TY - JOUR
T1 - Copy number heterogeneity identifies ER+ breast cancer patients that do not benefit from adjuvant endocrine therapy
AU - van den Bosch, Tom
AU - Rueda, Oscar M.
AU - Caldas, Carlos
AU - Vermeulen, Louis
AU - Miedema, Daniël M.
N1 - Funding Information: This work was supported by Amsterdam UMC and Oncode; a talent development grant of the AG&M institute of Amsterdam UMC and a Young Investigator Grant of KWF (12215) to DMM. The funders had no role in study design or manuscript submission. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/10/19
Y1 - 2022/10/19
N2 - Background: Endocrine therapy forms the backbone of adjuvant treatment for oestrogen-receptor-positive (ER+) breast cancer. However, it remains unclear whether adjuvant treatment improves survival rates in low-risk patients. Low intra-tumour heterogeneity (ITH) has been shown to confer low risk for recurrent disease. Here, it is studied if chromosomal copy-number ITH (CNH) can identify low-risk ER+, lymph-node-negative breast cancer patients who do not benefit from adjuvant endocrine therapy. Methods: Lymph-node-negative ER+ patients from the observational METABRIC dataset were retrospectively analysed (n = 708). CNH was determined from a single bulk copy-number measurement for each patient. Survival rates were compared between patients that did or did not receive adjuvant endocrine therapy for CNH-low, middle and high groups with Cox proportional-hazards models, using propensity-score weights to correct for confounders. Results: Adjuvant endocrine therapy improved the relapse-free survival (RFS) for CNH-high patients treatment (HR = 0.55), but not for CNH-low patients treatment (HR = 0.88). For CNH-low patients adjuvant endocrine therapy was associated with impaired OS (HR = 1.62). Conclusions: This retrospective study of lymph-node-negative, ER+ breast cancer finds that patients identified as low risk using CNH do not benefit from adjuvant endocrine therapy.
AB - Background: Endocrine therapy forms the backbone of adjuvant treatment for oestrogen-receptor-positive (ER+) breast cancer. However, it remains unclear whether adjuvant treatment improves survival rates in low-risk patients. Low intra-tumour heterogeneity (ITH) has been shown to confer low risk for recurrent disease. Here, it is studied if chromosomal copy-number ITH (CNH) can identify low-risk ER+, lymph-node-negative breast cancer patients who do not benefit from adjuvant endocrine therapy. Methods: Lymph-node-negative ER+ patients from the observational METABRIC dataset were retrospectively analysed (n = 708). CNH was determined from a single bulk copy-number measurement for each patient. Survival rates were compared between patients that did or did not receive adjuvant endocrine therapy for CNH-low, middle and high groups with Cox proportional-hazards models, using propensity-score weights to correct for confounders. Results: Adjuvant endocrine therapy improved the relapse-free survival (RFS) for CNH-high patients treatment (HR = 0.55), but not for CNH-low patients treatment (HR = 0.88). For CNH-low patients adjuvant endocrine therapy was associated with impaired OS (HR = 1.62). Conclusions: This retrospective study of lymph-node-negative, ER+ breast cancer finds that patients identified as low risk using CNH do not benefit from adjuvant endocrine therapy.
UR - http://www.scopus.com/inward/record.url?scp=85134543920&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41416-022-01906-3
DO - https://doi.org/10.1038/s41416-022-01906-3
M3 - Article
C2 - 35864159
SN - 0007-0920
VL - 127
SP - 1332
EP - 1339
JO - British journal of cancer
JF - British journal of cancer
IS - 7
ER -