Heterogeneity of epidemiological factors by breast tumor subtypes in Korean women: A case-case study

Abstract

Breast cancer is heterogeneous in clinical behavior by subtypes; however, it is unclear how this heterogeneity is related to epidemiological factors. To evaluate the differences in epidemiological factors by breast tumor subtypes, we investigated the associations of epidemiological factors between tumor subtypes in Korean women. From the Seoul Breast Cancer Study, a total of 3,058 patients with breast cancer were included in the analyses. Tumor subtypes were classified based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses. The epidemiological factors of each subtype were compared through case-case analyses using multivariate a polytomous logistic regression model adjusted for age and recruiting centers. The distribution of the subtypes was as follows: 1,714 HR1 HER22 (56.0%), 414 HR1 HER21 (13.5%), 423 HR2 HER21 (13.9%) and 507 HR2 HER22 (16.6%) patients with breast cancer. There were significant differences in age, menopausal status, age at menarche, number of children, age at first full-term pregnancy (FFTP), duration of breastfeeding and duration of endogenous estrogen exposure between tumor subtypes (p < 0.05). Compared to HR1 HER22 patients, the other subtype patients showed more frequency in having more numbers of children and less frequency in having earlier menarche, later FFTP and longer endogenous estrogen exposure. Although HR2 HER21 patients were less obese, HR2 HER22 patients were younger and more obese. In conclusion, age, body mass index and reproductive factors were differentially associated with breast tumor subtypes suggesting a possible distinct etiology for tumor progression.Breast cancer is a heterogeneous disease in terms of clinical behavior. Breast tumors have been classified into intrinsic subtypes using gene expression patterns measured by microarrays.1-3 The intrinsic subtypes were explained as the clinicopathological definition based on the expression of estrogen and progesterone receptors (ER and PR), human epidermal growth factor receptor 2 (HER2) and For the basallike subtype of breast cancer, epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) were also used as surrogates.5 These tumor subtypes have shown significant differences in their clinical features. 2,3,6 Notwithstanding the clinical heterogeneity of the tumor subtype, the etiological heterogeneity has not been established.7 Through previous epidemiological studies, several reproductive factors, such as early menarche, late menopause and late age at first full-term pregnancy (FFTP), and family history have been established as risk factors of breast cancer, and obesity has been probable as protective or a risk factor of breast cancer depending on the menopausal status. [8][9][10] Furthermore, well-known risk factors of breast cancer have been associated with the ER-positive subtype rather than the ER-negative subtype.

A Review of the Epidemiology of Breast Cancer in Asia: Focus on Risk Factors

“…Early menarche (before age 12 years) and late menopause (after age 55 years) are associated with increased risk of BC, likely due to a longer lifetime exposure to estrogen and progesterone (American Cancer Society, 2016). Several studies demonstrated a link between menopausal status and BC risk and was seen across participants from Thailand (Anothaisintawee et al, 2014), India (Chattopadhyay et al, 2014), Pakistan (Song et al, 2014a), and Korea (Park et al, 2013). As expected, the studies showed an increased BC risk in women who had a lower age of menarche (Bhadoria et al, 2013;Chung et al, 2013) and a later age of menopause (Bhadoria et al, 2013;Shamsi et al, 2013;.…”

“…A study conducted in Malaysia found that the majority of BC cases were hormone receptor-negative (Horne et al, 2015). Conversely in a Korean study, 69.5% of BCs were hormone receptor-positive (Song et al, 2014a) and 44.6% of BCs were estrogen receptor-positive in an Indian study (Singh et al, 2014). Among participants from Korea, when estrogen receptor-positive/progesterone receptor-positive tumors were compared to estrogen receptor-positive/progesterone receptor-negative tumors, women with the latter were 4 years older at diagnosis and more likely to be postmenopausal (Chung et al, 2013).…”

Tumor Subtype-Specific Associations of Hormone-Related Reproductive Factors on Breast Cancer Survival

“…This is a follow-up study that included eligible patients previously enrolled in the Seoul Breast Cancer Study (SEBCS), a multicenter-based case-control study on breast cancer described elsewhere[ 32 , 33 ]. The patients with histologically confirmed incident breast cancer at department of surgery of Seoul National University Hospital (SNUH) or ASAN Medical Center (AMC) were recruited and enrolled in the SEBCS between 2001 and 2007.…”

“…The duration of lifetime endogenous estrogen exposure was calculated by subtracting the age at menarche from the age at diagnosis for premenopausal women and from the age at menopause for postmenopausal women. The duration of endogenous estrogen exposure before FFTP was defined as the period between menarche and FFTP for parous women and the period between menarche and diagnosis or menopause for pre- and postmenopausal nulliparous women, respectively, as previously described[ 33 ]. The reference groups were defined as the first category of each variable and the greater proportion in each variable including age and BMI for the statistical stability.…”

Prediction of Breast Cancer Survival Using Clinical and Genetic Markers by Tumor Subtypes

“…The Seoul Breast Cancer Study (SEBCS) is a multicenter-based case-control study of female breast cancer in Seoul, Korea as previously reported[ 29 , 30 ]. This two-stage GWAS included a total of 3,226 incident breast cancer cases.…”