A New Pathological Response Index (PRI) for Neoadjuvant Chemotherapy Accurately Predicts Clinical Outcomes of Locally Advanced Primary Breast Cancers (LAPBC).
Tarek MA Abdel-fatah, Paul M Mosley, Andrew Lee, Sarah Pinder, Jorge S Reis-Filho, Ian O Ellis, Steve Y Chan. School of Molecular Medical Science, Nottingham University City Hospitals, United Kingdom; Kings College London, Guy's and St Thomas'Hospitals, London, United Kingdom; Institute of Cancer Research, London, United Kingdom
Background: Pathological complete response (pCR) after neoadjuvant therapy (NACT) predicts overall survival (OS). However; pCR is not a perfect surrogate for OS, given that a significant number of patients that do not achieve pCR benefit from chemotherapy. Furthermore, residual cancer cells after NACT includes a wide range of responses from near pCR to complete resistance.
Design: In this study we performed a comprehensive pathological assessment for 195 surgical specimens of LAPBC, removed after receiving anthracycline based chemotherapy with or without Taxane with long clinical follow-up (median > 10 years).
Results: A multivariate Cox regression model revealed that large size (>3cm) of the residual tumuor (p=0.001), presence of lympho-vascular invasion (LVI) after NACT (p=0.004), absence of fibrotic reaction at the site of the primary tumour or lymph nodes (LN) after NACT (p<0.001), and presence of ≥4 positive axillary LN including at least one apical LN (p=0.003) at surgery were significantly associated with shorter progression free survival (PFS). These results were used to develop a PRI from which 4 subgroups with distinct clinical outcomes were identified. Patients with PRI-1 (n=92) had a good clinical outcomes in both ER+ (10-year PFS; 91%) and ER- tumours (10-year PFS; 84%). Patients with PRI-1 who did not show pCR (n=54) had equivalent OS and PFS as those with PRI-1 who achieved pCR (n=38); p=NS. Patients with PRI-2, PRI-3 and PRI-4 had a 3-14 fold increase in the risk of progression compared to those with PRI-1. ER+ patients with either PRI-3 or PRI-4 had 5-year PFS rates of 38%-45% despite ongoing treatment with adjuvant therapy.
Conclusions: In conclusion, a PRI including size of residual tumour, LN stage, LVI and any evidence of fibrotic reaction following NACT may accurately predict the disease progression rate, identify a greater proportion of patients who could potentially benefit from the NACT and may be able to spared further adjuvant therapy (near pCR), help to improve the sensitivity of pathological response to predict tumours response/resistance to a given NACT regimen and enable biological markers to be studied in a good prognostic group other than pCR.
Tuesday, March 1, 2011 11:00 AM
Platform Session: Section C, Tuesday Morning