Although 1% is the recommended cutoff for defining triple-negative breast cancer (TNBC), growing evidence suggests that 10% cutoff may better recapitulate TNBC. Conversion to TNBC at relapse is associated with poor survival. We primarily aim to assess the prognostic impact of phenotypic conversion to estrogen receptor (ER)-low BC in patients experiencing relapse.
Relapsing BC patients from two Institutions were included. Patients were categorized in: TNBC (ER=0%, HER2-0/low), ER-low (ER=1-9%, HER2-0/low), Luminal (ER=10-100%, HER2-0/low), HER2+. Overall survival (OS) and post-relapse survival (PRS) were adopted as endpoints.
877 patients were included. The proportion of ER-low tumors was 3.2% on primary BC and 2.9% on relapse. When assessing the prognostic impact of primary BC phenotype, TNBC and ER-low retained a similar and significantly poorer prognostic impact than Luminal and HER2+ BC. In detail, median OS [mos] was: TNBC 68.6, ER-low 47.6, Luminal 125.4, HER2+ 121.4, p<0.001). PRS analysis described the same phenomenon (p<0.001) Superimposable findings were observed when considering the prognostic impact of tumor phenotype at relapse (OS, p<0.001; PRS, p<0.001). At relapse, 6.4% of TNBC, 2.5% of Luminal and 1.9% of HER2+ primary BC cases switched to ER-low phenotype (overall conversion rate to ER-low BC: 2.8%). Among Luminal BC patients, those converting to ER-low at relapse showed the worst outcome, with poorer survival than those maintaining Luminal BC or converting to either TNBC or HER2+. In detail, median OS [mos] was: concordant Luminal 134.7, conversion to ER-low 54.4, conversion to TNBC 80.4, conversion to HER2+ 129.9, p<0.001; median PRS [mos] was: concordant Luminal 51.4, conversion to ER-low 12.4, conversion to TNBC 29.6, conversion to HER2+ 44.4, p<0.001.
ER-low BC was associated with unfavorable prognosis, similar to TNBC and significantly poorer than Luminal and HER2+. Luminal BC patients converting to ER-low phenotype experienced the worst survival rates, even worse than those converting to TNBC, possibly due to the limited access to TNBC treatment algorithms. Our study supports the assimilation of ER-low BC to TNBC.
The authors.
Fondazione AIRC under 5 per mille 2019 - ID. 22759 program, DOR funding from the University of Padua.
F. Miglietta: Financial Interests, Personal, Invited Speaker, outside the submitted work: Novartis, Roche, Gilead. G. Griguolo: Financial Interests, Personal, Advisory Board, outside the submitted work: Gilead; Financial Interests, Personal, Speaker’s Bureau, outside the submitted work: Lilly, Novartis; Financial Interests, Personal, Other, outside the submitted work: Pfizer, Amgen, Daiichi Sankyo/AstraZeneca. T. Giarratano: Financial Interests, Personal, Invited Speaker, outside the submitted work: Roche, Novartis, Lilly. F. Girardi: Financial Interests, Personal, Invited Speaker, outside the submitted work: AstraZeneca; Financial Interests, Personal, Other, outside the submitted work: Lilly, Gilead, Takeda. C.A. Giorgi: Financial Interests, Personal, Invited Speaker, outside the submitted work: Novartis. M. Fassan: Financial Interests, Personal, Advisory Board, outside the submitted work: Astellas Pharma, GlaxoSmithKline, Roche, MSD Oncology, AstraZeneca, Pierre Fabre; Financial Interests, Personal, Research Grant, outside the submitted work: QED Therapeutics, Macrophage Pharma, Diaceutics. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Amgen, GSK; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Sanofi, merck serono, Exact Sciences, Eisai, Olema Oncology; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, Glaxo Smith kline, Daiichi Sankyo, Nerviano; Non-Financial Interests, Member: ASCO. M.V. Dieci: Financial Interests, Personal, Advisory Board, outside the submitted work: Lilly, Novartis, Exact Sciences, Pfizer, Seattle Genetics, MSD, Gilead Sciences; Financial Interests, Institutional, Other, outside the submitted work: Patent pending HER2DX licensed to University of Padova. All other authors have declared no conflicts of interest.