Should liver metastases of breast cancer be biopsied to improve treatment choice? M. A. Locatelli, G. Curigliano, L. Fumagalli, V. Bagnardi, G. Aurilio, P. Della Vigna, L. Monfardini, S. Giudici, G. Viale, A. Goldhirsch European Institute of Oncology, Milan, Italy Abstract # CRA 1008 Chicago, June 08, 2010

Purpose To evaluate the rate of discordance of estrogen receptor (ER), progesterone receptor (PgR) and HER2 receptor status between primary breast cancer (BC) and liver metastases To evaluate its potential impact on treatment choice

Background Determination of ER, PgR and HER2 status in the primary tumor is clinically relevant to define:  the BC subtypes  the clinical outcome  the choice of therapy

Background Nonetheless, currently the acquisition of tissue from metastatic lesions is not recommended as a routine practice

Patients and Methods Retrospective analysis of 1250 ultrasound guided liver biopsies performed at IEO from August 1999 to March /1250 were identified as consecutive female BC The occurrence of ER, PgR and HER2 discordance in liver metastasis and primitive BC was evaluated

Patients and Methods: Inclusion Criteria Histological diagnosis of primary BC Unilateral BC with development of liver metastasis Recorded expression status of ER, PgR, HER2 in both primary BC and liver metastasis Any form of therapy: surgical, systemic, and radio

Patients and Methods: Exclusion Criteria Bilateral BC Male Gender Ductal carcinoma in situ as initial diagnosis Synchronous metastases

Characteristics of patient study population N (%)Median (range) Age at diagnosis (years)45 (26-75) Triple negative status at primary Yes No Unknown 17 (9.5) 161 (81.5) 77 ER/PgR status at primary Both absent ER absent, PgR >0 ER> 0, PgR absent ER>0 and PgR >0 52 (20.4) 6 (2.3) 39 (15.3) 158 (62.0) HER2 status at primary Not overexpressed Overexpressed Unknown 124 (69.6) 54 (30.4) cases (79.6%) endocrine responsive tumor expressing ER and/or PgR

Characteristics of patient study population N (%)Median (range) Type of treatment received prior to liver biopsy * No treatment Only CT Only HT Only IT CT+HT CT+IT HT+IT CT+HT+IT Unknown 7 (3.0) 54 (23.3) 99 (42.7) 2 (0.9) 59 (25.4) 3 (1.3) 4 (1.7) 7 Time from diagnosis to liver biopsy (years) 3.4 (0-18.3) Number of metastatic sites at the time of liver biopsy 1 2 ≥3 152 (60.6) 60 (23.9) 39 (15.5) * 16 pts had liver synchronous mts and were not considered

Results Qualitative changes in ER status Overall discordance rate (95% CI): 14.5% ( ) ER Primary Tumor Negative58 Positive197 Total255 turned into ER Liver Metastases Positive15 (25.9%) Negative22 (11.2%) Total37 (14.5%) p=0.001

Results Qualitative changes in PgR status Overall discordance rate (95% CI): 48.6% ( ) PgR Primary Tumor Negative91 Positive164 Total255 turned into PgR Liver Metastases Positive18 (19.8%) Negative106 (64.6%) Total124 (48.6%) p<0.0001

Results Qualitative changes in Her-2/neu status* HER2 Primary Tumor turned into HER2 Liver Metastases Negative118Positive7 (5.9%) Positive54Negative17 (31.5%) Total172 *Total24 (13.9%) Overall discordance rate (95% CI): 13.9% ( ) * 83 pts with missing value at primary or at liver biopsy were not considered p<0.001

Impact of the receptor status discordance on therapy choices Overall, discordance in ER/PgR and/or HER2 status between primary and liver metastases

Summary “In the era of continuing biological and therapeutic advances should we continue to use a historical pathological snapshot of the primary tumor or should we reassess biology of metastatic disease?”

Summary In our study discordance for ER, PgR, and HER2 status between primary tumor and liver metastases was 14.5%, 48.6%, and 13.9% respectively, which led to a change of the therapy for 31 out of 255 pts (12.1%) The main limitation is related to the retrospective analysis Another limitation is related to the manual scoring of ER, PgR and HER2

Conclusions There is emerging evidence that tumor receptor status may change dynamically during the natural history of the disease When safe and easy to perform, a biopsy of the metastatic lesion should be considered in all patients, particularly when there is a long interval from the first diagnosis, since it is likely to impact treatment choice.

Acknowledgements : Aron Goldhirsch Giuseppe Curigliano Giuseppe Viale Luca Fumagalli Vincenzo Bagnardi Simona Giudici Gaetano Aurilio Paolo Della Vigna Lorenzo Monfardini … and to all patients