Poor survival outcomes in HER2 positive breast cancer patients with low grade, node negative tumours. Implications for trastuzumab therapy?.
Authors: SM Tovey, S Marla, S Brown, P Burton, P Canney, S Stallard, E Mallon, J Edwards, T Cooke
Journal: Cancer Research (2009)

Abstract Abstract #702 HER2 status is established as a poor prognostic marker for survival in breast cancer and has been validated as a predictive marker for response to trastuzumab following chemotherapy.We determined the number of patients both eligible for and actually receiving trastuzumab therapy for early breast cancer (EBC) in 2006 in a tertiary breast oncology unit. We also performed a retrospective analysis of the impact of HER2 status on survival in a large cohort of low grade, node negative patients who would currently be deemed ineligible for trastuzumab treatment.&amp;#x2028; Methods&amp;#x2028; 1. Data for all patients diagnosed with EBC in 2006 was recorded prospectively in a database. Case notes were consulted where the HER2positive patients had not received trastuzumab, to ascertain the reasons.&amp;#x2028; 2. A retrospective cohort of 367, grade 1 or 2, node negative patients diagnosed between 1980-2002 (median followup 6.2yrs) was analysed to assess the impact of HER2 status (Herceptest 3+/FISHpos) on survival.&amp;#x2028; Results&amp;#x2028; 1. A total of 951 patients were diagnosed with Breast Cancer in 2006. 417(43.9%) of these were screen-detected. 123(12.9%) were HER2positive (117 were EBC) and 59 (50.4%) of the HER2 positive EBCs received trastuzumab therapy. Of the 58 (49.6%) patients who did not receive trastuzumab, 25 (43%) were patients considered low risk due to small, node negative, low grade tumours.&amp;#x2028; 2. Retrospective cohort. The overall hazard ratio for HER2 positivity was 6.78 with 5yr breast cancer specific survival rates of 96% (HER2 neg) and 68% (HER2 pos). The reduction in survival in HER2 positive cases persisted when patients were split into subgroups by ER status, tumour size and age.&amp;#x2028; &amp;#x2028; Conclusions&amp;#x2028; Only 50% of our HER2 positive EBC patients received trastuzumab therapy in 2006. The commonest reason for not receiving trastuzumab was low risk status precluding chemotherapy.&amp;#x2028; However, the substantial reduction in survival shown in our retrospective cohort provides support for the use of trastuzumab in these 'low risk' HER2 positive patients who typically are classified as very good prognosis, are not routinely offered standard chemotherapy, and as such do not fit current prescribing guidelines for trastuzumab. A clinical trial to assess the benefit of adjuvant trastuzumab alone in this group of patients is suggested. Our results are in keeping with the HERA trial where the best prognosis tumours (node negative and size 1-2cm) had benefit similar to the overall cohort.&amp;#x2028; The persistence of poor outcomes in our ER positive subgroup despite endocrine therapy confirms the recent trans-ATAC analysis based on HER2 status and suggests that we cannot not rely solely on adjuvant endocrine therapy in these largely ER positive patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 702.