Breast cancer is the most common tumour diagnosed in women worldwide and is the second leading cause of cancer death. The use of trastuzumab or Herceptin®, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2) together with chemotherapy has changed the natural history of breast cancers overexpressing HER2. There is mounting evidence that responses differ according to hormone receptor (HR) status. The behaviour of so called “double positive” tumours and how they respond to existing therapies are relevant clinical questions. Late recurrences and risk of death is characteristic of this subtype. HER2 is overexpressed in 25% of all breast cancers. In nearly 50% of these there is co-existence of oestrogen receptor (ER) and progesterone (PgR) expression. Neoadjuvant treatment combining chemotherapy and trastuzumab is standard of care. Pathological complete response (pCR) rates are consistently inferior in HER2 positive patients who are ER positive compared to those with ER negative disease. This review addresses the role for adding endocrine deprivation therapy (EDT) in the neoadjuvant setting.
A computer-based literature search was conducted using the Cochrane library, PubMed and Embase. Results reported at international meetings and ClinicalTrials.gov were also included. Publications were restricted to studies investigating the addition of EDT in the neoadjuvant setting with pCR reported as an outcome of interest.
This systematic review included eight studies. pCR rates were reported on 1,232 women with HER2 positive breast cancer with or without co-existence of ER. The treatment paradigm was wide ranging across the studies with dual anti-Her2 therapy being adopted in favour of chemotherapy free regimens or chemotherapy combined with either single or dual anti-HER2 therapy. pCR rates ranged from 8% to 46.1% in this subtype when EDT was added. The addition of EDT to trastuzumab and chemotherapy in the neoadjuvant setting likely represents a worthwhile, safe and cost-effective approach.
The evidence is compelling to warrant further clinical trials to better identify distinctive subtypes and optimise targeted therapy for HER2 and HR positive breast cancer.
Martina A Smith.
Has not received any funding.
All authors have declared no conflicts of interest.