Follow-up subsequent to the date of initial interview and covariate data (age at diagnosis, study center, education level, BMI and months since last full-term pregnancy) were available for 3,107 (98%) of 3,159 eligible women, and of these 567 (18%) had died. Median follow-up was 8.5 years. Subject and tumor characteristics are described in . presents estimated hazard ratios and 95% confidence intervals for the associations between pre-diagnosis reproductive variables and all-cause mortality from both unadjusted and adjusted analyses.
Hazard ratio (HR) estimates and 95% confidence intervals (CI) for death (all causes) following breast cancer diagnosis associated with reproductive factors prior to diagnosis in unadjusted and adjusted analyses.
Based on unadjusted analyses, having had a recent full-term pregnancy prior to breast cancer diagnosis was associated with poorer survival. Compared with nulliparous women, those who had had a full-term pregnancy within 2 years prior to their breast cancer diagnosis, or within 2 to 5 yrs prior, were more likely to die (HR=2.75, 95%CI=1.98–3.83, p<0.001 and HR=2.20, 95%CI=1.65–2.94, p<0.001, respectively). Mortality was also associated with shorter time since last OC use (HR=0.71 per decade, 95%CI=0.62–0.80, p<0.001) and OC use before age 20 years (HR=1.27, 95%CI=1.02–1.58, p=0.03).
From adjusted analyses, poorer survival was associated only with time from last full-term pregnancy to diagnosis (). Compared with nulliparous women, those who had had a child within 2 years prior to their breast cancer diagnosis, or within 2 to 5 years prior, were more likely to die (HR=2.25, 95%CI=1.59–3.18, p<0.001 and HR=1.82, 95%CI=1.35–2.46, p<0.001, respectively). This association was further examined by plotting HR estimates and their floating 95% confidence intervals in smaller categories of time from last full-term pregnancy to diagnosis (). This confirmed that most of the excess mortality above that for nulliparous women was for parous women who developed breast cancer within 6 years of their last full-term pregnancy, with the highest risk seen for those who developed breast cancer within 2 years of their last full-term pregnancy, and there was virtually no excess risk beyond 6 years.
Figure 1 HR estimates, with floating 95% confidence intervals, relative to nulliparous women, by categories of time between last full-term pregnancy and breast cancer diagnosis. Categories considered are defined by the values labeled on the x-axis, with lower (more ...)
Sensitivity analyses showed that the association between all-cause mortality and time between last full-term pregnancy and breast cancer diagnosis became slightly stronger when restricted to the 2,404 women who tested negative for metastases at diagnosis, with adjusted HR estimates of 2.39 (p<0.001) and 2.11 (p<0.001) for <2 years and 2 to 5 years since last full-term pregnancy, respectively). The same pattern of risk was also observed after including tumor characteristics and treatment within the first year after diagnosis in the adjusted analyses, based on the 1,826 women with complete data (HR=1.97, p=0.04 and HR=2.55, p=0.001, respectively).
The statistically significant unadjusted associations between OC use variables and mortality were no longer evident after adjustment for established determinants of mortality. The apparent association appeared to be due to confounding of OC use with age and time since last full-term pregnancy. After adjustment, the HR per decade for time since last OC use became 0.91, 95% CI=0.74–1.11, p=0.3, and the HR for OC use before age 20 years became 1.04, 95% CI=0.81–1.33, p=0.7. There were no statistically significant associations between all-cause mortality and any of the other pre-diagnosis reproductive factors from either the unadjusted or adjusted analyses, although for menopausal status there was a nominally significant association, but only after adjustment for age, and this disappeared once an additional adjustment was made for treatment, in particular chemotherapy. This may therefore represent a false positive association.