Abstract P3-14-09: Should testing for estrogen receptor, progesterone receptor and HER2 be repeated following neoadjuvant chemotherapy?
Authors: Shaaban AM , Gahlut R , Fatayer H , Dodwell D , Velikova G , Perren T , Dall BJ , Sharma N , Lansdown M 
Published: August 2014

Introduction

Neoadjuvant chemotherapy (NACT) is increasingly being used for the management of breast carcinomas including inflammatory breast carcinoma and locally advanced cancer. Testing for molecular markers (ER/PR/HER2) is generally performed on the pre-treatment biopsy sample. It is not known whether the histological type, grade and/or molecular profile of those tumour change as a result of chemotherapy. Potential changes particularly from negative to positive status may provide further treatment options for those patients.

Materials & Method

Patients who underwent NACT for primary and operable invasive carcinoma in the period between 2005 to 2009 were identified from the database of a single large UK tertiary referral breast unit. Comprehensive data on chemotherapy regimen, surgical treatment, pathological response and survival were collected. For residual invasive disease (partial pathological response), slides were reviewed and a representative block was selected and marked for tissue microarray (TMA) construction. TMA and pre treatment core biopsy sections, where available, were stained for ER/PR and HER2. Histological type and grade of invasive carcinoma were recorded for pre and post treatment samples for each patient.

Results

A total of 124 patients including 19 presenting as inflammatory carcinoma were included. Median age was 46yrs, IQ range = 41-53. Patients predominantly received anthracyclin-based therapy. Complete pathological response was achieved in 21.8% of patients.

The commonest histological type on core biopsy was ductal carcinoma of no special type (n = 108, 63.9%) followed by lobular (7), mixed (5), metaplastic (2) and mucinous (2). There was a change in histological type in 14.9% of cases. Of the partial responders, grade was available on excision of 111 patients (additional 6 were not gradable). The histological grade was different between the core biopsy and final excision in 29 tumours (26%) including 10 upgrades and 19 downgrades (p&lt;0.001). The downgrade was due to increase in tubule formation and decrease in mitotic count on the final excision sample.

Out of 83 ER stained paired pre and post tumour samples, 7 tumours (8.4%) changed profile from ER negative (Allred score 0/8) to positive (score 2 or above) including a strongly positive tumour (score 7/8) and 2 from positive to negative. Three out of 80 cases changed from PR negative to positive including a moderately positive case (6/8) whereas 2 changed from positive to negative. HER2 status changed from negative to positive in one patient and positive to negative in 2 /72 cases.

Conclusion

Significant changes in histological grade, type and molecular marker status occur following neoadjuvant chemotherapy. Tumours were more likely to be downgraded than upgraded following NACT. Changes in the ER, PR and HER2 status following chemotherapy occurred in 12%, 6.3% and 4.2% of cases respectively. This may have important implications in tailoring treatment options for patients that would otherwise be denied hormonal and/or Herceptin therapy if testing was solely done on the pre-treatment biopsy. Based on this data, we recommend repeat testing on residual carcinoma and prospective collection of data on management and outcome of those patients.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-09.