Rapidly Emerging Young Female Breast Cancer in Taiwan: Study on Clinicopathology and Tumor Biology
Date Issued
2011
Date
2011
Author(s)
Lin, Ching-Hung
Abstract
Although the incidence of invasive breast cancer in women is lower in Asian countries than in Western countries, it has been rapidly increasing in parts of Asia, including Singapore, Korea, Japan, and Taiwan. Similar to findings in Japan, the previous showed a significantly stronger birth cohort effect on the incidence trend of breast cancer in Taiwanese than in Caucasian Americans. This strong birth cohort effect suggests that a change in environmental exposure might have had a great impact on the pathogenesis of breast cancer in these countries.
The most widely cited environmental factor responsible for increasing the incidence of breast cancer in developing countries is the Westernized lifestyle. However, evidence for this hypothesis remained to be explored. A reasonable first step to test this hypothesis is to compare the molecular subtypes between the two populations.
Our first study included 1028 breast cancer diagnosed between 2004 and 2006. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), cytokeratin 5/6, and epidermal growth factor receptor expressions were used to define the molecular subtypes. Our result showed that younger (≤50 years) breast cancer patients had a higher prevalence of luminal A and a lower prevalence of basal-like subtype compared with older (>50 years) patients. The frequency of luminal A subtype was even more prevalent in younger (≤50 years) Taiwanese patients (66%) than premenopausal African Americans (36%) and non-African Americans (51%). Furthermore, the basal-like breast cancer was less prevalent in younger Taiwanese (9%) than in premenopausal African Americans (39%) and non-African Americans (16%). We conclude that young breast cancer patients in Taiwan are characterized by a high prevalence of luminal A subtype, and low prevalence basal-like subtype. These features are distinct from young breast cancer patients in Western countries and suggest that westernized lifestyle may not be the only reason for the rapid increasing breast cancer in young Taiwanese women.
Our second study analyzed the age-spcific trends of histopathological subtypes of female breast and three major genital tract cancers (cervical, uterine and ovarian cancers) in Taiwane. We used a descriptive epidemiological method and data from the Taiwan Cancer Registry (1979- 2007) to examine secular trends in their age-specific incidences and histopathological subtypes. During the period of 1998–2007 in Taiwan, the incidence of breast and uterine cancers was found to increase to a much greater extent than that of the reference controls. The greatest increases in breast and uterine cancer rates occurred in young Taiwanese women. Uniquely bell-shaped age-specific incidence curves were observed which differed significantly from those for Caucasian American women.
The main subtypes significantly increasing in incidence were: for women aged ≤55 years, ductal carcinoma and lobular carcinoma (breast cancer), endometrioid adenocarcinoma (uterine cancer), and endometrioid carcinoma (ovarian cancer); for women aged >60 years, serous and clear cell adenocarcinomas (uterine cancer). The endometrioid carcinoma of uterine (type I endometrial cancer) is an estrogen dependent tumor. In contrast, type II endometrial cancer including serous and clear cell carcinomas is estrogen unrelated. For breast cancers, we analyzed the data obtained from the TCDB in 2005–2006 (n = 12,436) and found that both ER+ and PR+ rates were uniquely higher in younger, as compared to older, Taiwanese women. These findings provide strong support for a rapid increase in the incidence of estrogen-related malignancies in young women in Taiwan.
Our third study analyzed the prognostic factors in 116 very young breast cancer in Taiwan. The result showed that high Ki67 expression, HER2 overexpression, and TP53 mutations were independent predictors of poor prognosis in women aged ≤35 years with breast cancer. ER expression was associated with longer overall survival in the univariate analysis but not in the multivariate analysis. PR and PIK3CA mutations were not associated with survival in this population. Further studies are mandatory to answer whether there is ethnic difference in this population.
Etiologies of young female breast cancer in Taiwan may involve excess estrogen from either endogenous or exogenous sources. Beyond endogenous estrogens, certain industrial environmental pollutants with estrogenic effects may also be causative and deserve further investigation. For example, the urinary concentration of plasticizer- Bis(2-ethylhexyl)- phthalate (DEHP) in Taiwanese was extraordinarily high. In May 2011, it was disclosed that hundreds of food ingredients were contaminated by the DEHP in Taiwan. The investigation on this case suggests that DEHP contamination in Taiwan had existed for more than two decades. In the plasticizer highly polluted areas such as Taiwan and parts of Asia, the association of these plasticizer exposure and emerging young female breast deserves the priority of investigation.
In addition, genetic components, particularly those genes involving estrogen synthesis or metabolism, may also play a role. Determining the responsible environmental factors or gene-environment interactions leading to carcinogenesis in younger women with estrogen-related malignancies in Taiwan and other rapidly developing countries in Asia represents a challenging and important objective.
Subjects
Taiwan
young female
breast cancer
molecular subtype
estrogen
prognostic factor
SDGs
Type
thesis
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