6 research outputs found
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] Œ 0.99, 95% confidence interval [CI] Œ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRcŒ 0.79, 95% CI Œ 0.69 to 0.91; HRcŒ 0.70, 95% CI Œ 0.59 to 0.82; HRcŒ 0.50, 95%
CI Œ 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 Œ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers
were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] Œ 1.69, 95% CI Œ 1.09 to 2.62). For BRCA2
mutation carriers, being parous was associated with a 30% increase in BC risk (HRc Œ 1.33, 95% CI Œ 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 (HRcŒ 0.72, 95%
CI Œ 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
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Coronary Artery Calcification (CAC) and PostâTrial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) EstrogenâAlone Trial
Background: Among women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) EstrogenâAlone (EâAlone) trial, randomization to conjugated equine estrogenâalone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHIâCACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography â8.7 years after baseline randomization. We hypothesized that higher CAC would be related to postâtrial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors. Methods and Results: WHIâCACS participants (n=1020) were followed â8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low ageâadjusted rates/1000 personâyears of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were â2âfold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogenâalone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality. Conclusions: Among a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI EâAlone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over â8 years, independent of baseline randomization to conjugated equine estrogenâalone versus placebo or CVD risk factors. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611