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The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer
Authors:Robin L. Jones  Janine Salter  Roger A’Hern  Ash Nerurkar  Marina Parton  Jorge S. Reis-Filho  Ian E. Smith  Mitchell Dowsett
Affiliation:(1) Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK;(2) Institute of Cancer Research Clinical Trials and Statistics Unit, Sutton, Surrey, UK;(3) Breast Unit, Royal Marsden Hospital, London, UK;(4) Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
Abstract:Purpose To compare the prognostic significance of proliferation, as assessed by Ki67 expression, in breast cancer before and after neoadjuvant chemotherapy. Methods A retrospective search of a prospectively maintained clinical database was performed to identify patients treated with neoadjuvant chemotherapy at the Royal Marsden Hospital. The expression of Ki67 was assessed using immunohistochemistry in pre-therapy core-needle biopsy and post-therapy surgical excision specimens. The following factors were considered pre- and post-chemotherapy for their relationship with relapse-free and overall survival: age, menstrual status, T and N stage, pre-therapy operability, Ki67, ER, PgR, HER2, grade, histological subtype, vascular invasion, clinical response, chemotherapy regimen, type of surgery performed, adjuvant therapy, pathological tumour size and nodal involvement. Results In a matched cohort of 103 patients, on multivariate analysis of relapse-free survival, post-therapy Ki67 was the only significant independent prognostic factor. On multivariate analysis for overall survival, both pre- and excision Ki67 were significant independent predictors but the latter showed a stronger prognostic impact. The highest and lowest tertiles of excision Ki67 had different prognosis for both 5-year relapse-free (27% vs. 77%) and overall (39% and 93%) survival. In a cohort of 284 patients with only excision samples, post-therapy Ki67 was a significant independent prognostic factor on multivariate analysis. Conclusion Post-chemotherapy Ki67 is a strong predictor of outcome for patients not achieving a pathological complete response.
Keywords:Breast cancer  Neoadjuvant chemotherapy  Post-therapy proliferation
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