Abstract 243P
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Stefania Morganti is supported by: American-Italian Cancer Foundation; AIRC; Fondazione Bonadonna.
Disclosure
G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences; Financial Interests, Personal, Advisory Board, Advisory Board: Exact Science, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA. N. Fusco: Financial Interests, Personal, Invited Speaker: MSD, Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo, GSK; Financial Interests, Personal, Advisory Board: MSD, Boehringer Ingelheim, GSK; Financial Interests, Personal and Institutional, Advisory Board: Novartis. C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli-Lilly, Roche; Financial Interests, Personal, Advisory Board: MSD, Seagen. All other authors have declared no conflicts of interest.