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E. Amir, M. Clemons, O.C. Freedman, N. Miller, R.E. Coleman, C. Purdie, L. Jordan, P. Quinlan, A.M. Thompson Tissue confirmation of disease recurrence.

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Presentation on theme: "E. Amir, M. Clemons, O.C. Freedman, N. Miller, R.E. Coleman, C. Purdie, L. Jordan, P. Quinlan, A.M. Thompson Tissue confirmation of disease recurrence."— Presentation transcript:

1 E. Amir, M. Clemons, O.C. Freedman, N. Miller, R.E. Coleman, C. Purdie, L. Jordan, P. Quinlan, A.M. Thompson Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of two large prospective studies

2 Disclosures Eitan Amir and Orit Freedman declare they have received honoraria from AstraZeneca. Mark Clemons declares honoraria, research funding and advisory board involvement with AstraZeneca, Roche and Novartis pharmaceuticals. Alastair Thompson, Colin Purdie, Phil Quinlan and Lee Jordan declare they have received research funding from AstraZeneca.

3 Treatment of Recurrent Breast Cancer Primary breast cancer ER PgR HER2 Months/years Recurrent breast cancer Progression Months/years Tumor Characteristics and treatment options assumed to be the same

4 Receptor discordance between primary and recurrence: –Mostly retrospective. –Utilized pathology reports – did not re-analyze samples. –Rates of discordance for receptor determination: Hormone receptors % HER % Relative uniformity of hormone receptor expression between different metastatic sites. Current knowledge Wu et al. Clin Cancer Res ;

5 Is discordance important? Discordance may be associated with poorer survival. Suggested reasons include: –Inappropriate use of targeted therapies –Selection of tumors with higher propensity for resistance to systemic therapy Liedke et al. Ann Oncol 2009; 20: 1953–1958. Concordant receptors Discordant receptors

6 Limitations of Retrospective Studies Inconsistent techniques Inter-laboratory variability Inter-observer variability Variability in patient/sample collection No assessment of impact on clinical management Feasibility & patient acceptability not assessed

7 Important questions Is discordance “real”? –A change in biology or manifestation of measurement “error”? Is the source of discordance important? –Clinicians use receptor status to plan therapy. –Discordance important irrespective of its underlying etiology? Barry et al. J Clin Oncol 2010; 28: Weigelt et al. Lancet Oncol 2010; 11:

8 Study Designs DESTINY Study: –Single center study, Toronto Canada –ER/PgR by IHC using ASCO guidelines –HER2 FISH –Re-analysis of primary BRITS Study –Multi-center study, UK –ER/PgR by IHC using quantitative and Allred methods –HER2 FISH –Re-analysis of primary BIOPSY OF RECURRENCE Central pathology review Evaluation of ER/PgR/HER2 Oncologist: post-biopsy questionnaire Oncologist: pre-biopsy questionnaire Written informed consent Suspected recurrence or progression

9 Endpoints Primary Endpoint: –The proportion of patients in whom the results of the recurrence biopsy led to a change in management. Secondary Endpoint: –Discordance rates in ER, PgR and HER2 between primary and recurrence. Exploratory Analysis: –Evaluate the effect of baseline tumor characteristics and time on both receptor status and change of management.

10 Patient Demographics n=271

11 Location of biopsies

12 Change in therapy Among 271 patients: –41 (15.1%) had a change in therapy –1 change in systemic therapy for every 6.6 biopsies –95% CI = 11.1 – 20.0% –P < Loco-regional recurrence 13.8% 10%20%30% < P Value 17.0% Distant recurrence Whole study population

13 Change in therapy Common reasons for change in management: –Changes in HER2. –Gain of hormone receptor. –Identification of benign disease or second malignancy.

14 Receptor Concordance There are 2 different criteria for defining positivity among ER and PgR: –ASCO suggest any staining in >1% of cancer cells is positive. –St. Gallen (Europe) suggest staining in >10% of cancer cell is positive. Discordance was defined as: –A change from positive to negative (or vice versa). –NOT a quantitative change in receptor expression.

15 Receptor Concordance 4 cases

16 Absolute change in receptor expression Receptors concordant Receptors discordant Increase in receptor expression from primary to recurrence Decrease in receptor expression from primary to recurrence

17 Re-analysis of primary Receptor discordance in: –ER - 5.8%, –PgR %, –HER %

18 Exploratory Analyses Rate of receptor discordance in triple negative tumors is very low (6.8% v 44.9%). Duration between primary and recurrence biopsies does not appear to influence receptor discordance. –t-test 0.917, p=0.360

19 Potential Harms Experience from a single institution (n=121): –Median delay to treatment was 15 days (range 2-56). –One procedure-related serious adverse event: Uncontrollable bleeding from a skin punch biopsy site. –Patient reported outcomes: Anxiety % Pain % –87.8% stated they would recommend a biopsy of their recurrence to other patients.

20 Conclusions Variability in receptor staining is well recognized. Largest prospective analysis of receptor status in matched primary and recurrent breast cancer. Substantial discordance in receptors: –Most common in hormone receptors; –Less common in HER2; –Least common in triple negative. Taucher et al. Endocr Relat Cancer ; Weigelt et al. Lancet Oncol 2010; 11:

21 Conclusions The number needed to biopsy to alter immediate patient management was 6.6. Biopsy should be considered to confirm disease recurrence in breast cancer.

22 Acknowledgements DESTINY Study Christine Simmons Htway Maung Aurora De Borja Farrah Kassam Julie Napolskikh Bill Geddie George Dranitsaris CBCF-Ontario BRITS Study Colin Purdie Lee Jordan Phil Quinlan Tayside Tissue Bank Breast Cancer Research (Scotland) AstraZeneca (UK)


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