Changes in hormone-receptor status in luminal breast cancers between primary tumour and metastases: Results of the observational cohort GIM-13 AMBRA study

Background Tumor phenotype may change during breast cancer (BC) progression and discordance between primary and metastases ranges between 16% and 21% for Hormone Receptor (HR) expression in some series. The impact of this change on patient (pts) management and outcome is not yet clear, even though preliminary data indicate that the molecular characterization of recurrent breast cancer may induce clinicians to modify the treatment choice in ∼14% of the cases and that a change in the receptor status is associated with poorer survival. This analysis evaluates the prognostic impact of receptor discordance between paired primaries and recurrences. Methods We used data of 879 pts of the longitudinal cohort AMBRA study, identifying 3 different groups: Group A: HR+ BC remaining HR+ at relapse; Group BHR+ BC becoming TNBC; Group C:TNBC remaining TNBC. Change in HR status was evaluated on the biopsy done at the moment of relapse. Time to event was evaluated by Cox-Mantel Hazard Ratio and Logrank Test; Mean/median by Wilcoxon Rank-Sum Test. Results Pts who underwent biopsy at the time of relapse were 545/879 (62%), of those 462 (84.4%) were classified as Luminal tumors and 83 (15.2%) TNBC on primary. Change in tumor phenotype occurred in 31 (6.7%) of Luminal BC and 16 (19.3%) TNBC, probably due to a higher genomic instability (p = 0.021). Median DFS between Luminal BC was not different: HR+aHR+: 74.56 months (95%CI 66.8-82.1) vs HR+aTNBC: 89.73 months (95%CI:44.73-103.46). Table summarizes main data in time to event in the 3 identified groups. *PFS at 1strelapse; **PFS at 2nd relapse; ***Time to Treatment Change at 1strelapse; °OS at 1strelapse; §OS from 1stPD. Table . 325P HR+/HR + (range) Group A HR+/TNBC (range) Group B p value Group A vs C TNBC/TNBC (range) Group C PFS1* (months) 13.65 (0,77-162,03) 9.45 (3,97-52,73) 0.36 8.13 (6.3-10.9) PFS2** (months) 6.83 (0,00-57,13) 6.12 (2,67-26,30) 0.84 4.20 (0,33-22,17) TTC1*** (months) 12.43 (0,13-163,10) 8.88 (0,00-48,40) 0.50 7.88 (0,23-27,80) TTC2**** (months) 7.45 (0,00-55,97) 6.73 (3,77-26,80) na na OS1° (months) 23.1 (20-26) 15 (8.7-26.3) 0.031 3.60 (0,60-25,38) OS (years) 8.52 (0,26-115,92) 7.86 (0,19-30,67) 0.43 3.58 (2.91-2.39) OS from PD1§ (months) 25.8 (0,00-207,53) 17.23 (2,67-104,30) 0.82 17.90 (2,37-53,57) Conclusions Change in tumor phenotype has a significant impact on OS; BC pts who become TNBC at relapse should be treated in the same way as TNBC pts at diagnosis. Anyway, OS of Luminal BC who change phenotype seems to be better than TNBC. Legal entity responsible for the study GIM - Gruppo Italiano Mammella. Funding Celgene. Disclosure All authors have declared no conflicts of interest.