Management of bone metastasis and cancer treatment-induced bone loss during the COVID-19 pandemic: An international perspective and recommendations.

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management. At a virtual meeting of the Cancer and Bone Society in July 2020, an expert group shared experiences and solutions to this challenge, following which a questionnaire was sent internationally to the symposium's participants, to explore the issues faced and solutions offered. 70 respondents, from 9 countries (majority USA, 39%, followed by UK, 19%) included 50 clinicians, spread across a diverse range of specialties (but with a high proportion, 64%, of medical oncologists) and 20 who classified themselves as non-clinical (solely lab-based). Spread of clinician specialty across tumour types was breast (65%), prostate (27%), followed by renal, myeloma and melanoma. Analysis showed that management of metastatic bone disease in all solid tumour types and myeloma, adjuvant bisphosphonate breast cancer therapy and cancer treatment induced bone loss, was substantially impacted. Respondents reported delays to routine CT scans (58%), standard bone scans (48%) and MRI scans (46%), though emergency scans were less affected. Delays in palliative radiotherapy for bone pain were reported by 31% of respondents with treatments often involving only a single dose without fractionation. Delays to, or cancellation of, prophylactic surgery for bone pain were reported by 35% of respondents. Access to treatments with intravenous bisphosphonates and subcutaneous denosumab was a major problem, mitigated by provision of drug administration at home or in a local clinic, reduced frequency of administration or switching to oral bisphosphonates taken at home. The questionnaire also revealed damaging delays or complete stopping of both clinical and laboratory research. In addition to an analysis of the questionnaire, this paper presents a rationale and recommendations for adaptation of the normal guidelines for protection of bone health during the pandemic.

Osteoporosis management in hematologic stem cell transplant recipients: Executive summary.

BACKGROUND: Treatment advances have reduced the adverse events associated with hematopoietic stem cell transplant (HSCT) and led to an increased number of transplants performed. HSCT patients are living longer with concerns on long-term outcomes. Bone fragility and fracture are at the forefront for long-term morbidities post-HSCT. RESULTS: In HSCT recipients, evidence has accumulated to support recommendations for more extensive monitoring of bone fragility and more appropriate administration of osteoporosis pharmacotherapies for patients at high risk of bone loss and/or fracture. CONCLUSION: This executive summary reports and summarizes the main recommendations published previously, including bone assessment, dietary and lifestyle recommendations and osteoporosis medication.

Bone health in estrogen-free contraception.

Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity through binding to specific progesterone receptors. New estrogen-free contraceptive and its possible implication on bone turnover are discussed in this review. Insufficient bone acquisition during development and/or accelerated bone loss after attainment of peak bone mass (PBM) are 2 processes that may predispose to fragility fractures in later life. The relative importance of bone acquisition during growth versus bone loss during adulthood for fracture risk has been explored by examining the variability of areal bone mineral density (BMD) (aBMD) values in relation to age. Bone mass acquired at the end of the growth period appears to be more important than bone loss occurring during adult life. The major physiological effect of estrogen is the inhibition of bone resorption. When estrogen transcription possesses binds to the receptors, various genes are activated, and a variety modified. Interleukin 6 (IL-6) stimulates bone resorption, and estrogen blocks osteoblast synthesis of IL-6. Estrogen may also antagonize the IL-6 receptors. Additionally, estrogen inhibits bone resorption by inducing small but cumulative changes in multiple estrogen-dependent regulatory factors including TNF-α and the OPG/RANKL/RANK system. Review on existing data including information about new estrogen-free contraceptives. All progestins exert activity through binding to specific progesterone receptors; hereby, three different groups of progestins exist: pregnanes, gonanes, and estranges. Progestins also comprise specific glucocorticoid, androgen, or mineralocorticoid receptor interactions. Anabolic action of a progestogen may be affected via androgenic, anti-androgenic, or synadrogenic activity. The C 19 nortestosterone class of progestogens is known to bind with more affinity to androgen receptors than the C21 progestins. This article reviews the effect of estrogens and progestogens on bone and presents new data of the currently approved drospirenone-only pill. The use of progestin-only contraceptives leading to an estradiol level between 30 and 50 pg/ml does not seem to lead to an accelerate bone loss.

Bone health in childhood cancer: review of the literature and recommendations for the management of bone health in childhood cancer survivors.

In the past decades, new cancer treatment approaches for children and adolescents have led to a decrease in recurrence rates and an increase in long-term survival. Recent studies have focused on the evaluation of the late effects on bone of pediatric cancer-related treatments, such as chemotherapy, radiation and surgery. Treatment of childhood cancer can impair the attainment of peak bone mass, predisposing to premature onset of low bone mineral density, or causing other bone side-effects, such as bone quality impairment or avascular necrosis of bone. Lower bone mineral density and microarchitectural deterioration can persist during adulthood, thereby increasing fracture risk. Overall, long-term follow-up of childhood cancer survivors is essential to define specific groups at higher risk of long-term bone complications, identify unrecognized long-term adverse effects, and improve patient care. Children and adolescents with a cancer history should be carefully monitored, and patients should be informed of possible late complications of their previous medical treatment. The International Osteoporosis Foundation convened a working group to review the bone complications of pediatric cancer survivors, outlining recommendations for the management of bone health, in order to prevent and treat these complications.

Bone management in hematologic stem cell transplant recipients.

Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with some malignant and non-malignant hematological diseases. Advances in transplantation techniques and supportive care measures have substantially increased the number of long-term HSCT survivors. This has led to an increasing patient population suffering from the late effects of HSCT, of which, bone loss and its consequent fragility fractures lead to substantial morbidity. Altered bone health, with consequent fragility fractures, and chronic graft-versus-host disease (GVHD) are factors affecting long-term quality of life after HSCT. Hypogonadism, HSCT preparative regimens, nutritional factors, and glucocorticoids all contribute to accelerated bone loss and increased fracture risk. Management strategies should include bone mineral density examination, evaluation of clinical risk factors, and general dietary and physical activity measures. Evidence has accumulated permitting recommendations for more attentiveness to evaluation and monitoring of bone health, with appropriate application of osteoporosis pharmacotherapies to patients at increased risk of bone loss and fracture.

The tamoxifen paradox-influence of adjuvant tamoxifen on fracture risk in pre- and postmenopausal women with breast cancer.

Our data demonstrate that tamoxifen does not reduce fracture risk. Close surveillance is necessary to prevent bone loss in premenopausal women with breast cancer upon treatment initiation. INTRODUCTION: Endocrine treatment of breast cancer may interfere with bone turnover and influence fracture risk. METHODS: Out of a cohort of almost 5 million patients in total, we identified 5520 women between 18 and 90 years of age with breast cancer receiving tamoxifen, matched them with 5520 healthy controls using the Disease Analyzer Database, and investigated the fracture risk. RESULTS: We found a cumulative incidence of fractures of 6.3% in patients aged between 18 and 50 years (n = 3634) treated with tamoxifen versus a cumulative incidence of 3.6% in the control group (p < 0.001). As such, the risk of fracture was 75% higher for patients receiving tamoxifen than that for healthy controls (HR 1.75; 95% CI 1.25-2.48). With regard to patients aged between 55 and 90 years (n = 7406), the cumulative incidence of fractures in patients treated with tamoxifen was 10.1% compared to 9.3% in the control group (p = 0.740), i.e., there was no significant difference between the two groups (HR 0.97; 95% CI 0.81-1.16). CONCLUSIONS: Compared to healthy controls, premenopausal women with breast cancer treated with tamoxifen showed an increased risk of fracture, while postmenopausal women on tamoxifen did not show any risk reduction.

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study.

BACKGROUND: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. PATIENTS AND METHODS: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. RESULTS: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). CONCLUSIONS: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CLINICAL TRIALS NUMBER: CFEM345DDE19.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates.

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. INTRODUCTION: Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients. METHODS: The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. RESULTS: Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%. CONCLUSIONS: If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.

Bone health in the elderly cancer patient: A SIOG position paper.

More than a third of cancers are diagnosed in people over the age of 75. Androgen deprivation for prostate cancer and aromatase inhibitors in breast cancer accelerate age-related bone loss and increase fracture rates. BMD should be checked by dual energy X-ray absorptiometry at baseline and, dependent on risk, every 12-24months. Sufficient calcium, vitamin D and exercise are part of primary fracture prevention. Resistance exercise in particular may improve functional activity and bone density. In men at increased fracture risk and women with postmenopausal early breast cancer, antiresorptive treatment is warranted to reduce fracture rate and to increase overall survival in breast cancer. Bone metastases (BM) are common in breast and prostate cancer and lytic bone lesions typical of multiple myeloma. They can cause fractures, pain and spinal cord compression, require surgery or radiation for symptom relief, and lead to hypercalcaemia. Multidisciplinary working with patients and carers can improve quality of life for elderly patients with BM and mitigate the adverse consequences of therapy. Bisphosphonates and other osteoclast inhibitors such as denosumab reduce this morbidity, improve quality of life and reduce pain. Especially in the elderly, attention should be paid to renal function and to risk factors for osteonecrosis with bone-modifying agents. Attention should also be paid to hypocalcaemia risk, which can be considerable in elderly men with metastatic prostate cancer and vitamin D deficiency. We urgently need further research specifically directed at assessing risks and benefits of bone targeted treatments in the growing population of elderly cancer patients.

CE/BZA effects on bone and quality of life in European postmenopausal women: a pooled analysis.

OBJECTIVES: To evaluate the efficacy of conjugated estrogens/bazedoxifene (CE/BZA) on bone mineral density (BMD), bone turnover markers (BTM), and menopause-specific quality of life (MENQOL) in European women. METHODS: Data through 12 months were pooled from two double-blind, randomized, controlled trials in non-hysterectomized postmenopausal women who received CE/BZA or placebo. Women from European study sites with evaluable BMD (n = 60), BTM (n = 56), and MENQOL questionnaire (n = 236) data were included and compared with 1523 women from US study sites (n = 730 with evaluable data for bone outcomes). RESULTS: At month 12, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg, respectively, significantly improved BMD (adjusted difference vs. placebo) in lumbar spine (2.5%, 2.9%; both p ≤ 0.011) and total hip (1.7%, 2.2%, both p ≤ 0.002), significantly improved serum BTMs (osteocalcin: -31.1%, -33.1%; C-telopeptide: -48.5%, -36.8%) vs. placebo (osteocalcin: 6.7%, C-telopeptide: 4.2%; all p < 0.001), and significantly improved MENQOL vasomotor function scores (-2.1, -2.2) vs. placebo (-0.7; both p < 0.001). No significant treatment × subpopulation interactions were observed for any of the outcomes. CONCLUSIONS: Twelve-month CE/BZA treatment prevented bone loss and improved vasomotor function in European postmenopausal women. Findings were similar to those in the subpopulation of women enrolled at US study sites.

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.

Age-related differences in persistence with bisphosphonates in women with metastatic breast cancer.

AIMS: To investigate age-related persistence with bisphosphonates (BIS) in women with breast cancer (BC) and bone metastases. METHODS: We included a dataset of 1541 patients diagnosed with BC and bone metastases and initially treated with BIS between 1994 and 2013. The primary outcome measure was the age-related rate of BIS discontinuation within 12 months after treatment initiation. Therapy discontinuation was defined as a period of at least 90 days without treatment. A multivariate Cox regression model was created to determine the influence of age on the risk of discontinuation. Health insurance coverage (private/statutory), type of care (gynecological/general), region (West/East Germany), depression, chemotherapy, hormone therapy, pain medication, antidepressants, and the number of co-medications were included as covariates. RESULTS: The mean ages in the group of women <70 and that of women ≥70 years of age were 55.7 (SD: 9.8) and 76.7 (SD: 5.1) years respectively. Within 12 months after treatment initiation, 44.3% of women <70 and 34.8% of women ≥70 had terminated treatment (p-value<0.001). Patients aged ≥70 were at a lower risk of treatment discontinuation than patients <70 (HR=0.78, 95% CI: 0.67-0.91). Furthermore, treatment in gynecological practices, chemotherapy, hormone therapy, pain medication, and number of co-medications decreased the risk of discontinuation. By contrast, residing in West Germany and private health insurance coverage increased discontinuation risk. CONCLUSIONS: Women with metastatic BC aged ≥70 are at a lower risk of BIS treatment discontinuation than younger women.

Comparison of combined low-dose hormone therapy vs. tibolone in the prevention of bone loss.

OBJECTIVES: To compare the effects on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry at the lumbar spine, the femoral neck and the total hip following 2 years of treatment with a low-dose combined hormone therapy (HT) comprised of 1 mg estradiol and 0.5 mg norethisterone acetate (E2/NETA) versus 2.5 mg tibolone in postmenopausal women. Additionally, quantitative ultrasonometry (QUS) of the os calcaneus and of the phalanges was performed. METHODS: Changes in BMD, QUS and side-effects were assessed at baseline, 6, 12 and 24 months in 50 postmenopausal women who received either E2/NETA (n = 26) or tibolone (n = 24) for 2 years. RESULTS: Compared to women on tibolone, women receiving E2/NETA showed a significant increase in BMD from baseline to 12 and 24 months at the lumbar spine (3.07%, 3.86%; p < 0.01 vs. 1.13%, 2.23%; p < 0.05), and at the total hip (1.33%, 1.69%; p < 0.01 vs. 0.76%, 0.70%) and at the femoral neck from baseline to 24 months (1.10%; p < 0.05). QUS indices only showed a significant change with the ultrasound bone profile index with E2/NETA at 6 months (-2.32%; p < 0.001). CONCLUSIONS: Low-dose E2/NETA showed a significantly higher increase in BMD compared to tibolone. QUS measurement was not considered to comprise beneficial effects in monitoring drug-induced bone changes.

Depression risk in female patients with osteoporosis in primary care practices in Germany.

UNLABELLED: Thirty-five thousand four hundred eighty-three female osteoporosis patients were compared with 35,483 patients without osteoporosis regarding the incidence of depression. The risk of depression is significantly increased for patients with osteoporosis compared with patients without osteoporosis in primary care practices within Germany. INTRODUCTION: The objectives of the present study were to analyze the incidence of depression in German female patients with osteoporosis and to evaluate the risk factors for depression diagnosis within this patient population. METHODS: This study was a retrospective database analysis conducted in Germany utilizing the Disease Analyzer® Database (IMS Health, Germany). The study population included 70,966 patients between 40 and 80 years of age from 1072 primary care practices. The observation period was between 2004 and 2013. Follow-up duration was 5 years and was completed in April 2015. A total of 35,483 osteoporosis patients were selected after applying exclusion criteria, and 35,483 controls were chosen and then matched (1:1) to osteoporosis patients based on age, sex, health insurance coverage, depression diagnosis in the past, and follow-up duration after index date. The analyses of depression-free survival were carried out using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models (dependent variable: depression) were used to adjust for confounders. RESULTS: Depression diagnoses were presented in 33.0 % of the osteoporosis group and 22.7 % of the control group after the 5-year follow-up (p < 0.001). Dementia, cancer, heart failure, coronary heart disease, and diabetes were associated with a higher risk of developing depression (p < 0.001). Private health insurance was associated with a lower risk of depression. There was no significant effect of fractures on depression risk. CONCLUSION: The risk of depression is significantly increased for patients with osteoporosis in primary care practices within Germany.

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.

Biomarkers in Patients with Metastatic Breast Cancer and the PRAEGNANT Study Network.

Progress has been made in the treatment of metastatic breast cancer in recent decades, but very few therapies use patient or tumor-specific characteristics to tailor individualized treatment. More than ten years after the publication of the reference human genome sequence, analysis methods have improved enormously, fostering the hope that biomarkers can be used to individualize therapies and offer precise treatment based on tumor and patient characteristics. Biomarkers at every level of the system (genetics, epigenetics, gene expression, micro-RNA, proteomics and others) can be used for this. This has led to changes in clinical study designs, with drug developments often only focusing on small or very small subgroups of patients and tumors. The screening and registration of patients and their molecular tumor data has therefore become very important for the successful completion of clinical studies. This new form of medicine presents particular challenges for patients and physicians. Even in this new age of genome-wide analysis, the focus should still be on the patients' quality of life. This review summarizes recent developments and describes how the PRAEGNANT study network manages the aforementioned medical challenges and changes to create a professional infrastructure for patients and physicians.