Poor survival outcomes in HER2-positive breast cancer patients with low-grade, node-negative tumours

Abstract

We present a retrospective analysis on a cohort of low-grade, node-negative patients showing that human epidermal growth factor receptor 2 (HER2) status significantly affects the survival in this otherwise very good prognostic group. Our results provide support for the use of adjuvant trastuzumab in patients who are typically classified as having very good prognosis, not routinely offered standard chemotherapy, and who as such do not fit current UK prescribing guidelines for trastuzumab. Human epidermal growth factor receptor 2 (HER2) amplification has become the prototype biomarker for translation of a laboratory discovery through to development of a highly successful individualised biological therapy agent. Slamon et al (1987) established HER2 as a poor prognostic marker for survival in breast cancer and developed a monoclonal antibody, trastuzumab, targeted to HER2, as a novel therapy for breast cancer patients. More recently, randomised trials in early breast cancer have shown the clinical benefit of trastuzumab after chemotherapy with significant overall survival benefit over chemotherapy alone (Romond et al, 2005;Slamon et al, 2006;Smith et al, 2007). As a result, trastuzumab has been introduced into routine clinical practice in the UK for HER2-positive patients who have completed their standard adjuvant treatment. Current Scottish and National Institute for Health and Clinical Excellence (NICE) guidelines parallel the herceptin adjuvant (HERA) trial entry criteria, according to which trastuzumab is offered only to those patients who have already received standard chemotherapy regimes as part of their treatment regime.However, there remains a small subset of HER2-positive patients who are low grade and node negative and who are currently ineligible for trastuzumab treatment as clinically they have been deemed to have no requirement for standard adjuvant chemotherapy. In our region, approximately 25% of HER2 patients are not offered herceptin as they are deemed to be at 'low risk' (personal communication). Our study analyses a retrospective cohort of lowgrade and node-negative tumours, traditionally classified by Nottingham Prognostic Index (NPI) and Adjuvant! Online as 'low risk' to assess whether HER2 positivity affects survival in this otherwise very good prognostic group. METHODS PatientsWe have a large cohort (n ¼ 1351) of breast cancers diagnosed between 1980 -2002 with full clinical follow-up (median 6.5 years) and pathological details taken from pathology reports. Tissue specimens from these cancers had been used to create tissue microarray technology (TMA) for research purposes (ethical approval was obtained). The grades of tumours from the cohorts diagnosed in the 1980 -90s were reviewed for accuracy by a consultant pathologist (EAM). From this database, we wished to identify a group of patients who would classically be identified as 'low risk'. We selected all node-negative, grade 1 or 2 cancers (n ¼ 362) for further analysis. Human epidermal growth factor receptor 2 status assessmentHuman epider...

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