Health utility values of breast cancer treatments and the impact of varying quality of life assumptions on cost-effectiveness.

In breast cancer research, utility assumptions are outdated and inconsistent which may affect the results of quality adjusted life year (QALY) calculations and thereby cost-effectiveness analyses (CEAs). Four hundred sixty four female patients with breast cancer treated at Erasmus MC, the Netherlands, completed EQ-5D-5L questionnaires from diagnosis throughout their treatment. Average utilities were calculated stratified by age and treatment. These utilities were applied in CEAs analysing 920 breast cancer screening policies differing in eligible ages and screening interval simulated by the MISCAN-Breast microsimulation model, using a willingness-to-pay threshold of €20,000. The CEAs included varying sets on normative, breast cancer treatment and screening and follow-up utilities. Efficiency frontiers were compared to assess the impact of the utility sets. The calculated average patient utilities were reduced at breast cancer diagnosis and 6 months after surgery and increased toward normative utilities 12 months after surgery. When using normative utility values of 1 in CEAs, QALYs were overestimated compared to using average gender and age-specific values. Only small differences in QALYs gained were seen when varying treatment utilities in CEAs. The CEAs varying screening and follow-up utilities showed only small changes in QALYs gained and the efficiency frontier. Throughout all variations in utility sets, the optimal strategy remained robust; biennial for ages 40-76 years and occasionally biennial 40-74 years. In sum, we recommend to use gender and age stratified normative utilities in CEAs, and patient-based breast cancer utilities stratified by age and treatment or disease stage. Furthermore, despite varying utilities, the optimal screening scenario seems very robust.

Prognostic effect of nodal status before and after neoadjuvant chemotherapy in breast cancer: a Dutch population-based study.

PURPOSE: In breast cancer, neoadjuvant chemotherapy (NAC) can downstage the nodal status, and can even result in a pathological complete response, which is associated with improved prognosis. This study aimed to determine the prognostic effect of nodal status before and after NAC. METHODS: Women with breast cancer treated with NAC were selected from the Netherlands Cancer Registry if diagnosed between 2005 and 2019, and classified based on nodal status before NAC: node-negative (cN0), or node-positive based on fine needle aspiration cytology or core needle biopsy (cN+). Subgroups were based on nodal status after NAC: absence (ypN0) or presence (ypN+) of nodal disease. Five-year overall survival (OS) was assessed with Kaplan-Meier survival analyses, also per breast cancer molecular subtype. To adjust for potential confounders, multivariable analyses were performed. RESULTS: A total of 6,580 patients were included in the cN0 group, and 11,878 in the cN+ group. The 5-year OS of the cN0ypN0-subgroup was statistically significant better than that of the cN+ypN0-subgroup (94.4% versus 90.1%, p < 0.0001). In cN0 as well as cN+ disease, ypN+ had a statistically significant worse 5-year OS compared to ypN0. For hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)-, HR+ HER2+, HR-HER2+, and triple negative disease, respectively, 5-year OS in the cN0ypN+-subgroup was 89.7%, 90.4%, 73.7%, and 53.6%, and in the cN+ypN+-subgroup 84.7%, 83.2%, 61.4%, and 48.8%. In multivariable analyses, cN+ and ypN+ disease were both associated with worse OS. CONCLUSION: This study suggests that both cN-status and ypN-status, and molecular subtype should be considered to further improve prognostication.

Systematic review of targeted axillary dissection in node-positive breast cancer treated with neoadjuvant systemic therapy: variation in type of marker and timing of placement.

BACKGROUND: In node-positive (cN+) breast cancer treated with neoadjuvant systemic therapy, combining sentinel lymph node biopsy and targeted lymph node excision, that is targeted axillary dissection, increases accuracy. Targeted axillary dissection procedures differ in terms of the targeted lymph node excision technique. This systematic review aimed to provide an overview of targeted axillary dissection procedures regarding definitive marker type and timing of placement: before neoadjuvant systemic therapy (1-step procedure) or after neoadjuvant systemic therapy adjacent to a clip placed before the neoadjuvant therapy (2-step procedure). METHODS: PubMed and Embase were searched, to 4 July 2023, for RCTs, cohort studies, and case-control studies with at least 25 patients. Studies of targeted lymph node excision only (without sentinel lymph node biopsy), or where intraoperative localization of the targeted lymph node was not attempted, were excluded. For qualitative synthesis, studies were grouped by definitive marker and timing of placement. The targeted lymph node identification rate was reported. Study quality was assessed using a National Institutes of Health quality assessment tool. RESULTS: Of 277 unique records, 51 studies with a total of 4512 patients were included. Six definitive markers were identified: wire, 125I-labelled seed, 99mTc, (electro)magnetic/radiofrequency markers, black ink, and a clip. Fifteen studies evaluated one-step procedures, with the identification rate of the targeted lymph node at surgery varying from 8 of 13 to 47 of 47. Forty-one studies evaluated two-step procedures, with the identification rate of the clipped targeted lymph node on imaging after neoadjuvant systemic therapy varying from 49 to 100%, and the identification rate of the targeted lymph node at surgery from 17 of 24 to 100%. Most studies (40 of 51) were rated as being of fair quality. CONCLUSION: Various targeted axillary dissection procedures are used in clinical practice. Owing to study heterogeneity, the optimal targeted lymph node excision technique in terms of identification rate and feasibility could not be determined. Two-step procedures are at risk of not identifying the clipped targeted lymph node on imaging after neoadjuvant systemic therapy.

Facilitators and Barriers in the Implementation and Adoption of Patient-Reported Outcomes Measurements in Daily Practice.

OBJECTIVES: At the Erasmus Medical Center, patient-reported outcomes measures (PROMs) are implemented on a hospital-wide scale. However, less than half of the patients and healthcare professionals (HCPs) use these PROMs. Therefore, this study aimed to investigate facilitators and barriers for adoption of PROMs to develop guidance around implementation. METHODS: A mixed-methods study with a combination of interviews and focus groups and questionnaires was conducted, involving patients, both PROM nonresponders and PROM responders, HCPs, and medicine students and nurse specialists in training (hereafter "students"). Interview transcripts were subjected to thematic content analysis. Subsequently, questionnaires were developed and presented to all stakeholders to validate the findings. Finally, identified themes and implementation recommendations were presented in a final questionnaire to the Value-Based Healthcare Erasmus Medical Center expert group to prioritize findings. RESULTS: Interviews were conducted with 15 patients, 14 HCPs and 4 students, and 2 focus groups with 5 students. The questionnaire was completed by 370 of 999 responders (37.0%), 173 of 1395 nonresponders (12.5%), and 44 of 194 HCPs (22.7%), and 40 students were reached via an open link. The identified facilitators and barriers were grouped into 4 overarching themes: training on PROMs at different levels in the education of (future) HCPs, motivate and reduce the burden for the HCP, implement generic and disease-specific PROMs simultaneously, and motivate, activate, and reduce the patient burden. CONCLUSIONS: Providing end users with digital tools, implementation support, and a clear hospital-wide vision is important, yet this does not guarantee successful adoption of PROMs. Successful adoption necessitates ongoing efforts to engage, motivate, and train end users.

Let's talk about sex! Why should healthcare professionals address sexual distress in breast cancer patients and survivors?

PURPOSE: Sexual distress impacts the quality of life (QoL) of breast cancer patients but is often overlooked in standard care pathways. This study evaluated the prevalence and factors of sexual distress among Dutch breast cancer patients, compared them to the general population, and explored how sexual distress is discussed in clinical settings from the perspectives of patients and healthcare professionals (HCPs). METHODS: Questionnaires containing the Female Sexual Distress Scale (FSDS) and demographic variables were distributed to women with breast cancer. The effect of breast cancer on sexual distress was assessed with a Mann-Whitney U test. Multivariable linear regression was used to analyze variables associated with FSDS. The Sexuality Attitudes and Beliefs Survey (SABS) was sent to HCPs. RESULTS: Breast cancer patients reported significantly higher sexual distress compared to a Dutch non-breast cancer cohort, respectively 16.38 (SD 11.81) and 23.35 (SD 11.39). Factors associated with higher sexual distress were psychological comorbidities, the body image scale, and being diagnosed >10 years ago. Sexual distress was not discussed as often as patients needed. Barriers to addressing sexual distress were time constraints, HCPs' confidence in their ability to address sexual distress, and uncertainty about who is responsible for initiation. CONCLUSIONS: Breast cancer patients showed significantly higher sexual distress compared to the Dutch population. However, it was not frequently addressed in the consultation room. While some barriers have been identified, this study highlights the importance of further exploring obstacles to integrating discussions about sexual distress into routine care to improve QoL of breast cancer patients.

Internal Responsiveness of EQ-5D-5L and EORTC QLQ-C30 in Dutch Breast Cancer Patients during the First Year Post-Surgery: A Longitudinal Cohort Study.

The EuroQoL 5-Dimension 5-Level questionnaire (EQ-5D-5L) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) are commonly used Patient-Reported Outcome Measures (PROMs) for breast cancer. This study assesses and compares the internal responsiveness of the EQ-5D-5L and EORTC QLQ-C30 in Dutch breast cancer patients during the first year post-surgery. Women diagnosed with breast cancer who completed the EQ-5D-5L and EORTC QLQ-C30 pre-operatively (T0), 6 months (T6), and 12 months post-surgery (T12) were included. Mean differences of the EQ-5D-5L and EORTC QLQ-C30 between baseline and 6 months (delta 1) and between baseline and 12 months post-surgery (delta 2) were calculated and compared against the respective minimal clinically important differences (MCIDs) of 0.08 and 5. Internal responsiveness was assessed using effect sizes (ES) and standardized response means (SRM) for both deltas. In total, 333 breast cancer patients were included. Delta 1 and delta 2 for the EQ-5D-5L index and most scales of the EORTC QLQ-C30 were below the MCID. The internal responsiveness for both PROMs was small (ES and SRM < 0.5), with greater internal responsiveness for delta 1 compared to delta 2. The EQ-5D-5L index showed greater internal responsiveness than the EORTC QLQ-C30 Global Quality of Life scale and summary score. These findings are valuable for the interpretation of both PROMs in Dutch breast cancer research and clinical care.

Recurrence of breast cancer after reconstruction with macro-textured silicone breast implants: A retrospective cohort study.

BACKGROUND: Recently, old concerns linking silicone breast implants (SBIs) with breast cancer have resurfaced. These concerns apply specifically to the risk of breast cancer recurrence in patients who received breast reconstructions with macro-textured SBIs. In this study, we investigated the effect of breast reconstruction with macro-textured SBIs on long-term oncologic outcomes of breast cancer patients. MATERIALS AND METHODS: We conducted a retrospective cohort study in two large cancer centres in the Netherlands. Patients who had been treated for primary breast cancer between January 1st 2000 and December 31st 2015 were included. Data on treatment and oncologic outcomes were obtained from prospectively maintained institutional and nationwide registries. Patient files were reviewed manually to complement missing information. Missing data was accounted for by multiple imputation by chained equations (MICE). Reconstruction with a macro-textured SBI was analysed as a time-dependent variable. The main outcomes of interest were locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Hazard Ratios (HRs) were estimated using multivariable Cox proportional hazard models. RESULTS: Of the 4,695 women who were eligible for inclusion, 2,393 had undergone mastectomy. Of these women, 1,187 (25%) had received breast reconstruction with a macro-textured SBI. Mean follow-up time was 11.5 (SD, 5.0) years. Compared with women who had undergone a simple mastectomy or autologous breast reconstruction, women with an implant-based reconstruction did not differ significantly in LRRFS or DMFS after accounting for various confounding factors (HR 1.27 [95% CI 0.93 - 1.72] and HR 0.94 [95% CI 0.74 - 1.20], respectively). Sensitivity analysis in complete cases of patients and varies subgroup analyses yielded similar results. CONCLUSION: Reassuringly, in this multi-centre cohort study no difference was found in long-term oncologic outcomes between women who had received breast reconstruction with a macro-textured SBI and women who had undergone a simple mastectomy or autologous breast reconstruction.