Change in Receptor Status in Locally Advanced Breast Cancer Patients after Treatment with Neoadjuvant Therapy (NAT).
Authors: Simmons C. , Mashhour M. , Nofech Mozes S. , Hanna W. , Lam A. , Lemon S. , Kiss A. , Mateen M. , Wright F. , Clemons M. , Fitzgerald B. , Dent R. 
Published: December 2010

Background: Systemic treatment decisions for locally advanced breast cancer (LABC) are made upfront, prior to surgery. ER, PR and Her2 status is often assessed on the initial core biopsy, and used to guide systemic therapy options. Hormone receptor and Her2 status may or may not be repeated after definitive surgery. Studies completed in the metastatic setting indicate that hormone receptor status may change between primary and metastatic lesion in up to 40% of cases after adjuvant treatment1. There is limited data with regards to any change occurring in the neoadjuvant setting. This study aimed to determine if a change in receptor status occurs after NAT by reassessing the ER, PR and Her2 status of locally advanced breast cancer specimens after definitive surgery, and to quantify any change observed.Methods: Patients with LABC (stage 2B or stage 3) who were entered into the prospective LABC database at the Sunnybrook Odette Cancer Centre between January 2002 and January 2008 were included. ER and PR status by IHC and Her2 status by IHC and FISH was evaluated in both the pre-treatment core biopsy specimen and in the post-treatment mastectomy specimen using the same technique. ER and PR status was also quantified and reported as percentage postivity.Results: One hundred and fifty (150) patients were enrolled in the LABC database between January 2002 and January 2008. Of these, 9 had mastectomy at a different centre, 15 had a pathological complete response, 13 did not undergo surgery for various reasons post NAT (refusal, progression, comorbidities), and 7 had missing data. The remaining 106 patients had ER and PR status reassessed post mastectomy, and 93 had Her2 status available from both pre and post-treatment specimens. Only 6 patients had a change in ER status, (5.6%, P = NS), but 25 had a change in PR status (23.6%, p = 0.0007). The majority of cases involved a loss in hormone receptor status, with only 4 patients experiencing a gain in PR status. Seven patients had a change in Her2 status (7.5%, P=NS). There was significant discordance in the quantitative analysis of PR but not ER status between specimens pre- and post-treatment, (p = 0.84 for ER, p &lt; 0.0001 for PR). There was no correlation with change in ER or PR and response to NAT.Conclusions: This study has demonstrated a significant discordance of 24% in hormone receptor status between core biopsy and final definitive surgery, primarily as a loss of PR status. Further follow up of these cases may help to determine if loss of PR or significant change in quantization confers predictive or prognostic information.Change in ER status Biopsy ER-Biopsy ER+Mastectomy ER-392Mastectomy ER+461 Change in PR status Biopsy PR-Biopsy PR+Mastectomy PR-514Mastectomy PR+2129 1. Simmons C, Miller N, Geddie W, Gianfelice D, Oldfield M, Dranitsaris G, Clemons M. “Changes in breast tumour receptor status with time – does performing a confirmatory tissue biopsy at the time of metastatic recurrence alter patient management? The results of a prospective study.” Annals of Oncology, March 18, 2009.Change in Her2 status Biopsy Her2-Biopsy Her2+Mastectomy Her2-683Mastectomy Her2+418 

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1083.