320P - Clinical and pathological characteristics of breast cancers switching from early luminal-like to metastatic triple-negative phenotype

Background

Loss of hormone receptors (HR) at breast cancer (BC) metastatic relapse has been reported. Few data are available on the clinicopathologic features associated with HR loss and its prognostic impact.

Methods

We retrospectively identified a cohort of 51 patients (pts) with primary HR+/HER2- BC and triple-negative (TN) metastasis (LUM-TN) along with two control cohorts of paired HR+/HER2- and TN on both primary and metastatic samples (LUM-LUM, n=50; TN-TN, n=49). Clinical features and outcomes were retrieved from medical charts. HR and HER2 status were independently reviewed by two pathologists on all archival samples. Estrogen receptor (ER) expression between 1% and 10% was considered as ER-low. Cox-proportional hazard models were used to assess the impact of variables on distant metastasis-free survival (DMFS) and overall survival (OS).

Results

The three cohorts had no difference in median age, menopausal status nor stage at diagnosis. Pts in LUM-TN cohort had a higher frequency of invasive lobular (20% vs 10% vs 2%, p=.03), primary ER-low BCs (22% vs 0% vs 0%, p<.001) and locoregional relapse (18% vs 0% vs 2%, p<.001) than pts in the LUM-LUM and TN-TN cohorts. Metastatic samples from pts in LUM-TN and LUM-LUM cohorts were more frequently HER2-low than those in TN-TN cohort (57% vs 66% vs 24%, p<.001). At univariate analysis, pts with LUM-TN switch had a longer DMFS compared to the TN-TN (median DMFS 62 vs 18 months; HR 3.35, 95%CI 2.2-5.1, p<.001), but similar to the LUM-LUM cohort (median DMFS 62 vs 64 months; HR 0.95, 95%CI 0.6-1.41, p<.8). The DMFS difference was not significant after adjusting for other variables, including grade and ER-low status. Median OS was significantly lower for pts in LUM-TN (median OS 93 vs 139 months; HR 2.3, 95%CI 1.3-4.1, p<0.004) and TN-TN cohorts (median OS 47 vs 139 months; HR 3.4, 95%CI 1.1-10.7, p<0.03) when compared to the LUM-LUM cohort, independently from other clinicopathologic features.

Conclusions

HR loss at metastatic relapse is frequent in lobular and ER-low primary BCs. Pts with HR loss have similar DMFS compared to pts with maintained HR expression, but apparently reduced OS. Further investigation on biological mechanisms underpinning the LUM-TN phenotype switch is ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fondazione Umberto Veronesi, Fondazione IEO – MONZINO, Italian Ministry of Health with Ricerca Corrente 5 x 1000.

Disclosure

M. Ivanova: Financial Interests, Institutional, Research Funding: Fondazione Umberto Veronesi. K. Venetis: Financial Interests, Institutional, Research Funding: Fondazione IEO – MONZINO. G. Curigliano: Financial Interests, Institutional, Speaker, Consultant, Advisor: Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche, Seagen, Daiichi Sankyo. N. Fusco: Financial Interests, Institutional, Speaker, Consultant, Advisor: MSD, Boehringer Ingelheim, Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Funding: Italian Ministry of Health with Ricerca Corrente 5 x 1000 funds. C. Criscitiello: Financial Interests, Institutional, Speaker, Consultant, Advisor: Pfizer, Lilly, Novartis, Roche, Bristol Myers Squibb, Seagen, Daiichi Sankyo. All other authors have declared no conflicts of interest.