Reproductive factors and breast cancer risk in relation to hormone receptor and menopausal status in Japanese women

Abstract

The associations between menstrual and reproductive factors and breast cancer risk in relation to estrogen/progesterone receptor (ER/PgR) status have been unclear in Japanese women. This case-control study evaluated these associations, overall and separately, by menopausal status. A total of 1092 breast cancer cases and 3160 controls were selected from among female patients aged 30 years and over admitted to a single hospital in Miyagi Prefecture between 1997 and 2009. The receptor status distribution among the cases (missing: 8.4%) was 571 ER+/PgR+, 133 ER +/PgRÀ, 24 ERÀ/PgR+ and 271 ERÀ/PgRÀ. Menstrual and reproductive factors were assessed using a self-administered questionnaire. Polytomous logistic regression and tests for heterogeneity across ER+/PgR+ and ERÀ/PgRÀ were conducted. Later age at menarche was significantly associated with a decreased risk of both ER+/PgR+ and ERÀ/PgRÀ cancer among women overall (P trend = 0.0016 for ER+/PgR+; P trend = 0.015 for ERÀ/PgRÀ) and among postmenopausal women (P trend = 0.012 for ER+/PgR+; P trend = 0.0056 for ERÀ/PgRÀ). Nulliparity was associated with an increased risk of ER+/PgR+, but not ERÀ/PgRÀ cancer among women overall (P heterogeneity = 0.019) and among postmenopausal women (odds ratio for ER+/PgR+ = 2.56, 95% confidence interval = 1.61-4.07; P heterogeneity = 0.0095). A longer duration of breastfeeding tended to be associated with a decreased risk in all subtypes among women overall. Later age at menarche has a protective effect against both ER+/PgR+ and ERÀ/PgRÀ cancer. However, parity might impact differently on various subtypes of breast cancer. Further studies are needed to clarify the etiology of the rare ER+/PgRÀ and ERÀ/PgR+ cancer subtypes. (Cancer Sci 2012; 103: 1861-1870 O ver the past few decades, numerous epidemiologic studies of breast cancer have been conducted, based mainly on Caucasian populations. These studies show that menstrual and reproductive factors and menopausal status are associated with breast cancer risk.(1,2) In Japan, cohort studies, (3,4) casecontrol studies (5)(6)(7) and a meta-analysis have revealed similar associations. (8) Breast cancers are known to express the estrogen receptor (ER) or progesterone receptor (PgR). Tumor subtypes defined by these receptors represent biologically different entities.(9) In Western countries, many studies have evaluated breast cancer risk according to hormone receptor status.(10-13) A meta-analysis shows that nulliparity is associated with a higher risk of ER+ tumors, but not ERÀ tumors.(13) Another meta-analysis suggests that nulliparity is associated with an increased risk of ER+/PgR+ tumors, but not ERÀ/PgRÀ tumors. The protective effects of late age at menarche and longer duration of breastfeeding do not differ across ER/PgR status. (12) Among studies conducted in the Asian region, a large-scale case-control study from China evaluates risk factors defined according to the four types of hormone receptor status and finds an association with parity history similar to that in the abovemention...

BMI, reproductive factors, and breast cancer molecular subtypes: A case-control study and meta-analysis

“…Previous studies have observed a negative relationship between parity and breast cancer 18, 31, 45, 46, 47. In our case-control study, the number of nulliparous women was small, especially in the sets of molecular subtypes.…”

“…Of the remaining 12 studies, the risk factors in Yoo's, 24 Suzuki's, 25 and Tamaki's 26 studies from Japan, Chung's study from Korea, 27 and Adam's study from China 28 lacked frequencies, and one study including subjects from Vietnam and China reported the molecular subtypes according to single ER status, PR status, or HER2 status 29 . Among the remaining six studies,18, 19, 30, 31, 32, 33 two studies from Japan were performed on an overlapping population. In considering whether it was feasible to pool the data, we used the frequencies of BMI from Sueta et al 33 and that of reproductive factors reported by Islam 30 to calculate pooled effects separately.…”

Reproductive and hormonal factors, family history, and breast cancer according to the hormonal receptor status

“…In particular, in a meta-analysis, the relative risk (RR) for late menarche was 0.7 in ER + PR + and 0.8 in ER -PRbreast cancers (Ma et al, 2006). However, several studies published after this meta-analysis did not find any difference for age at menarche across the hormonal receptor status (Rosenberg et al, 2006;Chlebowski et al, 2007;Iwasaki et al, 2007;Li et al, 2007;Menes et al, 2007;Li et al, 2008;Dey et al, 2009;Bao et al, 2011;Collaborative Group on Hormonal Factors in Breast Cancer, 2012;Kawai et al, 2012;Ritte et al, 2012). In particular, a pooled analysis of 117 studies including 27 245 breast cancer cases reported a RR of 1.1 for every 1 year decrease in the age at onset of menarche for both ER -and ER + cancers (Collaborative Group on Hormonal Factors in Breast Cancer, 2012).…”

Alcohol Consumption and Breast Cancer Risk According to Hormone Receptor Status in Japanese Women: A Case-Control Study

“…The difference in the risk of ER+/PgR− cancer among regions and races suggests that alcohol-related breast cancer risk may reflect not only the direct biologic effects of alcohol but also the distributions of other risk factors and sociocultural background. For example, our previous case-control study showed that the associations of established breast cancer risk factors including reproductive and anthropometric factors with the risk of ER+/PgR− cancer were weak or unity, suggesting that the epidemiologic characteristics of ER+/PgR− cancer may differ from those of other receptor subtypes (Kawai et al 2012(Kawai et al , 2013. The characteristics of cases and controls shown in Table 1 also suggest such a difference.…”

“…The procedure used in this survey has already been described previously (Minami and Tateno 2003;Fujita et al 2008;Kawai et al 2012Kawai et al , 2013Nishino et al 2014). The purpose of the survey was explained on the cover page of the questionnaire.…”