HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

Abstract

Untreated human epidermal growth factor receptor‐2 (HER‐2)‐positive advanced breast cancer (ABC) is an aggressive disease, associated with a poor prognosis and short overall survival. HER‐2‐directed therapy prolongs both time to disease progression and overall survival when combined with chemotherapy and has become the standard of care for those with HER‐2‐positive breast cancer in the early and advanced settings. Despite the remarkable therapeutic impact HER‐2‐directed therapy has had on disease outcomes, some patients with HER‐2‐positive disease will have primary resistant disease and others will respond initially but will eventually have progression, underscoring the need for other novel therapeutic options. This article reviews recent phase III trial data and discusses a practical approach to sequencing of HER‐2‐directed therapy in patients with HER‐2‐positive ABC. The significant cumulative survival gains seen in these trials are slowly reshaping the landscape of HER‐2‐positive ABC outcomes.

Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions

“…Lack of significance, though, could be due to a type 2 error (false negative) based on less than expected accrual. These studies support the use of HER-2 targeted treatments combined with non-steroidal aromatase inhibitors, in post-menopausal patients, as a valid chemotherapy-free option for triple positive patients [66] .…”

“…The regimen was effective in treating both, CNS and extra-CNS disease, and delayed whole brain radiotherapy by a median of 8 mo [70] . The conclusions from a planned randomized study evaluating capecitabine plus lapatinib plus whole brain radiotherapy are expected soon [66] .…”

SHP-1 reverses trastuzumab resistance and migration in HER2-positive breast cancer cells through the stat3/p-stat3 pathway

“…Trastuzumab (Herceptin) was the first monoclonal antibody to be approved for targeted therapeutic use, either alone or in combination with the chemotherapy drug paclitaxel, in the treatment of metastatic HER-2-positive breast cancer [7]. Although many patients with metastatic HER-2+ breast cancer respond positively in clinical treatments to the first-line agent trastuzumab, virtually all patients eventually adapt to the anti-HER2 therapy and the disease progresses [8][9][10].…”

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System

“…The overall survival was reported to be 56.5 months, which represents an increase of approximately 16 months [16]. In Canada, trastuzumab and pertuzumab in combination with chemotherapy is included as part of the established standard of care for first-line treatment of patients with HER2-positive metastatic breast cancer [17]. However, until recently, therapeutic options for women who have progressed on trastuzumab-based therapy were limited.…”