Factors influencing diagnosis and outcome in HER2 receptor positive breast cancer

Introduction About 30% of breast cancers are HER2 receptor positive, these breast cancers traditionally had a poor prognosis but the introduction of targeted anti-HER2 therapy (Trastuzumab) has resulted in a vast improvement in survival. However, not all HER2 positive breast cancers patients respond to Trastuzumab and currently there are no markers to predict which patients will respond. Aim To identify new factors which may predict which patients with HER2 positive breast cancer will respond to Trastuzumab therapy. Methods Clinically, a retrospective analysis of all HER2 receptor positive breast cancers in University hospital Galway was performed, along with a systematic review of the literature. An in vitro analysis of potential biomarkers called microRNA was also performed to identify new markers. Finally a multicentre prospective, blinded clinical trial was run to assess if a panel of microRNA could identify which patients would respond to neoadjuvant chemotherapy. Results A patients hormone receptor status was found to be a major factor in disease free survival (DFS) and overall survival (OS) after the introduction of Trastuzumab. The Luminal B HER2 (hormone positive) breast cancers had a greater improvement in DFS and OS after Trastuzumab introduction when compared to HER2+(non-luminal) (hormone negative) breast cancer patients. From a systematic review of the literature it was also found there was a significant variation in loco regional recurrence in the Trastuzumab era, with a lower rates seen in the Luminal B HER2 breast cancer patients when compared to patients with HER2+(non-luminal) breast cancer. From our prospective clinical trial, two microRNA, miR-21 and miR-195 where found to have significant variation in expression between responder and non-responders to chemotherapy. Conclusions In patients with HER2 receptor positive breast cancers, hormone receptor status was found to be a major factor in influencing survival and recurrence rates. We have also identified two potential biomarkers that could be used to predict which patients will respond to neoadjuvant chemotherapy.