Louis W.C. Chow

Breast Cancer in Limited-Resource Countries: An Overview of the Breast Health Global Initiative 2005 Guidelines

Abstract:  Breast cancer is the most common cause of cancer‐related death among women worldwide, with case fatality rates highest in low‐resource countries. Despite significant scientific advances in its management, most of the world faces resource constraints that limit the capacity to improve early detection, diagnosis, and treatment of the disease. The Breast Health Global Initiative (BHGI) strives to develop evidence‐based, economically feasible, and culturally appropriate guidelines that can be used in nations with limited health care resources to improve breast cancer outcomes. Using an evidence‐based consensus panel process, four BHGI expert panels addressed the areas of early detection and access to care, diagnosis and pathology, treatment and resource allocation, and health care systems and public policy as they relate to breast health care in limited‐resource settings. To update and expand on the BHGI Guidelines published in 2003, the 2005 BHGI panels outlined a stepwise, systematic approach to health care improvement using a tiered system of resource allotment into four levels—basic, limited, enhanced, and maximal—based on the contribution of each resource toward improving clinical outcomes. Early breast cancer detection improves outcome in a cost‐effective fashion assuming treatment is available, but requires public education to foster active patient participation in diagnosis and treatment. Clinical breast examination combined with diagnostic breast imaging (ultrasound ± diagnostic mammography) can facilitate cost‐effective tissue sampling techniques for cytologic or histologic diagnosis. Breast‐conserving treatment with partial mastectomy and radiation therapy requires more health care resources and infrastructure than mastectomy, but can be provided in a thoughtfully designed limited‐resource setting. The availability and administration of systemic therapies are critical to improving breast cancer survival. Estrogen receptor testing allows patient selection for hormonal treatments (tamoxifen, oophorectomy). Chemotherapy, which requires some allocation of resources and infrastructure, is needed to treat node‐positive, locally advanced breast cancers, which represent the most common clinical presentation of disease in low‐resource countries. When chemotherapy is not available, patients with locally advanced, hormone receptor‐negative cancers can only receive palliative therapy. Future research is needed to better determine how these guidelines can best be implemented in limited‐resource settings.

Challenges to effective cancer control in China, India, and Russia

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.

Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in cancer biology and treatment.

Thymidine phosphorylase (TP) is often induced in the tumour microenvironment by physiological and chemical stress. Its induction protects cells from apoptosis and helps cell survival by stimulating nucleoside metabolism and angiogenesis. Chemotherapy often upregulates TP, which acts in cell rescue; this result indicates that TP is a crucial therapeutic target. Clinical trials for metastatic diseases have shown that TP-targeting chemotherapy with fluorouracil derivatives greatly improves the effectiveness of conventional chemotherapy for not only response but also prognosis. This new idea, the improvement of TP-inducible therapy with TP-targeting therapy, should be further investigated for early disease states, and inhibitors of TP warrant extensive investigation.

Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer

Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well defined. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribution of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein truncation test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors.

Participation and Satisfaction with Surgical Treatment Decision-Making in Breast Cancer Among Chinese Women

AbstractPurpose. To report Chinese womens preferred and perceived participation in breast cancer treatment decision making (TDM), describe influences on womens participation preference and participation congruence (PC) (correspondence between preferred and actual amount of participation in TDM), and explore subsequent satisfaction with TDM. Patients and methods. Of 172/211 eligible and available Chinese women recently undergoing breast cancer surgery at one of six Hong Kong government hospitals 154 (89.5%) were recruited. Within 12 days after surgery, women provided interview information on preferred and perceived TDM participation, satisfaction with TDM consultation, difficulties in TDM, and medical and demographic information. Results. Half (55%) reported a treatment choice: 33% wanted the choice to be their own, 59% wanted to share and 8% wanted to delegate the decision. Only age predicted participation preference with older women preferring a more passive role. Eighty percent of women participated as much as, 13% more than and 6% less than desired. Adjusted for age, women reporting PC had fewer difficulties in TDM (β = 0.21, p = 0.009) than women not reporting PC, while over-involved women had more doubts about their choice (β = −0.23, p = 0.005). PC was associated with being offered a treatment option (χ2 = 15.59, p < 0.001) and surgeons expressing a surgical preference (χ2 = 6.63, p = 0.036). Satisfaction was unrelated to PC. Conclusion. Most Chinese women want shared TDM and to know their surgeons treatment preference. Over-involved women are at greater risk of difficulties and doubts in TDM and under-involved women perceive a lack of time and information to make their decision.

Her2/neu Expression Predicts the Response to Antiaromatase Neoadjuvant Therapy in Primary Breast Cancer: Subgroup Analysis from Celecoxib Antiaromatase Neoadjuvant Trial

Purpose: Many studies suggest that Her2/neu play an important role in neoadjuvant endocrine therapy. This study aimed to determine whether the level of Her2/neu expression in advanced breast cancer changes after antiaromatase neoadjuvant treatment, as well as to identify the relationship between Her2/neu expression and response to this kind of therapy. Experimental Design: Thirty-six postmenopausal patients with hormonal receptor-positive primary breast cancer were included in a study of three monthly cycles of neoadjuvant endocrine therapy with either Aromasin (25 mg daily) or Femara (2.5 mg daily). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for Her2/neu were conducted both on pretreatment biopsies and surgical tumors. Results: Using IHC, 5 of 36 (13.9%) of the patients had a Her2/neu overexpression after treatment, as compared with 16 of 36 (44.4%) before. Meanwhile, there was no change in 21 (58.3%) patients, and through FISH, there was a change from amplification to no amplification in 15 (41.7%) patients. The response rate to the treatment was 75% for Her2/neu (+) tumors and 35% for Her2/neu (−) tumors (P = 0.017) while FISH was performed. The response rate was also significantly affected by the decrease in Her2/neu status after the treatment, with 73% of the tumors showing decreased Her2/neu expression and with 38% of the tumors showing no change of Her2/neu expression (P = 0.037). Conclusions: Using both IHC and FISH, advanced breast cancers show statistical evidence of decreasing incidence of Her2/neu expression after antiaromatase neoadjuvant treatment. Our data also suggest that Her2/neu expression and its change during the treatment might be predictive markers for this kind of therapy.

Celecoxib anti-aromatase neoadjuvant (CAAN) trial for locally advanced breast cancer: preliminary report.

Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly in hormone-sensitive postmenopausal breast cancers. The initial results are reported. The patients were randomly assigned to receive exemestane 25 mg daily and celecoxib 400 mg twice daily (group A), exemestane 25 mg daily (group B) and letrozole 2.5 mg daily (group C). The analysis was based on 20 patients who received at least one cycle of treatment. Fourteen patients completed two cycles and 12 patients three cycles. All groups showed clinical response and there was decrease in tumor area in each group. However, complete clinical response was only observed for group A patients. There was also progressive decline in blood CEA and CA15.3 levels but the differences between the three groups were not significant. The results of the preliminary analysis are encouraging but definitive conclusion could only be drawn after the completion of the study.

Application of a nanotechnology antimicrobial spray to prevent lower urinary tract infection: a multicenter urology trial

BackgroundCatheter-associated urinary tract infection (CAUTI) is a common nosocomial device-associated infection. It is now recognized that the high infection rates were caused by the formation of biofilm on the surface of the catheters that decreases the susceptibility to antibiotics and results in anti-microbial resistance.In this study, we performed an in vitro test to explore the mechanism of biofilm formation and subsequently conducted a multi-center clinical trial to investigate the efficacy of CAUTI prevention with the application of JUC, a nanotechnology antimicrobial spray.MethodsSiliconized latex urinary catheters were cut into fragments and sterilized by autoclaving. The sterilized sample fragments were randomly divided into the therapy and control group, whereby they were sprayed with JUC and distilled water respectively and dried before use.The experimental standard strains of Escherichia coli (E. coli) were isolated from the urine samples of patients. At 16 hours and 7 days of incubation, the samples were extracted for confocal laser scanning microscopy.A total of 1,150 patients were accrued in the clinical study. Patients were randomized according to the order of surgical treatment. The odd array of patients was assigned as the therapy group (JUC), and the even array of patients was assigned as the control group (normal saline).ResultsAfter 16 hours of culture, bacterial biofilm formed on the surface of sample fragments from the control group. In the therapy group, no bacterial biofilm formation was observed on the sample fragments. No significant increase in bacterial colony count was observed in the therapy group after 7 days of incubation.On the 7th day of catheterization, urine samples were collected for bacterial culture before extubation. Significant difference was observed in the incidence of bacteriuria between the therapy group and control group (4.52% vs. 13.04%, p < 0.001).ConclusionsIn this study, the effectiveness of JUC in preventing CAUTI in a hospital setting was demonstrated in both in vitro and clinical studies.

Fine Needle Aspiration May Shed Breast Cells into Peripheral Blood as Determined by RT-PCR

Objective: A diagnostic test applying reverse-transcriptase chain reaction (RT-PCR) assay targeted against cytokeratin 19 (CK19), cytokeratin 20 (CK20) and the β-subunit of human chorionic gonadotropin (β-hCG) mRNAs was used to evaluate the impact of fine needle aspiration (FNA) on breast cell shedding into peripheral blood. Methods: The sensitivity of this assay was based on the different degree of admix of MCF-7 breast cancer cell line with HL-60 leukemic cell line. For blood samples of 24 cases with benign breast diseases and 20 cases with malignant ones, 5 ml of peripheral blood was drawn before and within 10 min after puncture. Total RNA was extracted from peripheral blood mononuclear (PBMN) cells; β-actin was used to assess the quality of cDNA. RT-PCR products were run in ethidium bromide gel and observed under ultraviolet. RT-PCR products for β-hCG were digested with Sty I endonuclease to confirm the specificity. Results: The sensitivity of RT-PCR assay was 1 MCF-7 cell in 105 HL-60 cells for CK19 and CK20, and 1 in 106 for β-hCG. For 24 benign cases, none of the pre- FNA samples was positive for CK20 and β-hCG, and 3 cases (12.5%) were positive for CK19. As for 20 malignant cases, 1 pre-FNA sample was positive for all three markers and 2 other samples were positive for CK19. After aspiration, 3/21 benign cases and 1/17 malignant case with pre-FNA negative signals became positive for CK19, while 3/19 malignant cases with pre-FNA negative signals were converted to a positive result for CK20 and β-hCG. Of 6 pre-FNA positive cases, all cases remained positive for the respective marker. Conclusion: FNA to breast tumor may cause hematogenous dissemination of breast cells.

Polysaccharide Peptide Mediates Apoptosis by Up-regulating p21 Gene and Down-regulating Cyclin D1 Gene

The use of herbal medicine is a common practice among Chinese women with breast cancer. Yunzhi (Voriolus versicolor), a substance that is regarded as a biological response modifier, is frequently used. The aim of the present study is to evaluate the anti-proliferative action of, Yunzhi, polysaccharide peptide (PSP), on breast cancer cells. Breast cancer cells (MDA-MB-231) were cultured with and without PSP for 7 days. Cell growth at 24, 72, 120 and 168 hours was measured by Cell Proliferation Reagent (WST-1). Cells treated with PSP were found to have a significant reduction in cell proliferation as compared to controls after 72 hours of incubation. This lasted for 168 hours. When the effect of PSP on apoptosis was studied by the TdT-mediated X-dUTP nick end-labeling (TUNEL) assay, we found that PSP had a significant effect upon apoptosis from 24 hours onward. Immunostaining showed that PSP increased p21 expression and decreased cyclin D1 expression. In conclusion, PSP is effective in inhibiting cell proliferation through apoptosis. The mechanism for the apoptosis may be through up-regulation of p21 and down-regulation of cyclin D1.