Tumor-infiltrating lymphocytes (TILs) in paired samples from patients with phenotypic switch from early luminal-like to metastatic triple-negative breast cancer

Background Loss of Hormone Receptors (HR) at metastatic (met) relapse has been widely described in breast cancer (BC). Higher TILs have been associated with better prognosis in patients (pts) with early triple-negative (TN) BC, but to worse outcome in HR-positive (HR+)/HER2- BC. TILs significance in pts with HR-loss has never been investigated. Methods We retrospectively identified a cohort of 58 pts with early HR+/HER2- (eHR+) and paired met TN (mTN) BC. Archival tissue of both eHR+ and mTN samples were retrieved and analyzed. Samples with estrogen receptor (ER) >=1% were considered as HR+, and ER 1-10% as ER-low. TILs were scored as continuous variable by two pathologists. We correlated collected variables with distant metastasis-free survival (DMFS), overall survival (OS; time from BC diagnosis to death) and met-OS (time from met relapse to death). Results Median age at diagnosis was 51 (34-80). Median ER level was 72% (IQR, 30-90%), with 11 (19%) ER-low cases. Median TILs (mTILs) on eHR+ was 15 (IQR, 5-30). 13 pts (22%) had locoregional relapse, which was HR+ in 8 pts. 44 (76%) and 52 (90%) pts received chemo- and hormone-therapy, respectively, before met relapse. 34 pts (59%) were biopsied at first met relapse, 26% and 15% of pts received 1-2 or >=3 therapy lines prior to sampling, respectively. Most frequent biopsy sites were liver (28%), skin (19%), pleura (14%), bone (10%). mTILs on mTN was 3 (IQR, 0-18), which was lower than on the paired eHR+ (p<0.01). mTILs significantly differed across sites (mTILs=0 in bone, liver, skin; mTILs >=15 in lung, pleura, peritoneum, soft tissue). Median DMFS, met-OS and OS were 4.2 (IQR, 1.4-7.8), 2.4 (IQR, 1.6-3.4) and 7.2 (IQR, 4-10) yrs, respectively. TILs as continuous variable on eHR+ were independently associated with shorter DMFS (p<0.01) and OS (p=0.01), but mTILs did not (p>0.1). ER-low status also correlated with shorter DFMS (p=0.03). No other variables did significantly correlate with outcomes. Conclusions Prognosis of pts with luminal-to-TN switch appears to be intermediate between the two subtypes. Lower TILs scores are observed at met relapse, with differences across sites. According to our data, higher TILs on eHR+ seems to correlate with worse outcome.