Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis.

BACKGROUND: Bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are amongst the bone-modifying agents used as supportive treatment in women with breast cancer who do not have bone metastases. These agents aim to reduce bone loss and the risk of fractures. Bisphosphonates have demonstrated survival benefits, particularly in postmenopausal women. OBJECTIVES: To assess and compare the effects of different bone-modifying agents as supportive treatment to reduce bone mineral density loss and osteoporotic fractures in women with breast cancer without bone metastases and generate a ranking of treatment options using network meta-analyses (NMAs). SEARCH METHODS: We identified studies by electronically searching CENTRAL, MEDLINE and Embase until January 2023. We searched various trial registries and screened abstracts of conference proceedings and reference lists of identified trials. SELECTION CRITERIA: We included randomised controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for women with breast cancer without bone metastases. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of included studies and certainty of evidence using GRADE. Outcomes were bone mineral density, quality of life, overall fractures, overall survival and adverse events. We conducted NMAs and generated treatment rankings. MAIN RESULTS: Forty-seven trials (35,163 participants) fulfilled our inclusion criteria; 34 trials (33,793 participants) could be considered in the NMA (8 different treatment options). Bone mineral density We estimated that the bone mineral density of participants with no treatment/placebo measured as total T-score was -1.34. Evidence from the NMA (9 trials; 1166 participants) suggests that treatment with ibandronate (T-score -0.77; MD 0.57, 95% CI -0.05 to 1.19) may slightly increase bone mineral density (low certainty) and treatment with zoledronic acid (T-score -0.45; MD 0.89, 95% CI 0.62 to 1.16) probably slightly increases bone mineral density compared to no treatment/placebo (moderate certainty). Risedronate (T-score -1.08; MD 0.26, 95% CI -0.32 to 0.84) may result in little to no difference compared to no treatment/placebo (low certainty). We are uncertain whether alendronate (T-score 2.36; MD 3.70, 95% CI -2.01 to 9.41) increases bone mineral density compared to no treatment/placebo (very low certainty). Quality of life No quantitative analyses could be performed for quality of life, as only three studies reported this outcome. All three studies showed only minimal differences between the respective interventions examined. Overall fracture rate We estimated that 70 of 1000 participants with no treatment/placebo had fractures. Evidence from the NMA (16 trials; 19,492 participants) indicates that treatment with clodronate or ibandronate (42 of 1000; RR 0.60, 95% CI 0.39 to 0.92; 40 of 1000; RR 0.57, 95% CI 0.38 to 0.86, respectively) decreases the number of fractures compared to no treatment/placebo (high certainty). Denosumab or zoledronic acid (51 of 1000; RR 0.73, 95% CI 0.52 to 1.01; 55 of 1000; RR 0.79, 95% CI 0.56 to 1.11, respectively) probably slightly decreases the number of fractures; and risedronate (39 of 1000; RR 0.56, 95% CI 0.15 to 2.16) probably decreases the number of fractures compared to no treatment/placebo (moderate certainty). Pamidronate (106 of 1000; RR 1.52, 95% CI 0.75 to 3.06) probably increases the number of fractures compared to no treatment/placebo (moderate certainty). Overall survival We estimated that 920 of 1000 participants with no treatment/placebo survived overall. Evidence from the NMA (17 trials; 30,991 participants) suggests that clodronate (924 of 1000; HR 0.95, 95% CI 0.77 to 1.17), denosumab (927 of 1000; HR 0.91, 95% CI 0.69 to 1.21), ibandronate (915 of 1000; HR 1.06, 95% CI 0.83 to 1.34) and zoledronic acid (925 of 1000; HR 0.93, 95% CI 0.76 to 1.14) may result in little to no difference regarding overall survival compared to no treatment/placebo (low certainty). Additionally, we are uncertain whether pamidronate (905 of 1000; HR 1.20, 95% CI 0.81 to 1.78) decreases overall survival compared to no treatment/placebo (very low certainty). Osteonecrosis of the jaw We estimated that 1 of 1000 participants with no treatment/placebo developed osteonecrosis of the jaw. Evidence from the NMA (12 trials; 23,527 participants) suggests that denosumab (25 of 1000; RR 24.70, 95% CI 9.56 to 63.83), ibandronate (6 of 1000; RR 5.77, 95% CI 2.04 to 16.35) and zoledronic acid (9 of 1000; RR 9.41, 95% CI 3.54 to 24.99) probably increases the occurrence of osteonecrosis of the jaw compared to no treatment/placebo (moderate certainty). Additionally, clodronate (3 of 1000; RR 2.65, 95% CI 0.83 to 8.50) may increase the occurrence of osteonecrosis of the jaw compared to no treatment/placebo (low certainty). Renal impairment We estimated that 14 of 1000 participants with no treatment/placebo developed renal impairment. Evidence from the NMA (12 trials; 22,469 participants) suggests that ibandronate (28 of 1000; RR 1.98, 95% CI 1.01 to 3.88) probably increases the occurrence of renal impairment compared to no treatment/placebo (moderate certainty). Zoledronic acid (21 of 1000; RR 1.49, 95% CI 0.87 to 2.58) probably increases the occurrence of renal impairment while clodronate (12 of 1000; RR 0.88, 95% CI 0.55 to 1.39) and denosumab (11 of 1000; RR 0.80, 95% CI 0.54 to 1.19) probably results in little to no difference regarding the occurrence of renal impairment compared to no treatment/placebo (moderate certainty). AUTHORS' CONCLUSIONS: When considering bone-modifying agents for managing bone loss in women with early or locally advanced breast cancer, one has to balance between efficacy and safety. Our findings suggest that bisphosphonates (excluding alendronate and pamidronate) or denosumab compared to no treatment or placebo likely results in increased bone mineral density and reduced fracture rates. Our survival analysis that included pre and postmenopausal women showed little to no difference regarding overall survival. These treatments may lead to more adverse events. Therefore, forming an overall judgement of the best ranked bone-modifying agent is challenging. More head-to-head comparisons, especially comparing denosumab with any bisphosphonate, are needed to address gaps and validate the findings of this review.

Assessment of psychological distress in patients with cervical dysplasia according to age, education, information acquisition and information level.

PURPOSE: This study aims to investigate the psychological distress experienced by patients with an initial diagnosis of abnormal Pap smears or dysplastic changes of the cervix uteri. It investigated whether patients' age, education, information level and approach to information acquisition have an impact on their psychological distress. METHODS: A total of 364 female patients, aged 20-80 years, referred to the special dysplasia consultation hour at the Department of Obstetrics and Gynecology, Wuerzburg, completed a questionnaire containing validated items to assess information level, information acquisition, information needs and psychological distress, including a distress thermometer. Data from questionnaires and medical reports were used for analysis. RESULTS: The study found that 56.9% of patients experienced psychological distress before their first visit. Patients under 44 years of age, especially those with concerns about fertility and sexuality, and those with lower levels of education showed higher levels of distress (p-value = 0.018 and p-value = 0.037). 40.9% of patients felt poorly informed and 53.7% of patients wanted more information before their visit. Correlational analysis showed that the method of obtaining information correlated with the desire for more information (p-value < 0.001). Those who received information via the Internet felt less informed, wanted more information and experienced more anxiety. CONCLUSION: These findings highlight the need for improved patient education strategies and effective doctor-patient communication to address the knowledge gap and reduce patient distress. In addition, healthcare providers should ensure that patients have access to reliable online resources for accurate information.

Prevalence and Obstetric Management Changes During the COVID-19 Pandemic in Peripartum SARS-CoV-2-Positive Women - an Analysis of the CRONOS Registry Data.

The analysis of CRONOS data for this article presents the infection prevalence among parturients and subsequent changes in obstetric management over time in Germany. 2,184 women with peripartum SARS-CoV-2 infection (<14d before birth) were included. Monthly period prevalence was calculated using the number of affected women on the CRONOS registry relative to total monthly births in each hospital from March 2020 to May 2022 and compared to RKI data. Trends related to changes in obstetric management were calculated based on severity of illness. By June 2021, the obstetric population shows a discretely higher infection prevalence compared to the general population, falling below the RKI reported prevalence by October 2021. The overall rate of iatrogenic deliveries remains unchanged over time (p-value for trend=0.779). During wave 1 to 4, deliveries due to SARS-CoV-2 infection rose among moderately to severely ill women (p-value for trend 0.0000) and was increased compared to moderately ill women (p=0.001). We showed that comprehensive screening provides timely information on infection prevalence. Recruitment fatigue caused by higher clinician workload due to increased admissions and more cases with severe illness probably caused reduced prevalence reporting. Changes in obstetric management were related to COVID-19 symptom severity. A comprehensive national perinatal registry is needed to examine other areas of perinatal care in Germany.

Differences in Preferences for Drug Therapy Between Patients with Metastatic Versus Early-Stage Breast Cancer: A Systematic Literature Review.

INTRODUCTION: Compared with early stages (eBC) metastatic BC (mBC) is incurable. In mBC, aggressive treatment may increase the duration of survival but may also cause severe treatment side effects. A better understanding how patients with BC value different aspects of drug therapy might improve treatment effectiveness, satisfaction and adherence. This systematic review aims to identify and summarise studies evaluating patient preferences for drug therapy of BC and to compare preferences of patients with eBC and mBC. METHODS: The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The electronic databases PubMed and Web of Science were searched on 22 June 2023. All studies published to this point were considered. Original studies reporting patient preferences on BC drug therapy determined by any type of choice experiment were eligible. A narrative synthesis of the effect measures presented as relative importance ratings, trade-offs (required benefit to make a therapy worthwhile) or monetary values of the treatment attributes was reported for each study. Risk of bias assessment for individual studies was performed using the checklist for observational studies from the STROBE Statement and the checklist from 'Conducting Discrete Choice Experiments to Inform Healthcare Decision Making: A User's Guide'. The study protocol was registered at the PROSPERO database (CRD42022377031). RESULTS: A total of 34 studies met the inclusion criteria were included in the analysis evaluating the preferences of patients with eBC (n = 18), mBC (n = 10) or any stage BC (n = 6) on, for example, chemotherapy, endocrine therapy, hormonal therapy or CKD4/6-inhibitors using different types of choice experiments. Regardless of the stage, most patients valued treatment effectiveness in terms of survival gains higher than potential adverse drug reactions (ADRs). Treatment cost, mode of administration, treatment regimen and monitoring aspects were considered as least important treatment attributes. In addition, preferences concerning 16 different types of ADRs were described, showing high heterogeneity within BC stages. Yet, comparable results across BC stages were observed. CONCLUSIONS: Regardless of the stage, patients with BC consistently valued survival gains as the most important attribute and were willing to accept the risk of potential ADRs. Incorporating patient preferences in shared decision making may improve the effectiveness of interventions by enhancing adherence to drug therapy in patients suffering from BC.

Preferences of patients with breast cancer for drug therapy play a crucial role in treatment efficacy, satisfaction and adherence. In this systematic review following the PRISMA guidelines, 34 studies were analysed to determine patient preferences at different stages of breast cancer, comparing early stage and metastatic disease. Regardless of stage, patients with breast cancer consistently prioritised survival benefit as the most important treatment feature. This universal emphasis on survival held true even in the face of potential side effects, with patients willing to accept the associated risks. Conversely, factors unrelated to efficacy, such as the cost of treatment, route of administration, characteristics of the treatment regimen and monitoring aspects, were considered less important in treatment decisions. The study revealed a nuanced landscape of patient preferences, with greater variation within breast cancer stages than between them. While survival remained an unwavering priority, the variability in expressed preferences emphasises the individual nature of patient perspectives. In conclusion, incorporating patient preferences, particularly those that emphasise the importance of survival, into shared decision-making processes is a critical factor in improving treatment adherence. This patient-centred approach is likely to improve the overall effectiveness of breast cancer treatment and highlights the need for tailored strategies that take into account the individual preferences of patients at different stages of the disease.

Evaluating the value of individualized 3D printed models for examination, diagnosis and treatment planning of cervical cancer.

BACKGROUND: 3D printing holds great potential of improving examination, diagnosis and treatment planning as well as interprofessional communication in the field of gynecological oncology. In the current manuscript we evaluated five individualized, patient-specific models of cervical cancer FIGO Stage I-III, created with 3D printing, concerning their value for translational oncology. METHODS: Magnetic resonance imaging (MRI) of the pelvis was performed on a 3.0 Tesla MRI, including a T2-weighted isotropic 3D sequence. The MRI images were segmented and transferred to virtual 3D models via a custom-built 3D-model generation pipeline and printed by material extrusion. The 3D models were evaluated by all medical specialties involved in patient care of cervical cancer, namely surgeons, radiologists, pathologists and radiation oncologists. Information was obtained from evaluated profession-specific questionnaires which were filled out after inspecting all five models. The questionnaires included multiple-select questions, questions based on Likert scales (1 = "strongly disagree " or "not at all useful " up to 5 = "strongly agree " or "extremely useful ") and dichotomous questions ("Yes" or "No"). RESULTS: Surgeons rated the models as useful during surgery (4.0 out of 5) and for patient communication (4.7 out of 5). Furthermore, they believed that the models had the potential to revise the patients' treatment plan (3.7 out of 5). Pathologists evaluated with mean ratings of 3.0 out of 5 for the usefulness of the models in diagnostic reporting and macroscopic evaluation. Radiologist acknowledged the possibility of providing additional information compared to imaging alone (3.7 out of 5). Radiation oncologists strongly supported the concept by rating the models highly for understanding patient-specific pathological characteristics (4.3 out of 5), assisting interprofessional communication (mean 4.3 out of 5) and communication with patients (4.7 out of 5). They also found the models useful for improving radiotherapy treatment planning (4.3 out of 5). CONCLUSION: The study revealed that the 3D printed models were generally well-received by all medical disciplines, with radiation oncologists showing particularly strong support. Addressing the concerns and tailoring the use of 3D models to the specific needs of each medical speciality will be essential for realizing their full potential in clinical practice.

The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy-A Retrospective Multi-Center Cohort Study.

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.

Decision Coaching for Healthy Women With BRCA1/2 Pathogenic Variants.

BACKGROUND: Women with pathogenic variants (PV) of the genes BRCA1/2 have a choice of preventive options. To help these women decide for themselves, we developed and implemented a decision coaching (DC) program and evaluated it for congruence between the participants' desired and actual roles in decision-making. METHODS: Healthy BRCA1/2 PV carriers (25-60 years of age) were recruited at six centers in Germany. Those who returned baseline (T1) questionnaires were randomly assigned to the intervention group (IG) or the control group (CG). The IG attended a nurse-led DC program. The primary outcome was congruence between the participants' preferred and actual roles in decision-making. The secondary outcomes were an active role, satisfaction, decisional conflict, and knowledge. The follow-up questionnaires were administered at 12 weeks (T2) and 6 months (T3). RESULTS: Of the 413 women who were recruited, 389 returned the T1 questionnaires. At T2, the groups did not differ significantly in congruence between their preferred and actual roles in decision-making (0.12, 95% confidence interval [-0.03; 0.28], p = 0.128), with a slightly higher congruence in the CG. Women in both groups played a more active role at T2 than their stated preference at T1, with a notably higher percentage in the IG than the CG (IG: 40%, CG: 24.4% [-25.1; -6.1]). IG participants were more satisfied with their role and had less decisional conflict and greater knowledge. CONCLUSION: This DC program can help women who are carriers of BRCA1/2 PV participate actively in decision-making with regard to preventive measures.

Update Breast Cancer 2024 Part 1 - Expert Opinion on Advanced Breast Cancer.

Clinical evidence is interpreted based on clinical studies and personal experience which can lead to different interpretations of data. This makes the opinions issued by panels of experts such as the Advanced Breast Cancer Panel which convened in November 2023 for the seventh time (ABC7) particularly important. At the conference, current issues around advanced breast cancer were evaluated by an international team of experts. In 2023 the data on CDK4/6 inhibitors was so extensive that the answers to questions about the sequencing of therapy and the potential use of chemotherapy as an alternative therapy were relatively clear. Moreover, data on antibody drug conjugates which provides a good overview of their uses is available for all molecular subtypes. Some therapeutic settings, including patients with brain metastases or leptomeningeal disease, older patients, locally advanced breast cancer and visceral crises, continue to be particularly important and were discussed in structured sessions. The scientific context of some of the topics discussed at ABC7 is presented and assessed here.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2024.

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024. Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2024.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.