Annual Meeting of the NCI Cohort Consortium (Abstract Submission): Submission #13

Submission information
Submission Number: 13
Submission ID: 151076
Submission UUID: ff8fc90e-5f3d-453d-83f7-a899287d4ccb

Created: Fri, 09/05/2025 - 16:53
Completed: Fri, 09/05/2025 - 16:53
Changed: Fri, 09/05/2025 - 16:53

Remote IP address: 10.208.24.102
Submitted by: Anonymous
Language: English

Is draft: No
Lightning Talks Abstract
Reuben
Frost
{Empty}
MMath
The Institute of Cancer Research
Adding serum hormone measurement to improve the Tyrer-Cuzick breast cancer risk model in postmenopausal women
  1. First Name: Tahania
    Last Name: Ahmad
    Degree(s): Ph.D.
    Organization: Queen Mary University of London
  2. First Name: Anne
    Last Name: MacGregor
    Degree(s): M.D.
    Organization: Queen Mary University of London
  3. First Name: Heather
    Last Name: Eliassen
    Degree(s): Sc.D.
  4. First Name: Susan
    Middle Initial: E
    Last Name: Hankinson
    Degree(s): Sc.D.
  5. First Name: Roger
    Middle Initial: L
    Last Name: Milne
    Degree(s): Ph.D.
    Organization: Cancer Council Victoria
  6. First Name: Celine
    Middle Initial: M
    Last Name: Vachon
    Degree(s): Ph.D.
  7. First Name: Amy
    Last Name: Berrington
    Degree(s): Ph.D.
    Organization: The Institute of Cancer Research
  8. First Name: Adam
    Last Name: Brentnall
    Degree(s): Ph.D.
    Organization: Queen Mary University of London
  9. First Name: Jack
    Last Name: Cuzick
    Degree(s): Ph.D.
    Organization: Queen Mary University of London
  10. First Name: Judith
    Last Name: Offman
    Degree(s): Ph.D.
    Organization: Queen Mary University of London
  11. First Name: Montserrat
    Last Name: García-Closas
    Degree(s): M.D.
    Organization: The Institute of Cancer Research
Introduction: The primary objective is to evaluate the potential of incorporating the ratio of serum estradiol (E2) and sex hormone binding globulin (SHBG) into breast cancer risk assessments using the Tyrer-Cuzick (T-C) breast cancer risk prediction model. Currently there is limited research on their integration in individual risk assessments.

Methods: E2/SHBG levels will be added to the current T-C model, using a two-stage process applied to data from 2,666 cases (invasive breast cancers) and 4,512 non-cases from three nested case-control studies and one case-cohort study, all part of the B2RISK consortium to:
(1) develop a statistical model to explain variation in E2 and SHBG levels based on factors in the T-C model; and
(2) estimate the odds ratio with the "hormone residual" (i.e., observed minus expected E2/SHBG from (1)), adjusted for T-C 10-year risk.
The model will be validated in the Breast Cancer Now Generations (BGS) prospective cohort in the UK including 42,075 eligible participants, 847 with incident breast cancer diagnosed within a 5-years follow-up.

Results: Calibration of the current T-C model has been assessed in a BGS nested case-control sample with data on classical risk factors, 313-SNP polygenic risk score and mammographic density (1,777 controls and 610 breast cancer cases), using 5-year risk scores generated by T-C model v8 before adding hormones. The model was well calibrated (calibration slope 1.0 (95%CI 0.67-1.30) with an age-adjusted AUC=0.65 (95%CI 0.62-0.68).

Conclusion: T-C scores are well calibrated with modest risk discrimination. Further analyses will evaluate whether adding E2/SHBG improves the model.