Assessment of menopause-related symptoms in mid-aged women with the 10-item Cervantes Scale

Objective

To develop a short 10 item version of the original menopause Cervantes Scale (CS) in order to assess menopausal symptoms in a large cohort of mid-aged Colombian women.

Methods

Reliability of the new short tool was assessed through internal consistency determination (Cronbach's alpha values) and intra-class correlation coefficient (ICC) analysis. Ten items out of the 31 composing the original CS were selected according to their clinical relation with menopausal symptoms. Subsequently the short tool was used to assess menopausal symptoms and related factors among 1739 mid-aged women.

Results

The CS-10 displayed a mean (±SD) ICC value of 0.45 (±0.06) and a Cronbach's alpha of 0.778 suggesting good internal reliability. For the entire sample median [interquartile range] CS-10 global scores were 10.0 [12.0], and for pre-, peri- and postmenopausal women: 8.0 [9.2], 9.0 [9.0] and 14.0 [14.0], respectively. Median global CS-10 scores significantly increased with menopausal status, marital status and ethnicity. Multiple linear regression analysis determined that higher global CS-10 scores (worse quality of life) correlated with age, parity, years since menopause, body mass index, ethnics (black) and smoking habit.

Conclusion

The CS-10 seems to be a simple instrument that may aid everyday clinical consultation and help at performing an accurate diagnosis of menopause-related symptoms. Further studies are needed to confirm our preliminary findings.     

Association of race and breast cancer stage

PURPOSE: To determine if breast cancer stage exhibits any significant variation between African Americans and white Americans. METHODS: We conducted a retrospective cohort study. Inclusion criteria required a diagnosis of breast cancer that was reported to the TriHealth tumor registry from 1991-2003. For each patient, we collected data on race; American Joint Committee on Cancer stage at diagnosis; and 12 potential confounding variables, including topography, morphology, laterality, age, menopausal age, smoking status, estrogen and progesterone receptor status, marital status, menopausal status, family history of breast cancer in a first-degree relative and insurance status. RESULTS: 5,751 patients (5,119 Caucasians, 632 African Americans) were eligible to be included in the study. African Americans were significantly younger, with a younger age of menopause, less family history of breast cancer, fewer positive estrogen and progesterone receptors, higher rate of cigarette smokers, more Medicaid insured, and more single and divorced individuals compared to Caucasian Americans (p < 0.05). Multivariate analysis found no difference between the races for stage 0, stage 2 and stage 4. African Americans had significantly less stage 1 (RR 0.80, 95% CI: 0.67-0.96), less combined stage 0 and 1 (RR 0.75, 95% CI: 0.63-0.89) and more combined stage 3 (RR 1.50 95% CI: 1.11-2.01). CONCLUSION: Although there was no difference among the races for topography, morphology and laterality of their breast cancers, African-American race is a predictor of more advanced stage at diagnosis.     

Improving quality of life after breast cancer: dealing with symptoms

BackgroundAdvances in breast cancer therapies have given rise to a growing number of patient survivors. Nevertheless, these women deal with long-term sequelae that impair their quality of life and that are lacking satisfactory assessment and expeditious management. Importantly, a new era is raising in the oncology field, namely, survivorship.MethodsA search for English-language articles on Medline was undertaken covering the last 15 years, using the terms “cancer survivorship”, “quality of life”, “fatigue”, “insomnia”, “sleep disturbances”, “depression”, “cognitive dysfunction”, “chemofog”, “peripheral neuropathy”, “fertility”, “sexual behaviour”, “menopause”, “lymphedema”, “physical activity” and “breast neoplasms”. Selection was limited to systematic reviews and meta-analysis, but their reference list was examined to include papers of potential interest.ResultsWe found the most common symptoms affecting breast cancer survivors were fatigue, insomnia, depression, cognitive dysfunction, reproductive and menopausal symptoms and lymphoedema.ConclusionSome of these symptoms have even been the objective of randomised controlled trials, but consistent data are missing. The available interventions include pharmacological, behavioural therapies and complementary and alternative medicine approaches and will mostly depend on the type of symptom.     

瘦素受体在乳腺癌中的表达及其与乳腺癌相关基因的相关性分析

Objective To study the expression levels of leptin receptor（LEPR） in breast cancer cell lines, normal breast samples and malignant breast cancer samples, and to analyze the expression correlation between LEPR and estrogen receptor（ER）, E-cadherin（E-Cad）, c-Myc and cyclin D1 in order to provide mechanism clues for obesiety associated breast cancer. Methods Using RT-PCR and Western blotting, we examined the expression of LEPR in different breast cancer cell lines. The expression level of LEPR was analyzed by RT-PCR in 5 paired breast samples. In the meanwhile, The expression of LEPR, ER, E-Cad, c-Myc and cyclin D1 was analyzed using realtime PCR in 45 breast cancer samples and 15 normal breast samples. The correlation was analyzed between the expression of LEPR and the expression of ER, E-Cad, c-Myc and cyclin D1 using SPSS statistic software. Results LEPR mRNA and protein were expressed in all breast cancer cell lines tested in this study. The expression of LEPR in the breast cancer samples was higher than in the paired adjacent normal breast tissues. With the statistic analysis, the expression of LEPR was correlated with expression of ER in both normal and malignant breast samples. LEPR expression was also close correlated with E-Cad and c-Myc expression in the breast cancer samples, but not with cyclin D1 expression. Conclusion LEPR expresses in breast cancer cell lines. Compared to the normal breast tissues, the expression of LEPR in breast c     

Hormone replacement therapy and breast cancer

Numerous studies on oestrogen replacement therapy have failed to incriminate the use of exogenous oestrogen as a cause of breast cancer in post-menopausal women. Since so many variables influence breast cancer risk, it has not been possible for any single study to evaluate every potential risk factor included in the epidemiological and clinical reports on hormone use and carcinoma of the breast. The relative risk (RR) for breast cancer in oestrogen users has been found to vary from 0.4 to 3.4, with the vast majority of investigators reporting an RR very close to 1.0, or no increased risk at all. There is growing evidence that progesterone deficiency may increase the risk for breast cancer in some women. At least three studies have indicated that the addition of progestogen to oestrogen replacement therapy may significantly decrease the risk for carcinoma of the breast. It was observed that the RR of breast cancer varied from 0.47 to 0.89 in these studies when oestrogen-progestogen users were compared with unopposed oestrogen users. However, it is pointed out that progestogens are not added to oestrogen replacement therapy to negate an increased risk of breast cancer from unopposed oestrogens, since oestrogen therapy does not increase the risk. Combination oestrogen-progestogen therapy is recommended for hormone replacement treatment, even in women who have had a hysterectomy, because it will reduce the risk for breast cancer in some women.     

Management of menopausal symptoms in breast cancer patients

In breast cancer patients, menopausal symptoms such as hot flashes, urogenital problems, musculoskeletal symptoms and cognitive dysfunction are common, regardless of age at diagnosis. They affect quality of life and systemic therapy will worsen this. Endocrine and/or chemotherapy may induce temporary or permanent ovarian failure and can exacerbate these symptoms. Hormone therapy (HT) has been studied in breast cancer survivors, but safety has been questioned. The HABITS trial investigating estrogen-based HT, as well as the LIBERATE trial investigating tibolone, found a reduction in disease-free survival for those treated. Alternative strategies are needed, as menopause symptoms may reduce compliance with breast cancer treatments. This article reviews recently published strategies to tackle menopausal problems in breast cancer patients. Antidepressants may help with hot flashes. Acupuncture and hypnosis can also be used but the evidence is conflicting. For urogenital problems vaginal moisturizers or topical estrogens can be employed. A musculoskeletal syndrome induced by aromatase inhibitors (AIs) is frequently encountered and currently there are no effective treatment strategies. Bisphosphonates reduce AI-induced bone resorption and can also increase disease-free and overall survival. Standard-dose endocrine and chemotherapy are associated with a decline in cognitive function.     

Association of FABP5 expression with poor survival in triple-negative breast cancer: implication for retinoic acid therapy

Recent studies using animal models suggest that expression of FABP5 drives the stimulation of cell growth observed in estrogen receptor (ER)-negative breast cancer cells on exposure to retinoic acid (RA). The purpose of this study was to investigate the clinicopathological significance of FABP5 in breast cancer and to evaluate FABP5 as a prognostic marker and a possible novel therapeutic target in breast cancer. Gene expression microarray analysis revealed a significant correlation between elevated FABP5 RNA levels and ER/progesterone receptor (PR)-negative status, high tumor grade, and poor prognosis. Tissue microarray analysis demonstrated similar correlations with cytoplasmic FABP5 protein. Based on multivariate proportional regression analysis, cytoplasmic FABP5 is a significant and independent prognostic marker of overall survival and recurrence-free survival in breast cancer. The effects of FABP5 on tumor growth appear to be mediated primarily through cytoplasmic FABP, because no correlation was found between nuclear FABP5 and ER/PR-negative status, recurrence, and survival. FABP5 knockdown in breast cancer cell lines demonstrates a correlation between FABP5 levels and growth response to RA. We propose a model whereby growth-promoting FABP5 competes with growth-inhibiting CRABP2 for RA, with retention of RA in the cytoplasm by FABP5 preventing the inhibition of tumor growth.     

乳腺癌患者的心身症状与生活质量

目的:探讨乳腺癌患者抑郁、焦虑的心理症状与躯体症状之间的关系,心身症状与生活质量的关系以及心身症状和生活质量与患者所接受过的治疗和生存期的关系.方法:本研究采用横断面设计,对北京市315例符合入组标准的乳腺癌患者进行调查,所使用的调查工具包括病人健康问卷(PHQ-15)、病人健康问卷抑郁量表(PHQ-9)、广泛性焦虑量表(GAD-7)及癌症患者生命质量测定量表(QLQ-C30),并对255份有效数据进行了分析.结果:乳腺癌患者躯体症状的严重程度与抑郁、焦虑均呈正相关(r=0.44,0.56;均P＜0.01);在重度躯体症状的患者中,抑郁的发生率为42.3％,焦虑的发生率为50％;抑郁、焦虑与乳腺癌患者总体健康状况相关(β=-0.22,-0.30;均P＜0.01);接受化疗的患者其躯体症状和抑郁、焦虑得分高于未接受化疗的患者[(9.0±5.0)vs.(6.0±4.1),(8.3±6.0) vs.(4.0±3.5),(5.4±5.0)vs.(3.1±3.7);均P＜0.01];生存期5年以上的乳腺癌患者只有焦虑分数低于5年以内的患者[(5.8±5.0)vs.(4.3±4.5),P＜0.05],在躯体症状、抑郁和生活质量方面差异无统计学意义.结论:乳腺癌患者抑郁、焦虑的心理症状与其躯体症状和总体健康状况相关,接受化疗患者的心身症状和生活质量可能会更差一些,生存期5年以上的患者焦虑水平低于5年以内的患者,但躯体症状、抑郁以及生活质量与生存期的延长未见相关.     

Nanotechnology for breast cancer therapy

Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact. Clinical trials currently employing these drugs in combination with chemo and biological therapeutics exceed 150 worldwide. Despite these advancements, breast cancer morbidity and mortality is unacceptably high. Nanotechnology offers potential solutions to the historical challenge that has rendered breast cancer so difficult to contain and eradicate: the extreme biological diversity of the disease presentation in the patient population and in the evolutionary changes of any individual disease, the multiple pathways that drive disease progression, the onset of ‘resistance’ to established therapeutic cocktails, and the gravity of the side effects to treatment, which result from generally very poor distribution of the injected therapeutic agents in the body. A fundamental requirement for success in the development of new therapeutic strategies is that breast cancer specialists—in the clinic, the pharmaceutical and the basic biological laboratory—and nanotechnologists—engineers, physicists, chemists and mathematicians—optimize their ability to work in close collaboration. This further requires a mutual openness across cultural and language barriers, academic reward systems, and many other ‘environmental’ divides. This paper is respectfully submitted to the community to help foster the mutual interactions of the breast cancer world with micro- and nano-technology, and in particular to encourage the latter community to direct ever increasing attention to breast cancer, where an extraordinary beneficial impact may result. The paper initiates with an introductory overview of breast cancer, its current treatment modalities, and the current role of nanotechnology in the clinic. Our perspectives are then presented on what the greatest opportunities for nanotechnology are; this follows from an analysis of the role of biological barriers that adversely determine the biological distribution of intravascularly injected therapeutic agents. Different generations of nanotechnology tools for drug delivery are reviewed, and our current strategy for addressing the sequential bio-barriers is also presented, and is accompanied by an encouragement to the community to develop even more effective ones.     

乳腺癌治疗靶点及靶向治疗研究新进展

乳腺癌靶向治疗在临床实践中取得了显著的疗效,把乳腺癌的治疗推向了一个前所未有的水平。信号转导干预治疗是针对信号转导通路中发生异常的环节来干预这种不正常的信号转导,从而达到抑制肿瘤生长的目的,主要治疗药物有曲妥珠单抗、拉帕替尼、蛋白激酶C（PKC）-α抑制剂、环氧化酶2（COX-2）抑制剂。表皮生长因子受体（EGFR）靶向治疗的主要药物有吉非替尼和西妥昔单抗,其它的靶点和药物有血管内皮生长因子（VEGF）的靶向治疗（贝伐单抗）、血管生成抑制（阿瓦斯丁）、细胞凋亡（G3139和组蛋白脱乙酰基转移酶抑制剂）和热点靶蛋白（Mr70000）。本文主要讲述了乳腺癌治疗的靶点及靶向治疗研究新进展。乳腺癌分子靶向治疗的优势很多,但还不能替代传统的手术切除和化疗,靶向治疗只是术后辅助治疗的一种重要的手段。     

Cognitive changes associated with endocrine therapy for breast cancer

Endocrine therapy in the setting of breast cancer has undoubtedly advanced clinical outcomes in this disease, but treatment with endocrine therapy is accompanied by a wide spectrum of side effects. It is of prime importance to understand and characterize these toxicities to facilitate clinical decision-making. Somewhat surprisingly, there is a relative paucity of data pertaining to cognitive changes associated with endocrine therapy. In this article we review cognitive associated with two classes of endocrine therapy: (1) selective estrogen receptor modulators (SERMs; tamoxifen and raloxifene) and (2) aromatase inhibitors (AIs; anastrozole, letrozole, and exemestane). Companion studies to the Multiple Outcome of Raloxifene Evaluation (MORE), the Study of Tamoxifen and Raloxifene (STAR) and National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trials provide relevant data to understand the effect of SERMs on cognition. In contrast, substudies of the Arimidex, Tamoxifen Alone or in Combination (ATAC), Tamoxifen and Exemestane Adjuvant Multinational (TEAM) and Breast International Group (BIG) 1-98 trials juxtapose cognitive effects of AIs against those of tamoxifen. These and other studies are examined herein to provide a comprehensive overview of the effect of endocrine therapy on cognition.     

Postmenopausal testosterone therapy and breast cancer risk

Background: Testosterone therapy is being increasingly used in the management of postmenopausal women. However, as clinical trials have demonstrated a significantly increased risk of breast cancer with oral combined estrogen–progestin therapy, there is a need to ascertain the risk of including testosterone in such regimens. Objective: Evaluation of experimental and epidemiological studies pertaining to the role of testosterone in breast cancer. Design: Literature review. Setting: The Jean Hailes Foundation, Research Unit. Main Outcome Measures: Mammary epithelial proliferation, apoptosis and breast cancer. Results: In experimental studies, testosterone action is anti-proliferative and pro-apoptotic, and mediated via the AR, despite the potential for testosterone to be aromatized to estrogen. Animal studies suggest that testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer promoting effects of estrogen on mammary epithelium. In premenopausal women, elevated testosterone is not associated with greater breast cancer risk. The risk of breast cancer is also not increased in women with polycystic ovary syndrome who have chronic estrogen exposure and androgen excess. However, in postmenopausal women, who are oestrogen deplete and have increased adipose aromatase activity, higher testosterone has been associated with greater breast cancer risk. Conclusion: Available data indicate the inclusion of testosterone in estrogen–progestin regimens has the potential to ameliorate the stimulating effects of hormones on the breast. However, testosterone therapy alone cannot be recommended for estrogen deplete women because of the potential risk of enhanced aromatisation to estrogen in this setting.