpression is tackled by the anti-ERBB2 antibodies trastuzumab and pertuzumab in breast cancer (10). Finally, EGFR is targeted by antibodies such as panitumumab in head and neck and colon cancer, and by tyrosine kinase inhibitors gefitinib and erlotinib in non-small cell lung cancer (11).…”

Herceptin® (trastuzumab) in HER2-positive early breast cancer: protocol for a systematic review and cumulative network meta-analysis

“…The overexpression of HER2, termed HER2-positive (HER2+), can result in uncontrolled growth and division of breast cells [ 3 ]. Approximately 20% of all invasive breast cancers are HER2+, which is a particularly aggressive form of the disease [ 4 , 5 ]. Before current treatment options became available, only 2–5% of HER2+ breast cancer patients were classified as “long-term survivors” [ 4 ].…”

“…Approximately 20% of all invasive breast cancers are HER2+, which is a particularly aggressive form of the disease [ 4 , 5 ]. Before current treatment options became available, only 2–5% of HER2+ breast cancer patients were classified as “long-term survivors” [ 4 ]. Fortunately, HER2-targeted therapies have been developed beginning with originator trastuzumab (Herceptin®; F. Hoffmann-La Roche Ltd.) in the 1990s to help combat this aggressive cancer.…”

The evolving role of receptors as predictive biomarkers for metastatic breast cancer

“…Patients have also been shown to derive benefit from combination of anti-HER2 drugs with endocrine therapy in ER+/HER2+ MBC cases [75,76,78]. Research continues to assess the potential of treatment strategies that combine anti-HER therapies with agents targeting other pathways and signalling components in the HER network, such as CDK4/6, PI3K and mTOR inhibitors [74,75,[103][104][105].…”