Pathological and clinical outcomes following neoadjuvant dual HER2 therapy for early-stage breast cancer: An Australian institutional real-world experience.

AIM: There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non-metastatic HER2-positive breast cancer, which may be used in combination with conventional chemotherapy to optimise pathological responses at surgery. However, these therapies, particularly the chemotherapeutic components, may portend significant and long-lasting toxicity. Hence, de-escalation of treatment intensity has been an area of interest and was evaluated in the phase II NeoSphere study. Herein, we report the real-world pathological and survival outcomes from neoadjuvant taxane and dual HER2 blockade recorded at our centre. METHODS: This was a retrospective cohort study of patients receiving neoadjuvant pertuzumab, trastuzumab and taxane chemotherapy for non-metastatic HER2-positive breast cancer at a single centre in Sydney, Australia. We collected data pertaining to baseline demographic characteristics, pathological response rates, post-surgical prescribing patterns and also undertook survival analyses for invasive disease-free survival (iDFS) as well as exploratory analyses for correlations between pre-specified clinicopathologic factors and pathological response at surgery. RESULTS: Our population was largely similar at baseline to the NeoSphere study. 71 patients were included in the final analysis. 61% achieved a pathological complete response (pCR). Three patients received conventional chemotherapy in the adjuvant setting. 92% of included patients were alive and disease-free at 3 years of follow-up. Only 3 events of recurrence or death were recorded at a median follow-up of 32 months. No significant difference in iDFS was noted between patients achieving pCR and those with residual disease at surgery. CONCLUSION: This study demonstrates that de-escalated adjuvant treatment for HER2-positive early breast cancer achieved favourable pathological and long-term outcomes comparable to large trials, some utilising more intensive chemotherapeutic components.

Pathological outcomes of HER2-positive non-metastatic breast cancer patients treated with neoadjuvant dual anti-HER2 therapy and taxane: An Australian experience.

AIMS: Internationally, there has recently been growing interest in the use of neoadjuvant pertuzumab and trastuzumab in patients with non-metastatic HER-2 positive breast cancer following the NEOSPHERE trial in 2012. However, pertuzumab is currently not funded by the Pharmaceutical Benefits Scheme (PBS) in Australia for use in this setting. The authors sought to assess the clinical and pathological response rates at the time of surgery in patients who received neoadjuvant dual anti-HER2 and taxane therapy in a multidisciplinary breast cancer unit. METHODS: A retrospective case series of all patients treated with the neoadjuvant therapy, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. RESULTS: Nineteen patients were included in the study. Sixty-eight percent of all patients achieved pCR, of which 54% further demonstrated no residual ductal carcinoma in situ. Eight patients (42%) had N1 disease pretreatment, of these 88% demonstrated total pCR in the axilla and the breast. Most adverse effects to treatment were manageable grade 1-2 side effects. CONCLUSION: This is the first reported Australian experience using neoadjuvant dual anti-HER2 and taxane therapy for HER-2 positive nonmetastatic breast cancer. The authors have demonstrated favorable pCR rates for invasive disease compared to the NEOSPHERE trial (68% vs 46%), with reasonable patient tolerability. Larger collaborative data sets are required to fully evaluate correlation of pCR with survival outcomes, and cost-effectiveness. National funding models need to be considered.