1143 – Genetic and model-based risk stratification reshapes clinical management in women considering hormone replacement therapy

Authors

  • Jennifer Thalita Targino dos Santos Oncologia D’Or - Ribeirão Preto (SP), Brazil.
  • Daniela Borges da Rocha Macedo Oncologia D’Or - Ribeirão Preto (SP), Brazil.
  • Pilar Barreto de Araújo Porto Oncologia D’Or - Ribeirão Preto (SP), Brazil.
  • Isabela Bussade Coelho da Rocha Oncologia D’Or - Ribeirão Preto (SP), Brazil.
  • Alison Luis Eburneo Pereira Oncologia D’Or - Ribeirão Preto (SP), Brazil.
  • Rodrigo Santa Cruz Guindalini Oncologia D’Or - Ribeirão Preto (SP), Brazil.

DOI:

https://doi.org/10.29289/25945394V36S11143

Keywords:

hormone replacement therapy, genetic risk score, breast neoplasms, hereditary breast and ovarian cancer syndrome, precision medicine

Abstract

Introduction: Hormone replacement therapy (HRT) effectively relieves menopausal symptoms, yet its association with
breast cancer (BC) risk varies substantially by regimen and individual genetic susceptibility. In Brazil, HRT has also been
utilized in less studied formulations, such as subcutaneous gestrinone implants. To our knowledge, no previous study
has systematically examined the impact of integrating genetic counseling (GC) and genomic risk modeling specifically
within the HRT decision-making context.
Methods: A retrospective cohort study of 144 women referred to a Brazilian private oncogenetics service between
September 2022 and May 2025 for BC risk assessment related to HRT initiation or continuation. Genetic testing followed
2025 NCCN criteria; however women that did not meet the formal criteria could still undergo testing after shared decision-making. Clinical recommendations were based on CanRisk v3.0.0 thresholds for MRI surveillance, chemoprevention, and risk-reducing surgery.
Results: Among 144 women (mean age: 51 years), 135 underwent genetic testing. Fourteen (10.4%) carried pathogenic
variants in BC susceptibility genes, including BRCA1/2, PALB2, ATM, CHEK2, RAD51C/D, and BARD1. The integration of
GC and CanRisk changed clinical management in 29 patients (21.5%). Chemoprevention recommendations were modified in 13 women (9.7%), and MRI surveillance recommendations changed in 13 (9.6%). In addition, 9 women (6.7%) received
new recommendations for risk-reducing surgery due to high-penetrance variants. Notably, one prophylactic mastectomy
revealed early-stage ductal carcinoma in situ.
Conclusion: The HRT consultation may represent a valuable opportunity to identify women with unrecognized hereditary BC risk and refine prevention strategies. To our knowledge, this is the first Brazilian study to integrate personal and
family history, germline testing, and CanRisk modeling within the HRT decision-making context. These findings propose
a structured, risk-stratified pathway for managing this population, a novel paradigm to be further validated in larger,
multicenter cohorts.
Ethics: CAEE 88951825.5.0000.5249.

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Published

2026-10-19

How to Cite

dos Santos, J. T. T., Macedo, D. B. da R., Porto, P. B. de A., da Rocha, I. B. C., Pereira, A. L. E., & Guindalini, R. S. C. (2026). 1143 – Genetic and model-based risk stratification reshapes clinical management in women considering hormone replacement therapy. Mastology, 36(suppl. 1). https://doi.org/10.29289/25945394V36S11143

Issue

Vol. 36 No. suppl. 1 (2026)

Section

Basic Research Section

License

Copyright (c) 2026 Jennifer Thalita Targino dos Santos, Daniela Borges da Rocha Macedo, Pilar Barreto de Araújo Porto, Isabela Bussade Coelho da Rocha, Alison Luis Eburneo Pereira, Rodrigo Santa Cruz Guindalini

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.