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

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 2009

• 255/1250 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 populationN (%) Median (range)

Age at diagnosis (years) 45 (26-75)

Triple negative status at primaryYesNoUnknown

17 (9.5)161 (81.5)

77

ER/PgR status at primaryBoth absentER absent, PgR >0ER> 0, PgR absentER>0 and PgR >0

52 (20.4)6 (2.3)

39 (15.3)158 (62.0)

HER2 status at primaryNot overexpressed OverexpressedUnknown

124 (69.6) 54 (30.4)

77

203 cases (79.6%) endocrine responsive tumor expressing ER and/or PgR

Characteristics of patient study populationN (%) Median (range)

Type of treatment received prior to liver biopsy*No treatmentOnly CTOnly HTOnly ITCT+HTCT+ITHT+ITCT+HT+ITUnknown

7 (3.0)54 (23.3)99 (42.7)

2 (0.9)59 (25.4)

3 (1.3)4 (1.7)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 biopsy12≥3

152 (60.6)60 (23.9)39 (15.5)

* 16 pts had liver synchronous mts and were not considered

ResultsQualitative changes in ER status

Overall discordance rate (95% CI): 14.5% (10.4-19.4)

ER Primary TumorNegative 58Positive 197Total 255

turned into

ER Liver MetastasesPositive 15 (25.9%)Negative 22 (11.2%)Total 37 (14.5%)

p=0.001

ResultsQualitative changes in PgR status

Overall discordance rate (95% CI): 48.6% (42.3-54.9)

PgR Primary TumorNegative 91Positive 164Total 255

turned into

PgR Liver MetastasesPositive 18 (19.8%)Negative 106 (64.6%)Total 124 (48.6%)

p<0.0001

ResultsQualitative changes in Her-2/neu status*

HER2 Primary Tumor

turned into

HER2 Liver Metastases

Negative 118 Positive 7 (5.9%)Positive 54 Negative 17 (31.5%)Total 172 * Total 24 (13.9%)

Overall discordance rate (95% CI): 13.9% (9.1-20.1) * 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