Is it best to expect the worst? Influence of patients' side-effect expectations on endocrine treatment outcome in a 2-year prospective clinical cohort study.

BACKGROUND: This study aims to determine the role of patient expectations as potentially modifiable factor of side-effects, quality of life, and adherence to endocrine treatment of breast cancer. PATIENTS AND METHODS: A 2-year prospective clinical cohort study was conducted in routine primary care with postoperative patients with hormone-receptor-positive breast cancer, scheduled to start adjuvant endocrine treatment. Structured patient-reported assessments of side-effects, side-effect expectations, quality of life, and adherence took place during the first week post-surgery and after 3 and 24 months of endocrine treatment. RESULTS: Of 111 enrolled patients, at 3 and 24 months, 107 and 88 patients, respectively, were assessed. After 2 years of endocrine treatment, patients reported high rates of side-effects (arthralgia: 71.3%, weight gain: 53.4%, hot flashes: 46.5%), including symptoms not directly attributable to the medication (breathing problems: 28.1%, dizziness: 25.6%). Pre-treatment expectations significantly predicted patient-reported long-term side-effects and quality of life in multivariate models controlling for relevant medical and psychological variables. Relative risk of side-effects after 2 years of endocrine treatment was higher in patients with high negative expectations at baseline than in those with low negative expectations (RR = 1.833, CI 95%, 1.032-3.256). A significant interaction confirmed this expectation effect to be particularly evident in patients with high side-effects at 3 months. Furthermore, baseline expectations were associated with adherence at 24 months (r = -0.25, P = 0.006). CONCLUSIONS: Expectations are a genuine factor of clinical outcome from endocrine treatment for breast cancer. Negative expectations increase the risk of treatment-specific side-effects, nocebo side-effects, and non-adherence. Yet, controlled studies are needed to analyze potential causal relationships. Optimizing individual expectations might be a promising strategy to improve side-effect burden, quality of life, and adherence during longer-term drug intake. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02088710.

Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel.

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients.

Persistency with estrogen replacement therapy among hysterectomized women after the Women's Health Initiative study.

OBJECTIVES: Many women are reluctant to undergo estrogen replacement therapy (ERT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of ERT in hysterectomized women over the past decade, reflecting changes in the post-Women's Health Initiative (WHI) era. METHODS: We analyzed 8045 patients receiving ERT from 2004 to 2013 using the Disease Analyzer database. RESULTS: After 12 months of follow-up, only 24.6% of patients receiving 1 mg and 24.5% of patients receiving 2 mg of oral ERT were still on treatment (p < 0.0001). The persistency rate of patients receiving <50 µg of transdermal ERT was 28.6% compared to 33.5% for patients receiving >50 µg within the 12 months of follow-up. ERT that began in 2007-2009 was associated with a higher discontinuation rate (hazard ratio 1.06, p = 0.0660) than ERT that began in 2010-2013 (hazard ratio 0.88, p = 0.0001). CONCLUSIONS: Our results indicate low persistency rates in women on ERT irrespective of the dose as well as the route of administration. However, a decrease in discontinuation rates was found when comparing women in the early vs. late post WHI era.

Discontinuation rates of menopausal hormone therapy among postmenopausal women in the post-WHI study era.

OBJECTIVES: Many women are reluctant to take menopausal hormone therapy (MHT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of combined MHT in the last decade, reflecting changes in the post-Women's Health Initiative era. METHODS: We analyzed 17 020 patients receiving combined MHT from 2004 to 2013 using the Disease Analyzer database. RESULTS: After 12 months of follow-up, 44.6% and 33.5% of patients receiving 1 mg and 2 mg, respectively, of oral combined MHT were still on treatment (p < 0.0001). The persistence rate of patients receiving < 50 µg of transdermal MHT was 39.1% after 1 year of treatment and presented no differences compared to patients receiving ≥ 50 µg of transdermal MHT with a persistence rate of 38.2%. MHT start in the years 2007-2009 was associated with higher discontinuation rates (hazard ratio 1.04, p = 0.0709) than MHT start in the years 2010-2013 (hazard ratio 0.90, p = 0.0001). CONCLUSIONS: Our results indicate that patients beginning their treatments in the years 2010-2013 were more treatment-persistent than patients beginning with MHT in the early years after publication of the Women's Health Initiative study (2004-2009). Administration of low-dose oral MHT and transdermal MHT is associated with increased persistency compared to higher doses of oral MHT.

Effects of zoledronic acid versus placebo on bone mineral density and bone texture analysis assessed by the trabecular bone score in premenopausal women with breast cancer treatment-induced bone loss: results of the ProBONE II substudy.

UNLABELLED: Changes in bone mineral density (BMD) and trabecular bone score (TBS) were assessed in 70 patients who received either zoledronate (ZOL) (n = 34) or placebo (n = 36) for 2 years. In premenopausal women with breast cancer treatment-induced bone loss, 24 months of intravenous ZOL treatment significantly increased the lumbar spine BMD and the TBS. INTRODUCTION: The aim of this study was to compare the effects of 4 mg intravenous zoledronate (ZOL) versus placebo (PLB), every 3 months, on the lumbar spine (LS) bone mineral density (BMD) and the trabecular bone score (TBS) in premenopausal women with breast cancer (BC) treatment-induced bone loss. The TBS is a gray-level texture measurement which is related to the bone microarchitecture and considered to be independent of the BMD. METHODS: Changes in BMD and TBS were assessed in 70 patients who were recruited in the double-blind, placebo-controlled ProBONE-II trial and randomized to receive either ZOL (n = 34) or PLB (n = 36) for 2 years. The changes were assessed at baseline and at 12 and 24 months after treatment initiation. RESULTS: Patients receiving ZOL showed a mean increase in LS BMD from the baseline to 12 (2.17%) and 24 months (3.14%) of treatment and a mean increase in the TBS of 2.41 and 0.75%, respectively. Conversely, patients receiving PLB showed a mean decrease in the LS BMD from the baseline to 12 (-5.02%) and 24 (-6.43%) months and a mean decrease of -0.52 and -2.16% in the TBS, respectively. Changes in the BMD and the TBS from the baseline to 12 and 24 months were all significantly different for ZOL compared to PLB (p < 0.005). Furthermore, BMD and TBS showed a moderate correlation ranging from 0.28 (p = 0.087) to 0.47 (p = 0.003). CONCLUSIONS: In premenopausal women with BC, 24 months of intravenous ZOL treatment significantly increased the LS BMD as well as the TBS.

Effect of anastrozole on hormone levels in postmenopausal women with early breast cancer.

OBJECTIVES: The aim of this study was to investigate the influence of anastrozole on serum hormone levels in postmenopausal women with hormone receptor-positive breast cancer. METHODS: We prospectively determined serum levels of estradiol, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and luteinizing hormone (LH) at screening, as well as after 12 and 24 months of treatment and studied the associations with markers of bone turnover and bone mineral density (BMD). RESULTS: Altogether, a full set of hormone levels was available for 70 patients. Anastrozole treatment led to decreases of 92.1% for estradiol and 11.1% for LH over the observation period (p < 0.001). Conversely, FSH, DHEAS and testosterone concentrations increased by 5.9%, 33.3% and 50%, respectively (p < 0.001). SHBG levels remained stable during the 24 months of treatment (p = 0.355). There were modest associations between FSH, SHBG, CrossLaps and N-terminal propeptide of human procollagen type I (p < 0.05). Moreover, SHBG correlated positively with the BMD of femoral neck, total hip, total hip T-score, lumbar spine and the lumbar spine T-score, whereas FSH and estradiol correlated with the lumbar spine T-score (p < 0.05). CONCLUSIONS: During the 24 months of follow-up, treatment with anastrozole decreased the serum levels of estradiol and LH. Furthermore, we found notable increases of serum levels of FSH, DHEAS and testosterone in the first 12 months of treatment, stabilizing thereafter. Additionally, we were able to correlate hormone levels with markers of bone turnover and BMD for the first time in this regard.

[Systematic assessment and improvement of medical data quality]. / Systematische Bewertung und Steigerung der Qualität medizinischer Daten.

Public health research depends on empirical information that is based on data of high quality. The aim of this study was to apply the current guidelines developed by the Technology and Methodology Platform for Networked Medical Research (TMF) for the independent assessment and enhancement of data quality. A clinical register of female breast cancer patients from two periods (N = 389 of 1996-1997 and N = 488 of 2003-2004) was used. To check the plausibility, organization, and correctness of the data quality levels, data quality indicators (DQI) were chosen, operationalized, and the variance ratios of normative-analytic-defined thresholds were calculated. Significant deviations led to data improvement, which included the commonly known source data verification (SDV). A summary data quality score was calculated before and after application of the guidelines. Eleven out of 24 DQIs were tested. Data quality systematically increased from 51.6 to 67.7%. The guidelines facilitate a systematic assessment and improvement of data quality with a reasonable use of resources. This target-oriented procedure allows for a high transparency of the available data quality, which is essential for health research.

[The population-based mammography screening programme in Germany: uptake and first experiences of women in 10 federal states]. / Das populationsbezogene Mammografie-Screening-Programm in Deutschland: Inanspruchnahme und erste Erfahrungen von Frauen in 10 Bundesländern.

PURPOSE: Within the statutory health insurance (SHI) cancer early detection programme (KFU) an organised, population-based, quality-assured mammographic screening programme in Germany was initiated for women aged 50-69 years in 2004. The aim of the study was to evaluate uptake and first experiences of participants with this new screening approach and to evaluate the background of knowledge, attitudes and intention to address a needs-assessed communication strategy. MATERIALS AND METHODS: A representative, explorative survey within the female population was conducted in 10 federal states. A telephone survey of randomly selected 68,188 contacts was performed, 9,004 women gave informed consent to evaluate rates of invitation and uptake followed by a mailed questionnaire. Of these, 3,469 were returned and 3,226 were analysed. RESULTS: The invitation rate of the programme was 56.6%, the uptake of mammographic screening was 66%, and the screening coverage rate was 37.3%. 90% of the participants were insured by SHI, women with lower socio-economic strata were attracted in accordance with the data of the general population. 61% of all women did not know that the risk of breast cancer increases with age and 56% believed that screening prevents breast cancer. 62.1% judged their own risk to be low. A physician's recommendation to participate was significantly associated with attendance (p<0.05). 90% of the participants would follow the next invitation. CONCLUSION: The KFU targeted group of women was reached and the organised mammography screening programme was well perceived by invited women. For developing a lasting communication strategy information deficits have to be considered along with beliefs and attitudes of elegible women.

Assessment of fracture risk in women with breast cancer using current vs emerging guidelines.

BACKGROUND: Breast cancer (BC) therapies can have negative effects on bone. Current guidelines recommend antiresorptive therapy based on bone mineral density (BMD), and emerging guidelines include both clinical risk factors and BMD to assess the overall fracture risk. A retrospective, case-controlled study based on current and emerging guidelines was conducted in women with newly diagnosed BC to identify those who were at increased fracture risk based on current and emerging guidelines. METHODS: Baseline characteristics, fracture risk factors, and lumbar-spine (LS) and total-hip BMD in women with BC (88 premenopausal and 402 postmenopausal) were assessed to determine who would receive bisphosphonate therapy based on current and emerging guidelines. RESULTS: Among patients with estrogen-receptor-positive (ER(+)) BC, 18.8% of premenopausal and 36.9% of postmenopausal women were osteopenic at LS. In the postmenopausal cohort, osteoporosis was more prevalent in patients with ER(+) vs ER(-) BC. Current guidelines identified 8.9% of patients as eligible for antiresorptive therapy, clinical risk factors alone identified 6.5%, and BMD plus clinical risk factors identified 28.6%. CONCLUSIONS: In addition to fracture risk factors present at BC diagnosis, cancer therapies leading to BMD loss further increase fracture risk. Evaluating both BMD and clinical risk factors may allow more effective identification of BC patients with elevated fracture risk.

Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer.

BACKGROUND: The level of adherence of various pharmacological therapies in chronic diseases varies, but is predominantly low. With tamoxifen (TAM), 23% and 50% nonadherence after 1 and 4 years have been reported. Day-to-day clinical observation suggests that adherence may even be lower with aromatase inhibitors, but limited data exist on the situation in daily clinical routine. The aim of this study was to evaluate the rate of adherent patients in a randomly selected sample of postmenopausal women with primary breast cancer, who had been assigned to an adjuvant endocrine treatment with TAM or anastrozole (ANA). MATERIALS AND METHODS: We investigated a random sample of 100 postmenopausal women with breast cancer (50 TAM and 50 ANA) who had received surgery for their primary breast cancer at our hospital in 2004/2005 and thereafter had been assigned to an adjuvant endocrine treatment. We evaluated the adherence rate with a detailed questionnaire and additionally carried out a retrospective prescription check of the hospital chart as well as calling the local physicians of our patients. A patient was counted as adherent with a self-reported tablet intake of 80% or more and if a medication possession ratio of 80% or more was achieved. RESULTS: Regarding the baseline characteristics, a significant difference in mean age was noticed in women on ANA versus TAM [65 (+/-3) and 72 (+/-3); P<0.001]. All women on TAM and ANA reported to be adherent (100%). After controlling for prescriptions, only 40 (80%) and 27 (69%) of the women on TAM and ANA were still classified as adherent (P<0.01 and P<0.01 versus self-report). We found no significant correlation of adherence to any baseline characteristics or side-effects in a logistic regression model. CONCLUSIONS: An important goal of any therapeutic intervention is to achieve comparable efficacy in routine clinical practice to that demonstrated in randomised clinical trials. However, a similar magnitude of adherence will be necessary in routine clinical practice to assure comparable clinical effects. Our results further support the data on suboptimal adherence of women with breast cancer on adjuvant TAM treatment. Here, we evaluated for the first time the patient reported and real-world adherence on adjuvant ANA and were able to show a similarly low adherence compared with TAM. More prospective studies are needed to increase our understanding of the underlying reasons for nonadherence in women with breast cancer.

[Guideline for the Early Detection of Breast Cancer in Germany 2008. Recommendations from the short version]. / Stufe-3-Leitlinie Brustkrebs-Früherkennung in Deutschland 2008 : Auszug aus der Kurzfassung: Handlungsempfehlungen.

The updated 2008 German Guideline for Early Detection of Breast Cancer provides evidence-based and consensus-based recommendations of the knowledge gained by the German Society for Surgery and the German Society of Plastic, Aesthetic, and Reconstructive Surgeons together with 29 professional societies, associations, and nonmedical organizations. The guideline is meant to assist physicians, healthy women, and patients in medical decisions with recommendations regarding the diagnostic chain in early detection of breast cancer. In addition to these recommendations, the guideline also includes descriptions of quality assurance for resources, procedures, outcomes, and evaluation using a set of quality indicators. It updates the previous version from 2003. The guideline's recommendations are presented. They are described in detail in the full publication (in German) Geburtsh Frauenh 2008; 68:251-261. The long version of the Guideline, methods report, and evidence report are available on the internet at www.awmf-leitlinien.de (reg. no. 077/001) with free access.

[Lymphedema in patients with breast cancer--a consensus regarding diagnostics and therapy in patients with postoperative lymphedema after primary breast cancer]. / Lymphödem bei Mammakarzinom--Konsensus zur Sektoren übergreifenden Diagnostik und Therapie des postoperativen Lymphödems bei Patientinnen mit primärem Mammakarzinom.

UNLABELLED: Secondary lymphedema is one of the most frequent long-term side effects affecting up to 30% of all breast cancer patients after local surgical and radiation treatment. Destruction of the lymphatic system causes a progressive and chronic condition with functional impairments and disabilities limiting patients in their daily activities and involving nearly all aspects of their quality of life. Also, problems in the occupational area may be caused by lymphedema. The need for improving oncological management for early diagnosis and referral for effective treatment of lymphedema is a major goal of breast cancer heath care while survival improves. METHOD: A systematic consensus process was performed involving all relevant partners and providers of lymphedema health care to develop a practical documentation concept and make recommendations according to the evidence of clinical studies and currently available guidelines. RESULTS: A practical concept of documentation with defined assessment points was developed for evaluation and monitoring of lymphedema, which included the assessment of quality of life parameters with recognised instruments by the patient themselves. Consensus recommendations for the postoperative management, prevention, treatment and follow-up of breast cancer patients along a clinical algorithm for in- and outpatient care were finalized. CONCLUSION: With improved survival, long-term side effects with major impact on quality of life become a most important end point criteria of oncological treatment. The clearly defined documentation concept and the comprehensive recommendations for lymphedema management may assist clinicians and patients to make timely decisions about in- and outpatient health care practice to optimize the interface between acute medicine and rehabilitation. Patients' compliance with treatment and prevention routines will be as important as ensuring the continuity of care. A longitudinal prospective study evaluating the effectiveness and efficacy of the consensus recommendation is currently being implemented.

The status of neck node metastases in breast cancer--loco-regional or distant?

Metastases to cervical lymph nodes do not exclusively derive from malignancies of the head and neck area. In the literature the region where distant metastases of breast carcinomas to the neck occur is exclusively named "supraclavicular". The system established by head and neck surgeons regarding neck node topography allows interdisciplinary management of patients with cervical lymph node metastases from breast cancer. Twelve patients suffering from breast cancer who presented with cervical masses have been examined. Most lymph node metastases were found in the posterior triangle of the neck and at the caudo-jugular level, but some metastases were even found in the upper jugular levels. The results presented show that neck node metastases of breast cancer are located superiorly to the supraclavicular region in more than 50% of the cases. According to the AJCC Staging System for Breast Cancer metastases located in the supraclavicular fossa are assessed as loco-regional metastases (N3c). Lymph node metastases situated above the supraclavicular region are not mentioned, but should be considered as distant metastases. This important question remains unanswered and deserves clarification in the current classification of the AJCC Staging System for Breast Cancer.

[Ultrasound examination of the breast with 7.5 MHz and 13 MHz-transducers: scope for improving diagnostic accuracy in complementary breast diagnostics?]. / Mamma-Sonographie mit 7.5 MHz versus 13 MHz: Ist eine Verbesserung der diagnostischen Sicherheit im Rahmen der komplementären Mammadiagnostik möglich?

AIM: Complementary diagnostic methods in early diagnosis of breast cancer are used to increase diagnostic accuracy and minimize unnecessary invasive diagnostic procedures. Aim of the following prospective, open multicenter clinical study was to define the value of high-frequency breast ultrasound with 13 MHZ transducers compared to standard breast ultrasound with 7.5 MHz. METHOD: Data of 810 female patients, aged 45 to 60 years, with 819 suspicious breast lesions evaluated by four participating centres between October 1996 and December 1997. Standardised breast ultrasound was performed uniformly using a AU4 IDEA diagnostic ultrasound system by Esaote-Biomedica in addition to a standardised procedure of clinical examination and standard-2view-mammography. Analysis of all aquired data and the correlating histopathological findings was done by means of descriptive statistics on the basis of an access datafile (Version 2.0). RESULTS: The histopathological evaluation showed 435 benign and 384 malignant findings. Overall sensitivity and specificity of the clinical examination were 71.1 % and 88.9 % and for mammography 84.7 % and 76.5 %, respectively. Standard ultrasound with 7,5 MHz reached a sensitivity of 82,6 % and a specificity of 80.8 % high-frequency ultrasound with 13 MHz came to 87.2 % and 78.4 %, respectively. Regarding tumour size, mammography gave the highest sensitivity in detection of pre-invasive cancers (DCIS). High-frequency breast ultrasound (13 MHz) proved to have a higher diagnostic accuracy compared to standard breast ultrasound (7,5 MHz) regardless of tumour size. Sensitivity was especially improved in case of small invasive tumours (pT1a) with 78 % versus 56 %, respectively. CONCLUSIONS: We conclude that high-frequency ultrasound is a valueable additive tool especially in the diagnosis of small tumours, improving diagnostic safety and reducing unnecessary invasive diagnostic procedures.

Survival chances and psychological aspects of quality of life in patients with localized early stage breast cancer.

BACKGROUND: The present analysis focuses on the long term psychological reactions to early stage breast cancer. Two hypotheses were formulated. The first hypothesis draws a direct link between tumour size/survival chances and Quality of life (QoL): The better the survival chances, the better QoL ('biological danger model'). The second hypothesis assumes that localized early breast cancer has excellent prognosis (> 90% five year survival rate), and that therefore QoL differences between various forms of early breast cancer should be minimal ('medico-pragmatic model'). PATIENTS AND METHODS: In a defined rural area with 252.000 inhabitants (small-area-analysis), a total of n = 389 patients with primary breast cancer were recruited. For the present analysis we selected a subgroup (n = 269) from the cohort by tumour size (pTis, pT1a,b, pT1c, and pT2). QoL scores for global quality of life, emotional functioning and future perspective were computed according to the EORTC manual and compared to age-matched norm data of the German population. RESULTS: A total of 690 QoL questionnaires were obtained from n = 269 patients with comparable completion rates within the four subgroups (pTis, pT1a,b, pT1c, and pT2). For all four groups and in all scores there were improvements over time. Generally, pTis always scored highest, pT2 always lowest, the other two groups in between. After one year pTis patients had higher mean scores in global quality of life than the norm. In contrast, pT1a,b were considerably lower than the norm and the difference between these two was 17.2 score points. It seems that the small difference (3.5%) in five year survival chances between pTis and T1 a,b tumours transforms into marked differences regarding quality of life, thus supporting a biological danger model of the survival/QoL relationship. CONCLUSIONS: Our results show that physicians have to realise although their early breast cancer patients have excellent survival chances, psychological distress is present. From a clinical perspective we would recommend that early stage breast cancer patients, and especially patients with occult, pT1a,b tumours be informed about their excellent prognosis. In addition, cognitive therapy might help patients stop worrying about their cancer.

Short version of the Guideline: Early Detection of Breast Cancer in Germany. An evidence-, consensus-, and outcome-based guideline according to the German Association of the Scientific Medical Societies (AWMF) and the German Agency for Quality in Medicine (AeZQ).

The goal of the Guideline "Early Detection of Breast Cancer in Germany" is to assist physicians, healthy women, and patients in the decision-making process in favour of appropriate health care regarding early detection and diagnosis of breast cancer. The principle of early detection of breast cancer embraces the detection of non-invasive stages of breast cancer (UICC stage 0, carcinoma in situ), reducing the frequency of invasive breast cancer development, as well as the identification of breast cancer at an early stage (UICC stage I) having a chance of cure of more than 90%, as shown by a large number of trials. The Guideline summarized in the following paper is a precondition to establishing a nation-wide, comprehensive, quality-assurance program for the early detection and diagnosis of breast cancer. The resulting consequence should be a timely mortality reduction of breast cancer. The cure of early stage disease will additionally be achieved by less intensive treatment methods while largely maintaining the quality of life of breast cancer patients. Implementing the Guideline offers the possibility of a significant improvement in women's health care.

[Stage 3 recommendations--the early recognition of breast cancer in Germany. Abridged version for medical practitioners]. / Stufe-3-Leitlinie--Brustkrebs-Früherkennung in Deutschland Kurzfassung für Arzte.

The Aim of this level 3 good clinical practice guideline is to help physicians, women and patients in decision making about the appropriate health care for early detection of breast cancer. The principle of early detection of breast cancer comprise the detection and diagnosis of premalignant breast tumors (stage 0, Carcinoma in situ), risk reduction of cancer development as well as the detection and diagnosis of breast cancer at an early stage (stage I), with a 90% chance of cure as shown by a large number of clinical trials. To establish a nation wide, comprehensive quality assuring program for the early detection of breast cancer the guideline summarized in the following paper offers the basis for a timely mortality reduction of breast cancer. The cure of early stage disease will be additionally possible by less invasive treatment allowing patients to maintain quality of life. The guideline leads to a major improvement of women's health care.

[A guideline for guidelines--methodological report and use of the guideline women's information]. / Eine Leitlinie für Leitlinien: Die methodische Entwicklung und Anwendung der Leitlinie Fraueninformation.

UNLABELLED: Information and education is needed to empower autonomy and self-determination of patients (informed consent). Furthermore reliable and accurate medical information is necessary for patients who want to take an active part in medical decision-making. The aim of this work is to define the requirements helping to assure the development of good qualified information material relevant for women and female patients as "a guideline on women information". An example of its use is given by embeding this guideline in the guideline for early detection of breast cancer in Germany by defining the specific elements required for developing qualified information on this issue for women. METHODS: A systematic, stepwise methodological process according to a level two guideline of the German Association of the Scientific Medical Societies (AWMF) and the Agency for Quality in Medicine (AZQ) was performed with the following elements: 1. Establishing an expert panel, 2. Generating the guideline statements by a formal, consensus based nominal group process, 3. External review process and finding supportive partners for the guideline on women information, 4. Using the guideline for guidelines: implementing the concept in the guideline of early detection of breast cancer in Germany. RESULTS: The "guideline women information" comprises nine elements of quality assuring requirements for the development of gender-specific information material and eleven specific elements which directly relate to the guideline statements on early detection of breast cancer. After external review 30 organisations gave their written support for future implementation of the guideline. The "guideline women information" was integrated as a tool for quality assurance of lay information into the "guideline for early detection of breast cancer in Germany". CONCLUSION: The "guideline women information" is a systematically developed, consensus-based recommendation to improve the development of qualified lay information at the point of its process by defining gender-specific aspects required for good lay information and its evaluation. As a guideline for guidelines its use is demonstrated by integrating this guideline into the "guideline for early detection of breast cancer in Germany" to ensure the development of qualified guideline compliant information.