Copy number heterogeneity identifies ER+ breast cancer patients that do not benefit from adjuvant endocrine therapy

Br J Cancer. 2022 Oct;127(7):1332-1339. doi: 10.1038/s41416-022-01906-3. Epub 2022 Jul 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Chemotherapy, Adjuvant
  • DNA Copy Number Variations
  • Estrogens / therapeutic use
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Receptors, Estrogen
  • Retrospective Studies


  • Antineoplastic Agents, Hormonal
  • Estrogens
  • Receptors, Estrogen