3 research outputs found
Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer
Introduction Cardiovascular disease (CVD) is an
important cause of death in breast cancer survivors.
Some breast cancer treatments including anthracyclines,
trastuzumab and radiotherapy can increase the risk of
CVD, especially for patients with pre-existing CVD risk
factors. Early identification of patients at increased CVD
risk may allow switching to less cardiotoxic treatments,
active surveillance or treatment of CVD risk factors. One of
the strongest independent CVD risk factors is the presence
and extent of coronary artery calcifications (CAC). In
clinical practice, CAC are generally quantified on ECGtriggered cardiac CT scans. Patients with breast cancer
treated with radiotherapy routinely undergo radiotherapy
planning CT scans of the chest, and those scans could
provide the opportunity to routinely assess CAC before a
potentially cardiotoxic treatment. The Bragatston study
aims to investigate the association between calcifications
in the coronary arteries, aorta and heart valves (hereinafter
called ‘cardiovascular calcifications’) measured
automatically on planning CT scans of patients with breast
cancer and CVD risk.
Methods and analysis In a first step, we will optimise
and validate a deep learning algorithm for automated
quantification of cardiovascular calcifications on
planning CT scans of patients with breast cancer.
Then, in a multicentre cohort study (University Medical
Center Utrecht, Utrecht, Erasmus MC Cancer Institute,
Rotterdam and Radboudumc, Nijmegen, The Netherlands),
the association between cardiovascular calcifications
measured on planning CT scans of patients with breast
cancer (n≈16 000) and incident (non-)fatal CVD events
will be evaluated. To assess the added predictive value of
these calcifications over traditional CVD risk factors and
treatment characteristics, a case-cohort analysis will be
performed among all cohort members diagnosed with a
CVD event during follow-up (n≈200) and a random sample
of the baseline cohort (n≈600).
Ethics and dissemination The Institutional Review
Boards of the participating hospitals decided that the
Medical R
The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations
Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at
increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether
the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.
Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events
are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers)
and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.
Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined
hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95%
CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated
with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers
were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2
mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there
was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95%
CI ¼ 0.54 to 0.98).
Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with
higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers