A total of 5,012 eligible women were interviewed. After omitting respondents who could not be analyzed for associations between reproductive factors and breast cancer (162 women with incomplete interviews or poor data quality, 12 women who did not provide information about pregnancies, and two who reported never menstruating), there were 796 HISP cases, 919 HISP controls, 1,525 NHW cases, and 1,596 NHW controls available for analysis (). HISP controls had lower educational attainment than NHW controls (p < 0.0001). Participating HISP cases differed from NHW cases on distributions of certain clinical and pathological variables, having higher proportions with regional or distant stage at diagnosis, and with tumors larger than 2 cm in diameter. The difference in distribution of stage at diagnosis by ethnicity was also present when comparisons were made for all eligible cases for whom data were available, including nonparticipants: among all eligible HISP cases, the percentages with in situ, local, and regional/distant disease at diagnosis were 15.1%, 47.8%, and 37.1%, whereas among eligible NHW cases, the corresponding percentages were 16.5%, 53.8%, and 29.7% (p = 0.0003). The two ethnic groups did not differ on tumor histologies, or grade, but, among cases with known ER status, the fraction with ER negative tumors was higher among Hispanics, 26.3%, than non-Hispanic whites. 19.6% (p = 0.03 for difference by ethnicity, age-adjusted).
Characteristics of Hispanic and non-Hispanic white breast cancer cases and controls, 4 Corners Study
A trend of lower breast cancer risk with older age at menarche was only weakly apparent among HISP women, with an OR of 0.85 (95% CI: 0.64, 1.13) for women reporting menarche at age 14 or older compared to age 11 or younger (). The contrast in breast cancer risk between the oldest and youngest age at menarche categories was stronger among NHW women, with an OR of 0.69 (95% CI: 0.55, 0.86) and a significant trend (p = 0.003), but there was no evidence of heterogeneity of effect by ethnicity (p interaction = 0.57). These trends were similar when pre- and peri-menopausal women were considered separately from post-menopausal women.
Reproductive history risk factors for breast cancer in Hispanic and non-Hispanic white women, 4 Corners Study
Hispanic women with a first birth at age 30 or older had an approximately twofold increased risk of breast cancer compared to women with a first birth before age 20 (). The association was somewhat more apparent in premenopausal women, with an OR of 2.66 (95% CI: 1.41, 5.02), compared to an OR of 1.56 (95% CI: 0.88, 2.75) in the post-menopausal subgroup (). Nulliparous HISP women had an estimated 30% higher breast cancer risk than women with a first birth before age 20, a non-significant difference. There was little evidence of a trend in breast cancer risk with age at first birth in the NHW study population. NHW in this study included a high proportion who were current users of post-menopausal hormones [4
], an exposure that modifies the effects of other breast cancer risk factors. When recent users of estrogen or estrogen plus progestin post-menopausal hormones were excluded, there was some evidence of a trend of increasing breast cancer risk with older age at first birth among the remaining NHW women (p
= 0.07), with an OR of 1.21 (95% CI: 0.82, 1.79) for a first birth at age 30 or older relative to women with a first birth before age 20. The proportion of HISP controls who did not have a first birth before age 20 was 0.739, whereas for non-Hispanic whites, the proportion was 0.863. The population attributable risk percents associated with not having a first birth before age 20 are estimated to be 7.7% for HISP and 9.9% for non-Hispanic whites, a 2.2% difference between the two ethnic groups.
Reproductive history risk factors for breast cancer in Hispanic and non-Hispanic white women by menopausal status, 4 Corners Breast Cancer Study
Hispanic women with five or more births had a reduced risk of breast cancer, OR 0.70 (95% CI: 0.50, 0.98) compared to those with one or two births (); the protective effect was similar to that observed for the same comparison among NHW women, OR 0.56 (95% CI: 0.41, 0.75). The ORs for five or more births were 0.83 (0.40, 1.72) for pre-menopausal and 0.66 (0.44, 0.97) for post-menopausal HISP women (). The trend of increasing breast cancer risk with an older age at first birth among HISP women was attenuated when adjusted for number of births and years since last birth (p trend = 0.76). The reduced risks associated with a higher number of births in both ethnic groups were essentially unchanged by adjustment for age at first birth and years since last birth. The proportion of HISP controls with more than two births was 0.567, whereas for non-Hispanic whites, the proportion was 0.449: The population attributable risks percents associated with higher numbers of births are estimated to be −12.7% for HISP and −8.3% for non-Hispanic whites, a 4.4% difference between the two ethnic groups.
Hispanic women who had ever breastfed had a somewhat reduced breast cancer risk compared to those who had given birth but had not breastfed, OR 0.87 (95% CI: 0.70, 1.09), but there was no evidence of a trend with duration of breastfeeding. There was a trend of inverse association between duration of breastfeeding and breast cancer among NHW women, which was attenuated when adjusted for number of births and age at first birth (p = 0.15). The trend with duration of breastfeeding was more evident among premenopausal non-Hispanic whites (), with an OR of 0.59 (95% CI: 0.37, 0.95) for 24 or more months of breastfeeding. Among premenopausal HISP women, the OR for the same duration of breastfeeding was 0.79 (95% CI: 0.46, 1.36).
The number of years that had elapsed between a last birth and the reference year were strong predictors of breast cancer risk among HISP women (p trend = 0.0003). HISP women who had given birth within five years had an approximate doubling of breast cancer risk relative to women with a 16–25 year interval since a birth (). When pre- and post-menopausal women were considered separately, the trend was present in each group, p = 0.004 and p = 0.01, respectively (). There was not a significant trend in breast cancer risk with years since a birth among NHW women (), although the comparison of women with more than 35 years since the last birth compared to women with 16–25 years since a birth, OR 0.71 (95% CI: 0.49, 1.02) indicated an almost-significantly reduced risk. There was evidence that there was a difference by ethnicity (p for interaction = 0.05) in the trend of reduced breast cancer risk with years since last birth.
There was no association between induced abortion and breast cancer in HISP or NHW women, nor was there an association in either ethnic group when the comparison was limited to premenopausal women.
We further examined associations between reproductive risk factors and subgroups of ER positive and ER negative breast cancers. Cases with missing ER status (32.5% of HISP cases and 32.4% of NHW cases) did not differ from those with known ER status on associations between reproductive variables and breast cancer risk (data not shown). Among HISP women, trends of lower breast cancer risk with age at menarche, higher risk with older age at first birth, reduced risk with higher parity, and reduced risk with years since last birth were all evident for estrogen receptor positive tumors (), but not for estrogen receptor negative tumors, with evidence of heterogeneity of effect for age at first birth (p = 0.001) and parity (p = 0.002). Among NHW women, there were qualitatively similar patterns in that older age at first birth or nulliparity increased the risk of ER positive, but not ER negative breast cancers, and the magnitude of reduced risk for more than two births was stronger for ER positive than for ER negative tumors. Heterogeneity of effects of parity or age at first birth by ER status was not statistically significant among non-Hispanic whites. Results were inconsistent for an association between breastfeeding and breast cancer, which was more evident for ER negative tumors among HISP but for ER positive tumors among non-Hispanic whites. Results were very similar if the subgroups were limited to cases with ER negative/progesterone receptor (PR) negative and ER positive/PR positive tumors (data not shown).
Reproductive history risk factors for breast cancer by estrogen receptor status of tumors, 4 Corners Study