Effects of reproductive and demographic changes on breast cancer incidence in China: A modeling analysis

Background: Breast cancer incidence is currently low in China. However, the distribution of reproductive and lifestyle risk factors for breast cancer among Chinese women is changing rapidly. We quantified the expected effect of changes in breast cancer risk factors on future rates of breast cancer in China. Methods: We first validated and calibrated the Rosner-Colditz log-incidence breast cancer model in Chinese women who participated in the Shanghai Women's Health Study cohort (N = 74 942). We then applied the calibrated model to a representative sample of Chinese women who were aged 35-49 years in 2001 using data from the Chinese National Family Planning and Reproductive Health Survey (NFPRHS, N = 17 078) to predict the age-specific and cumulative breast cancer incidence among all Chinese women of this age group. We evaluated the relative impact of changes in modifiable risk factors, including alcohol intake, parity, postmenopausal hormone use, and adult weight gain, on cumulative incidence of breast cancer. Results: Breast cancer incidence in China is expected to increase substantially from current rates, estimated at 10-60 cases per 100 000 women, to more than 100 new cases per 100 000 women aged 55-69 years by 2021. We predicted 2.5 million cases of breast cancer by 2021 among Chinese women who were 35-49 years old in 2001. Modest reductions in hormone and alcohol use, and weight maintenance could prevent 270 000 of these cases. Conclusions: China is on the cusp of a breast cancer epidemic. Although some risk factors associated with economic development are largely unavoidable, the substantial predicted increase in new cases of breast cancer calls for urgent incorporation of this disease in future health care infrastructure planning

Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.

BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC

Breast cancer in Chinese media : privatization, cultural politics and subjectivity

University of Technology, Sydney. Faculty of Arts and Social Sciences.In the past three decades, China has experienced a profound social transformation, among which the retreat of government from the health care sector and the privatization of health issues is very significant. Chinese people are now required to make their own life choices and to be ‘self-responsible’ in all walks of lives, including their health. Against this general background, this thesis analyses the socio-cultural constructions of breast cancer in post-socialist China. This analysis works as a case study, through which I explore the complex intersection of the market, the government, health professionals and media in post-socialist China. Through textual analysis of media contents and semi-structured interviews, this thesis has uncovered the complex negotiations among various players in producing breast cancer related content. As a result of these negotiations, the prevention and treatment of the disease has been largely constructed as women’s own responsibilities and practices in the media. Since the government is providing less and less necessary financial and personnel support to conduct breast cancer public education, the breast cancer prevention campaign is often appropriated by international and domestic commercial forces alike to further their marketing interests. My analysis reveals two sets of relationships: between the privatization of the material goods and services and the privatization of the self, and between the political economic context of the health care reform and the cultural politics of the construction of breast cancer

Reproductive factors and incidence of breast cancer: An international ecological study

Summary: Ecological studies can help in understanding the relation of reproductive history to breast cancer. We analyzed data from 9416 women, comprising the control groups of seven countries (Australia, People's Republic of China, Colombia, (former) German Democratic Republic, Israel, Philippines, and Thailand) from the WHO international, multi-center case-control study of female cancers. Positive correlations with country-specific breast cancer incidence were observed for (median) duration of reproductive life (r≥0.95, p<0.005), age at menopause (r≥0.84, p<0.025) and delay to first birth (r≥0.59, p<0.22) (when People's Republic of China was omitted, r≥0.85, p<0.07). The association of age at first birth with breast cancer incidence was weakly positive in the whole sample (age-adjusted r=0.18, p=0.73), but weakly negative in the age groups 15-29 and 30-39 years and weakly positive in the age groups 40-49 and 50-64 years. A strong inverse correlation was observed between age at menarche and breast cancer incidence (r≤−0.84, p<0.03). These international ecological correlations agree with the associations previously reported for single populations, between higher incidence of breast cancer and younger age at menarche, older age at menopause, longer duration of reproductive life, and (possibly) longer delay to first birth. In contrast, age at first birth is only weakly related to breast cancer incidence across populations, indicating that this variable represents different constructs when measured ecologically versus individuall

NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.

N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this study, we investigated the regulation of NMI on CSCs traits in breast cancer and uncovered the underlying molecular mechanisms. We found that NMI was lowly expressed in breast cancer stem cells (BCSCs)-enriched populations. Knockdown of NMI promoted CSCs traits while its overexpression inhibited CSCs traits, including the expression of CSC-related markers, the number of CD44+CD24- cell populations and the ability of mammospheres formation. We also found that NMI-mediated regulation of BCSCs traits was at least partially realized through the modulation of hTERT signaling. NMI knockdown upregulated hTERT expression while its overexpression downregulated hTERT in breast cancer cells, and the changes in CSCs traits and cell invasion ability mediated by NMI were rescued by hTERT. The in vivo study also validated that NMI knockdown promoted breast cancer growth by upregulating hTERT signaling in a mouse model. Moreover, further analyses for the clinical samples demonstrated that NMI expression was negatively correlated with hTERT expression and the low NMI/high hTERT expression was associated with the worse status of clinical TNM stages in breast cancer patients. Furthermore, we demonstrated that the interaction of YY1 protein with NMI and its involvement in NMI-mediated transcriptional regulation of hTERT in breast cancer cells. Collectively, our results provide new insights into understanding the regulatory mechanism of CSCs and suggest that the NMI-YY1-hTERT signaling axis may be a potential therapeutic target for breast cancers

CD44ICD promotes breast cancer stemness via PFKFB4-mediated glucose metabolism.

CD44 is a single-pass cell surface glycoprotein that is distinguished as the first molecule used to identify cancer stem cells in solid tumors based on its expression. In this regard, the CD44high cell population demonstrates not only the ability to regenerate a heterogeneous tumor, but also the ability to self-regenerate when transplanted into immune-deficient mice. However, the exact role of CD44 in cancer stem cells remains unclear in part because CD44 exists in various isoforms due to alternative splicing. Methods: Gain- and loss-of-function methods in different models were used to investigate the effects of CD44 on breast cancer stemness. Cancer stemness was analyzed by detecting SOX2, OCT4 and NANOG expression, ALDH activity, side population (SP) and sphere formation. Glucose consumption, lactate secretion and reactive oxygen species (ROS) levels were detected to assess glycolysis. Western blot, immunohistochemical staining, ELISA and TCGA dataset analysis were performed to determine the association of CD44ICD and PFKFB4 with clinical cases. A PFKFB4 inhibitor, 5MPN, was used in a xenograft model to inhibit breast cancer development. Results: In this report, we found that the shortest CD44 isoform (CD44s) inhibits breast cancer stemness, whereas the cleaved product of CD44 (CD44ICD) promotes breast cancer stemness. Furthermore, CD44ICD interacts with CREB and binds to the promoter region of PFKFB4, thereby regulating PFKFB4 transcription and expression. The resultant PFKFB4 expression facilitates the glycolysis pathway (vis-à-vis oxidative phosphorylation) and promotes stemness of breast cancer. In addition, we found that CD44ICD and PFKFB4 expressions are generally up-regulated in the tumor portion of breast cancer patient samples. Most importantly, we found that 5MPN (a selective inhibitor of PFKFB4) suppresses CD44ICD-induced tumor development. Conclusion: CD44ICD promotes breast cancer stemness via PFKFB4-mediated glycolysis, and therapies that target PFKFB4 (e.g., 5MPN therapy) may lead to improved outcomes for cancer patients

All Sites but Skin Cancer Incidences Analyzed Worldwide by Sex, Age, and Skin Type Over Time (1955-2007), Advancing Age, and UVB Dose Reveals Important Carcinogenic Drivers

Because we observed increasing incidences over time, advancing age, higher estrogen levels, decreasing UVB (290-315 nm) doses, or lower vitamin D3, and Human Papillomavirus hiding in immune-privileged sites of hair follicles play roles in melanoma, we wondered if the majority of cancers might have similar carcinogenic drivers. To investigate this possibility, we performed worldwide analysis of all sites but skin cancer over time (1955-2007), advancing age, and UVB doses for males and females with all skin types and ages (0-85+) and in five age groups using IARC data. To investigate Human Papillomavirus’s role, we analyzed the incidences of breast, prostate, and colon cancers in a developed country with European ancestry (New Zealand) having high amounts of androgenic hair and a developing country with Asian ancestry (India) having low amounts of androgenic hair. To potentially add epidemiology to the already established role of estrogen in cancer, we analyzed males and females in various countries around the world using the incidence of breast cancer (\u3e 70 yr.) as an established indicator of estrogen levels. The analysis reveals cancer incidences are steadily increasing over time in developed but not developing countries regardless of skin type. Only US white, but not black, breast, prostate, and colon cancer incidences in the oldest age group significantly decreased with increasing UVB dose suggesting a role for vitamin D3. The data suggests the carcinogenic drivers in many cancers are estrogen, increasing age (or reactive oxygen species), decreasing vitamin D3 levels, and persistence of Human Papillomavirus infection in immune-privileged sites

Gus Lee

Augustus Samuel Mein-Sun Lee was born in San Francisco on August 8, 1946, the only son of Tsung-Chi Lee and Da-Tsien Tsu. His three sisters had been born in mainland China and accompanied his mother on the difficult trek across China to India and then to the United States in 1944. There, the family rejoined Tsung-Cbi, wbo had once been a major in the Kuomintang army and who, since 1939, had been working in San Francisco for the Bank of Canton. When Gus was only five, his mother died of breast cancer, and his father, two years later, married a severe Pennsylvania Dutch woman. Gus grew up in the Panhandle and the Haight, a predominantly African American area of San Francisco, and he had a difficult time becoming accepted. He joined the Young Men\u27s Christian Association (YMCA) and learned to box