Treatment of climacteric symptoms in breast cancer patients: A retrospective study from a medication databank

Introduction

Women affected by breast cancer (BC) will often go through menopause at an earlier age and display more frequent and severe symptoms than women who have a natural menopause. The safety of hormone replacement therapy (HRT) and vaginal estrogens for BC survivors has been debated over time and remains unclear. Non hormonal therapies such as antidepressants, gabapentine and clonidine may be useful for those patients but there are few data about their safety.

Aim

This retrospective study analyses the use by BC patients of treatments known to alleviate climacteric symptoms.

Material and method

Post-menopausal Estrogen Receptors positive (ER+) BC patients, aged 45–69, were identified as having bought, at least once, an aromatase inhibitor (AI) or tamoxifen between the years 2000 and 2012 through a pharmaceutical databank in Belgium. Among them, we defined users of a climacteric treatment those who bought, at least once, HRT, vaginal topical estrogens, antidepressants, clonidine and gabapentine.

Results

We identified 2530 BC patients. Among them, 45% were buying a treatment known to alleviate menopausal symptoms. The majority of these treatments were non-HRT therapies. HRT and vaginal estrogens were seldom bought (respectively 1.1% and 6%), but 3% bought vaginal estrogens while buying AI. About 9.2% of tamoxifen users patients bought antidepressants implicated in tamoxifen metabolism at the same time as tamoxifen.

Conclusions

Most BC patients follow current guidelines contra-indicating the use of HRT after BC, they use non hormonal therapies. In some cases they use unfortunately antidepressants that may alter the metabolism of tamoxifen.     

Suspected black cohosh hepatotoxicity—Challenges and pitfalls of causality assessment

Objectives

Black cohosh (BC) is a herbal drug or herbal dietary supplement used for treatment of menopausal symptoms. Recently, however, reports have appeared about the occurrence of rare toxic liver disease in an assumed relationship with the use of BC.

Methods

We have analyzed and reviewed the data of all 69 reported cases with suspected BC hepatotoxicity. Causality for BC was assessed utilizing the scale of the original structured quantitative Council for International Organizations of Medical Sciences (CIOMS), or the main-test as its updated form.

Results

With the hepatotoxicity specific causality assessment methods, there was an excluded, unlikely, unrelated or unassessable causality for BC in 68 of 69 cases with liver disease. One patient had a possible causality for BC and a symptomatic cholelithiasis with confounding variables of fatty liver of unknown etiology; unknown BC brand including possible herbal mixture; unknown daily BC dosage; and an unassessable duration of BC usage. In general, the cases of the 69 patients were poorly documented. Confounding variables were: failure to identify the BC product; use of herbal mixtures with multiple ingredients in addition to BC; co-medication with synthetic drugs and dietary supplements including herbal ones; missing temporal association between BC use and development of liver disease; not specified modalities of BC treatment; failure of dechallenge after BC discontinuation; pre-existing liver diseases; insufficiently excluded other liver diseases; presence of alternative liver diseases.

Conclusions

The analysis of 69 cases shows little, if any, supportive evidence for a significant hepatotoxic risk of BC.     

Update of the evolution of breast cancer incidence in relation to hormone replacement therapy use in Belgium

Background

Several studies reported a decrease in breast cancer (BC) incidence, subsequent to the decrease in hormone replacement therapy (HRT) use.

Aim

Although Belgium has one of the highest incidences of BC in Europe and one of the highest rates of HRT use, we were unable, in a previous study, to observe a significant association between BC incidence and HRT changes. In this updated report we added the BC data from incidence years 2007 and 2008.

Material and method

We used European standardized incidence rates for invasive BC in the age class 50–69 years for Flanders (1999–2008), Brussels and Wallonia (2004–2008), obtained from IMS Health HRT sales data (1997–2008) for Brussels, Flanders and Wallonia. The association between BC incidence and HRT use was analyzed using generalized estimating equations (GEE) in order to take into consideration the dependency between the subsequent data points.

Results

There was a significant association between the invasive BC incidence rate and estimated rate of HRT users in the previous year: p-value < 0.001.

Conclusion

Although this study is hampered by a number of limitations, these data support the idea that the drop in BC incidence can be partly attributed to the decrease in HRT use. Since HRT remains the most used medication for climacteric symptoms, we encourage the creation of a prospective registry in Europe, collecting detailed data in various European countries, in order to assess the adjusted increase in BC risk associated with HRT, which may be population and regimen dependent.     

Central European BRCA2 mutation carriers: Birth cohort status correlates with onset of breast cancer

Background

Mutations in brca1 and 2 genes lead to a significant increase in the lifetime risk of developing breast (BC) and ovarian cancer (OC). There are indications that birth cohort can influence the cancer risk in brca1 mutation carriers. Therefore, we investigated the risks for BC and OC associated with brca2 mutations in a cohort of female mutation carriers of a genetically heterogeneous Central European population.

Patients and methods

This study included 246 women in whom a functional mutation in the brca2 gene had been identified at our institution. At the time of analysis, 153 women had developed cancer (142 BC, 9 OC, 2 BC and OC). Risks were estimated using the product limit method. The log rank test was used to compare different strata.

Results

After correction for risk-reducing surgeries, the cumulative risk of developing cancer to age 70 was found to be 88% for BC (95% CI 81–95%) and 31% for OC (95% CI 17–45%). Female brca2 mutation carriers born in 1958 or later were at a significantly higher risk of developing BC at a younger age (p < 0.001), while no such age cohort-dependent correlation was found for OC.

Conclusion

The age cohort-dependent early onset in BC in women born after 1958 strongly suggests the importance of exogenous factors such as lifestyle modification while this does not seem to be the case for OC. Female brca2 mutation carriers should be counseled about their age cohort-dependent breast cancer risk.     

Written notification of test results: Meanings, comprehension and implication on patients’ health behavior

Objective

Mailing test results are frequently used to provide patients with information about their medical condition and enhancing their participation in subsequent management. This study explores patients’ experiences of the written notification process and its implications.

Methods

Telephone interviews were conducted with 128 patients who had undergone endoscopic examinations in two gastroenterology clinics after the received of their mailed biopsies results. The interviews (open and closed questions) focused on patients’ perceptions and emotions while waiting, and after reading the reports.

Results

The findings are divided to emotions experienced, comprehension and behavioral implications. The reports arrived 6–33 days later than promised. Many patients were dissatisfied but most did nothing to hasten the process. Over half of them were unable to understand the information in the letters and the future steps needed to be taken. Explanatory covering letters, sent by the hospital clinic, enhanced comprehension and diminished confusion.

Conclusions

Mailed biopsy reports frequently failed to enhance patient understanding and participation in decisions. Incomprehensibility of written information, and unmet expectations, evoked negative emotional responses.

Practice implications

Improving readability with simple, non-technical information; and verification of understanding and fulfillment of recommendations using a follow-up call are critical for accomplishing the goals of mailed biopsy reports.     

Lifestyle influences on the association between pre-diagnostic hormone replacement therapy and breast cancer prognosis—Results from The Danish ‘Diet,Cancer and Health’ prospective cohort

Objectives

The association between pre-diagnostic hormone replacement therapy (HRT) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated.

Study design

Female participants from the prospective cohort “Diet, Cancer, and Health” diagnosed with breast cancer (BC) were identified and their pre-diagnostic HRT use evaluated for association with tumour biology and breast cancer outcome in multivariate analysis.

Main outcome measure

Breast cancer specific mortality.

Results

Of the 1212 patients originally considered 1064 were included. Of these, 105 women died from breast cancer during a median follow-up of 6.3 years (range 0.2–14.3 years). In multivariate analyses women who used HRT at enrolment into the cohort study had 47% lower risk of dying from breast cancer as compared to women who had previously or never used HRT (adjusted HR: 0.53; 95% CI, 0.37–0.85). Pre-diagnostic HRT use was associated with smaller tumour size at the time of diagnosis and a higher frequency of receptor positive breast cancer. Paradoxically, a high pre-diagnostic intake of vitamin D supplements was associated with HRT use but also with a higher BC specific mortality (HR: 1.47; 95% CI, 1.07–2.00)

Conclusions

HRT use at enrolment was associated with breast tumours of smaller size at the time of diagnosis and positive receptor status, and with a lower BC mortality. The found association between vitamin D from supplements and higher BC mortality warrants further exploration.     

Diagnosis of pseudoangiomatous stromal hyperplasia of the breast: ultrasonography findings and different biopsy methods

Purpose

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare, benign condition that can be mistaken as a fibroadenoma on an ultrasound examination or as a low-grade angiosarcoma on a histological examination. The objective of this study was to evaluate the ultrasound features and to present biopsy methods to correctly identify PASH.

Patients and Methods

We retrospectively reviewed the data of 55 women who were diagnosed with PASH of the breast. Ultrasound features were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS; American College of Radiology). The diagnostic ability of different biopsy methods such as core needle biopsy, vacuum-assisted biopsy and excisional biopsy were analyzed with the final histopathological results of surgical specimens.

Results

PASH presented as a circumscribed solid mass, with hypoechoic texture with or without heterogeneity, and a parallel orientation. The features of small, internal cysts or vascular channels and no calcifications can be used to differentiate the lesions from fibroadenomas. A core needle biopsy misdiagnosed PASH in 13 cases out of 28 cases and vacuum-assisted biopsy correctly identified PASH in all 3 cases.

Conclusion

Ultrasound features of PASH should be noted when performing a biopsy. For inconclusive cases of PASH, an excisional biopsy followed by an initial core biopsy should be performed.     

A cross-sectional study of elderly Asian and European women with primary operable breast cancer aged 70 and older. Are there differences?

Background

Breast cancer (BC) is becoming a disease of the elderly. Additionally, BC-incidence is rising in Asia. The aim of this study was to explore clinico-pathological characteristics and differences of breast cancer in elderly Asian/Han-Chinese compared to Caucasian/Austrian women.

Methods

A total number of 630 consecutive primary operable, unilateral breast cancer cases, 70 years and older, were analyzed. Histo-pathological findings and biological characteristics of 198 Caucasian/Austrian were compared with 432 Asian/Han-Chinese. Pearson's chi-square test was used to assess differences in the analyzed populations.

Results

A significantly higher rate of triple-negative BC (p = 0.027) was diagnosed among the Chinese geriatric population. More estrogen-receptor positive BC was detected in the Caucasian study group (p < 0.001). No statistically significant differences were detected based on tumor size, axillary lymph-node status, nor HER2-receptor expression.

Conclusion

This study will help us gain additional ethnic-specific insight into the biological characteristics of breast cancer in the elderly Caucasian/Austrian and Asian/Han-Chinese populations.     

A two-way text-messaging system answering health questions for low-income pregnant women

Objective

The purpose of the study was to gauge the effectiveness of a low-cost, automated, two-way text-messaging system to distribute pregnancy and health-related information to low-income expectant women.

Methods

In total, 20 participants were recruited for a one-month intervention involving the use of cell phones to text pregnancy-related questions to the system. Participants received either a direct answer or encouragement to seek answers from health care providers. Pre- and post-tests as well as a focus group at the end of the intervention were conducted.

Results

Participants uniformly found the system easy to use and accessible. Using the system increased levels of perceived pregnancy-related knowledge and facilitated patient-provider communication. Moreover, participants reported significant reductions in stress and depression and improved mental health after using the system. The system responded to most known questions quickly and accurately, and also encountered many new topics and linguistic expressions.

Conclusion

Overall, the data indicated that the text messaging system offered psychological benefits and promoted health communication by providing health information and encouraging patient-provider communication.

Practice implications

An automated, two-way text messaging system is an efficient, cost-effective, and acceptable method for providing health information to low-income pregnant women.     

Lost in translation?: Comparing three Scandinavian translations of the Beliefs about Medicines Questionnaire

Objective

The “Beliefs about Medicines Questionnaire” (BMQ) assess balance of necessity and concern of medicines. The BMQ has been translated from English to many languages. However, the original meaning of statements, such as “My medicine is a mystery to me”, may be lost in translation. The aim of this study is to compare three Scandinavian translations of the BMQ. (1) How reliable are the translations? (2) Are they still valid after translation?

Methods

Translated Norwegian, Swedish and Danish versions of the BMQ were scrutinized by three native Scandinavian researchers. Linguistic differences and ambiguities in the 5-point Likert scale and the BMQ statements were compared.

Results

In the Scandinavian translations, the Likert scale expanded beyond the original version at one endpoint (Swedish) or both endpoints (Danish). In the BMQ statements, discrepancies ranged from smaller inaccuracies toward completely different meaning. Some dissimilarities reflect different cultural beliefs about medicines.

Conclusion

When translating questionnaires, bilingual researchers should scrutinize translations across similar languages to address content validity across different countries and languages.

Practice implications

Our findings are of relevance to other BMQ translations in non-English countries, as direct comparisons between different translations might not be reliable or valid.     

Dose-dependent effect of resveratrol on bladder cancer cells: chemoprevention and oxidative stress

Background

Over 6 million people die annually in the world because of cancer. Several groups are focused on studying cancer chemoprevention approaches. Resveratrol, a polyphenol, at high dosages, has been reported as antitumor and chemopreventive. However, it has a dose-dependent effect on cell death, even on some cancer cells.

Objectives

Our aim was to investigate this dose-dependent effect on human bladder carcinoma ECV304 cells during oxidative stress condition.

Methods

For this purpose, ECV304 cells incubated with different Resveratrol concentrations were analyzed as for their metabolic rate, membrane permeability, DNA fragmentation, anti/proapoptotic protein levels and phosphatidylserine exposure after oxidative stress.

Results

Resveratrol induced cell death at high concentrations (>20 μM), but not at low ones (0.1–20 μM). Pretreatment with 2.5 μM protected the cells from oxidative damage, whereas 50 μM intensified the cell death and significantly increased Bad/Bcl-2 ratio (proapoptotic/antiapoptotic proteins). Resveratrol was able to modulate NO and PGE₂ secretion and performed an anti-adhesion activity of neutrophils on PMA-activated ECV304 cells.

Conclusions

Resveratrol at high doses induces cell death of ECV304 cells whereas low doses induce protection. Modulation of Bcl-2 protein induced by Resveratrol could be mediating this effect. This information about the role of Resveratrol on cancer alerts us about its dose-dependent effects and could lead the design of future chemoprevention strategies.     

Affective temperaments and ego defense mechanisms associated with somatic symptom severity in a large sample

Background

Several complex mechanisms including biological, psychological and social factors may contribute to the development of bodily symptoms. Affective temperaments may represent heritable subclinical manifestations of mood disorders, and the concept of ego defense mechanisms has also provided a model for the comprehension of psychopathology. The relationship between affective temperaments, defensive functioning and somatic symptom severity remains unknown.

Methods

We obtained data from a subsample of the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). Participants completed the Affective and Emotional Temperament Composite Scale (AFECTS), the Defense Style Questionnaire (DSQ-40) and the Symptom Checklist-90-Revised (SCL-90-R). SCL-90-R Somatization scale was used as outcome variable.

Results

Among 9937 participants (4472 male; 45%), individuals with dysphoric, cyclothymic and depressive temperaments and those who adopted displacement, somatisation and passive aggression as their predominant defense mechanisms presented high somatic symptom severity. Participants with dysphoric temperament and those with higher displacement scores were more likely to endorse numerous bodily symptoms after controlling for age, gender, education and depressive symptoms. Moderator analysis showed that the relationship of dysphoric temperament with somatic symptom severity was much more powerful in people who adopted displacement as their predominant defense.

Limitations

The data was collected from a convenience web-based sample. The study was cross-sectional. There was no information on the presence of established physical illness.

Conclusions

Affective temperaments and defense mechanisms are associated with somatic symptom severity independently of depressive symptoms. These two personality theories provide distinct but interacting views for comprehension of somatic symptom formation.     

Menopausal hormone therapy use in 17 European countries during the last decade

Introduction

The first ‘Women's Health Initiative’ (WHI) randomised controlled trial assessed use of continuous combined menopausal hormone therapy (cc-MHT). It was prematurely stopped because of an increased invasive breast cancer (BC), coronary heart disease (CHD), stroke and pulmonary embolism risk. Consequently, scientific societies recommended use of MHT at the lowest effective dose for the shortest duration. As a result, a sharp decline in MHT use occurred worldwide.

Aim

To report in a uniform way the change in MHT use in European countries. To evaluate whether the variability of the MHT changes were related to some medical indicators.

Materials and methods

IMS Health provided MHT sales data for the years 2002 till 2010 for 17 countries. We tested several hypotheses to explain the heterogeneity of MHT use changes.

Results and discussion

In 2002, the estimated MHT rate in women 45–69 years old varied considerably between countries ranging from less than 5% to more than 25%. In all countries a profound decrease occurred between 2002 and 2010, ranging from 50% to 77%. By the end of 2010, the MHT uptake was lower than 10% in all countries except in Finland. MHT use change was not correlated to MHT use and prevailing BC incidence at baseline, nor to the number of gynaecologists per 100,000 women or to the level of information about MHT.

Conclusion

The global MHT use experienced a sharp decrease in all the analysed countries, although some variability exists. The decrease was unrelated to the assessed parameters.     

Development and pilot testing of a novel education method for training medical interpreters

Objective

The goal of this study was to determine core competencies by means of a systematic literature review and to design and test an interpreter training program.

Methods

Core competencies in medical interpreting were searched using a systematic literature review. An intervention program was developed to improve core competencies. Pretests and posttests were conducted to pilot-test knowledge and interpreting skills in participants aged 22–62 years (n = 43). Results of the tests were compared.

Results

Results of the systematic review indicated five core competencies: (a) maintaining accuracy and completeness; (b) medical terminology and understanding the human body; (c) behaving ethically and making ethical decisions; (d) nonverbal communication skills; and (e) cross-cultural communication skills. Statistical analysis showed a significant improvement in knowledge and interpreting skills in the intervention program compared with the control program.

Conclusion

Posttest assessment showed that the developed training system can be useful in improving knowledge and quality in medical interpreting.

Practice implications

A 3-day training program for medical interpreters could bridge the gap between medical professionals and patients with limited English proficiency while being amenable to integration into clinical flow.     

Variations in meanings of the personal core value "health"

Objective

Preventive health behavior patterns and practices are influenced by many factors. Knowledge about a person's core values may improve the ability to predict decisions related to behaviors such as healthy eating.

Methods

In this cross-case comparison study, we illuminate the meanings ascribed to the core value “health” in relationship to fruit and vegetable intake for colorectal cancer survivors and for persons with no cancer history.

Results

We found that both survivors and non-survivors gave three accounts of how the value “health” influenced having a healthy diet. These were: (1) good health was necessary to fulfill/attain other values; (2) health was a manifestation of God's will; and (3) good health was not possible unless one values responsibility.

Conclusion

Understanding a person's core values provides insight about how values may act as motivators for behavior change.

Practice implications

Practitioners using motivational interviewing techniques should include a values clarification exercise to improve their assessment of how values influence behaviors.     

Clinicopathologic features and outcomes of metaplastic breast carcinoma: comparison with invasive ductal carcinoma of the breast

Purpose

Metaplastic breast carcinoma (MBC) is rare. Its clinicopathologic features and prognosis are uncertain. The aim of this study was to evaluate the clinicopathologic characteristics and outcomes in comparison with invasive ductal carcinoma (IDC).

Materials and Methods

We reviewed the data of 29 patients with MBC and 4,851 patients with IDC, who received surgery at Yonsei University Severance Hospital between 1980 and 2008. Various clinicopathologic features, recurrence free, and overall survival were investigated and compared to each other.

Results

Stage IV cases at diagnosis were more common in MBC (10.3%) than in IDC (0.9%). The incidence rates of triple negative breast cancer (TNBC) were significantly higher in MBC (84.0%) than in IDC (20.1%). Larger tumors (>2 cm) and lower tendency of axillary metastasis were frequently observed in MBC. Only one of 24 preoperative core needle biopsies (CNB) correctly diagnosed MBC. There was no significant difference in survival between the two groups.

Conclusion

MBC was characterized by a higher incidence of TNBC, larger tumor size, and lower tendency of axillary metastasis, and was difficult to diagnose with CNB. Although the incidence of stage IV disease at diagnosis was higher in MBC, the survival rates of stage I-III were comparable to those of IDC.     

Meta-analysis of differentially expressed genes in primary Sjogren’s syndrome by using microarray

Introduction

The purpose of this study was to identify differentially expressed (DE) genes and biological processes associated with changes in gene expression in primary Sjogren’s syndrome (pSS).

Methods

We performed a meta-analysis using the INMEX program (integrative meta-analysis of expression data) of publicly available microarray GEO datasets of pSS. We performed Gene Ontology (GO) enrichment analyses and pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results

Three GEO datasets including 37 cases and 33 controls were available for the meta-analysis. We identified 179 genes across the studies which were consistently DE in pSS (146 up-regulated and 33 down-regulated). The up-regulated gene with the largest effect size (ES) (ES = −2.4228) was SELL (selectin L), whose product is required for the binding and subsequent rolling of leucocytes on endothelial cells to facilitate their migration into secondary lymphoid organs and inflammation sites. The most significant enrichment was in the immune response GO category (P = 2.52 × 10⁻²⁵). The most significant pathway in our KEGG analysis was Epstein–Barr virus infection (P = 9.91 × 10⁻⁰⁶).

Conclusions

Our meta-analysis demonstrated genes that were consistently DE and biological pathways associated with gene expression changes with pSS.     

Education in patient–physician communication: How to improve effectiveness?

Objective

Despite educational efforts expertise in communication as required by the CanMEDS competency framework is not achieved by medical students and residents. Several factors complicate the learning of professional communication.

Methods

We adapted the reflective–impulsive model of social behaviour to explain the complexities of learning professional communication behaviour. We formulated recommendations for the learning objectives and teaching methods of communication education. Our recommendations are based on the reflective–impulsive model and on the model of deliberate practice which complements the reflective–impulsive model. Our recommendations are substantiated by those we found in the literature.

Results

The reflective–impulsive model explains why the results of communication education fall below expectations and how expertise in communication can be attained by deliberate practice. The model of deliberate practice specifies learning conditions which are insufficiently fulfilled in current communication programmes.

Conclusion

The implementation of our recommendations would require a great deal of effort. Therefore we doubt whether expertise in professional communication can be fully attained during medical training.

Practice implications

We propose that the CanMEDS communication competencies not be regarded as endpoints in medical education but as guidelines to improve communication competency through deliberate practice throughout a professional career.     

The International Charter for Human Values in Healthcare: An interprofessional global collaboration to enhance values and communication in healthcare

Objectives

The human dimensions of healthcare—core values and skilled communication necessary for every healthcare interaction—are fundamental to compassionate, ethical, and safe relationship-centered care. The objectives of this paper are to: describe the development of the International Charter for Human Values in Healthcare which delineates core values, articulate the role of skilled communication in enacting these values, and provide examples showing translation of the Charter's values into action.

Methods

We describe development of the Charter using combined qualitative research methods and the international, interprofessional collaboration of institutions and individuals worldwide.

Results

We identified five fundamental categories of human values for every healthcare interaction—Compassion, Respect for Persons, Commitment to Integrity and Ethical Practice, Commitment to Excellence, and Justice in Healthcare—and delineated subvalues within each category. We have disseminated the Charter internationally and incorporated it into education/training. Diverse healthcare partners have joined in this work.

Conclusion

We chronicle the development and dissemination of the International Charter for Human Values in Healthcare, the role of skilled communication in demonstrating values, and provide examples of educational and clinical programs integrating these values.

Practice implications

The Charter identifies and promotes core values clinicians and educators can demonstrate through skilled communication and use to advance humanistic educational programs and practice.