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In breast cancer research, utility assumptions are outdated and inconsistent which may affect the results of quality adjusted life year (QALY) calculations and thereby cost-effectiveness analyses (CEAs).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.

Sexual well-being in patients with early-stage breast cancer at 1- and 2-year follow-up.

BACKGROUND: Sexual well-being (SWB) is an important aspect of overall quality of life and should therefore be considered when measuring the effect of breast cancer on daily life. AIM: To identify positive and negative predictive factors associated with change in SWB 1 year after diagnosis (T12; hereafter, ∆SWB) and whether SWB changes the year after. METHODS: All data were derived from an online patient-reported outcome measure that included patients aged >18 years who were treated for breast cancer between October 2015 and March 2022 at the Erasmus University Medical Center. Multivariable linear regression was used to analyze the association between demographic- and disease-specific variables and change in SWB between time of diagnoses (T0) and one year after (T12) (∆SWB). For defining the clinical relevance of ∆SWB, patients were divided into 3 groups based on their SWB score at T12: decreased, stable, and improved. Wilcoxon signed rank test was used to test the difference in SWB between T12 and T24 (2 years after diagnosis) in all 3 groups. OUTCOMES: Outcomes included the associations between demographic- and disease-specific variables and ∆SWB (T0 vs T12) and change in SWB the year after (T12 vs T24). RESULTS: An overall 204 patients were included, with a mean age of 51.7 years (SD, 12.8) and a mean SWB score of 64.3 (SD, 20.9) at T0. Body mass index >30 kg/m2 at T0 had a significant negative association (ß = -8.369, P = .019) with ∆SWB. Reconstruction (ß = 20.136, P < .001) and mastectomy (ß = 11.157, P < .001) had a significant positive association with ∆SWB vs lumpectomy. Change in psychological well-being had a significant positive relation to ∆SWB (ß = 0.349, P < .001). Patients with decreased SWB at T12 did not improve the year after (P = .376). CLINICAL IMPLICATIONS: By identifying the variables that are associated with decreased SWB during the trajectory of breast cancer treatment and by defining the clinical relevance of decreased SWB, patient groups can be targeted and offered extra support. STRENGTHS AND LIMITATIONS: This study is one of the first to analyze the development of SWB, instead of sexual function, over time in patients with breast cancer, and it uses data over a longer period. However, only one-third of the patients responded to the SWB domains at both time points. CONCLUSION: Type of operation, body mass index >30, and change in psychological well-being were associated with ∆SWB. Patients with decreased SWB 1 year after diagnosis tended not to improve or normalize the year after, indicating that intervention is needed to restore SWB in this specific group.

Health-related Quality of Life using the EQ-5D-5L: normative utility scores in a Dutch female population.

PURPOSE: Normative utility scores represent the health related quality of life of the general population, are of utmost importance in cost-effectiveness studies and should reflect relevant sexes and age groups. The aim of this study was to estimate EQ-5D-5L normative utility scores in a population of Dutch females, stratified by age, and to compare these scores to those of female populations of three other countries. METHODS: Dutch women completed the EQ-5D-5L online between January and July 2020. Mean normative utilities were computed using the Dutch EQ-5D-5L value set, stratified by age, tested for differences using the Kruskall-Wallis test, and compared to normative utility scores of female populations elsewhere. Additionally, to support the use of the Dutch EQ-5D-5L data in other settings, normative utility scores were also calculated by applying the value sets of Germany, United Kingdom and USA. RESULTS: Data of 9037 women were analyzed and the weighted mean utility score was 0.911 (SD 0.155, 95% CI 0.908-0.914). The mean normative utility scores differed between age groups, showing lower scores in older females. Compared to other normative utility scores of female populations, Dutch mean utilities were consistently higher except for age groups 18-24 and 25-34. With the three country-specific value sets, new age-specific mean normative utility scores were provided. CONCLUSION: This study provides mean normative utility scores of a large cohort of Dutch females per age group, which were found to be lower in older age groups. Utility scores calculated with three other value sets were made available.

Quality of life of caregivers of breast cancer patients: a cross-sectional evaluation.

BACKGROUND: The aim of this study was to evaluate the care-related quality of life in caregivers of breast cancer patients, to assess its association with breast cancer patients' health-related quality of life (HRQoL), and to identify its potential predictors. METHODS: Caregivers of breast cancer patients at six and twelve months follow up were identified through the institutes electronic patient reported outcome measurement collection tool. The Care-related Quality of Life Instrument (CarerQoL) was used to obtain CarerQoL utility scores by applying a pre-existent set of Dutch tariffs and the CarerQoL VAS score, which represented the overall happiness of caregivers. The associations between breast cancer patients' EQ-5D-5L and EORTC QLQ-C30 scores and caregivers' CarerQoL scores was determined with Spearman's correlation coefficients. Associations between log transformed CarerQol scores and patient and caregiver characteristics were analyzed with multivariable linear regression analyses. RESULTS: A total of 116 completed CarerQoL questionnaires were analyzed. Most caregivers were male spouses or partners (81.4%) with a mean age of 55.7 ± 16.4. The median CarerQoL utility score was 92.4/100 and median CarerQoL VAS was 8.0/10. We found weak correlations between CarerQoL VAS scores and patients' EQ-5D-5L utility score (0.301, p = 0.002) and EQ VAS score (0.251, p = 0.009), and between EORTC QLQ-C30 scores and CarerQol VAS (0.339, p < 0.001) and utility score (0.236, p = 0.015). There was a negative association between chemotherapy and log-transformed CarerQoL utility score (B = - 0.063, p = 0.001) and VAS score (B = - 0.044, p = 0.038) at six months follow-up. CONCLUSIONS: This study provides the first evaluation of the CarerQoL in caregivers of Dutch breast cancer patients. Caregivers' happiness was associated with breast cancer patients' HRQoL. Our results can be used as reference values for future care-related quality of life evaluations. Breast cancer patients face many difficulties during their cancer journey and often need the support of their caregivers. Despite the fact that successfully providing informal care can have positive effects on caregivers' wellbeing, it may also have a negative impact on their quality of life. Monitoring the quality of life using a standardized questionnaire, such as the CarerQoL questionnaire, may result in early detection of possible quality of life issues. In this study, we evaluated 116 caregivers and found overall high CarerQoL scores. The scores showed a positive relation to the patients' quality of life. Lower CarerQoL scores at six months after surgery were found in caregivers of patients who received chemotherapy. Our research underlines the importance to include caregivers of breast cancer patients in clinical practice, provides reference values for future research, and the results can be used to manage the caregivers' expectations prior to treatment.

Bilateral prophylactic mastectomy: should we preserve the pectoral fascia? Protocol of a Dutch double blinded, prospective, randomised controlled pilot study with a within-subject design (PROFAS).

INTRODUCTION: Bilateral prophylactic mastectomy (BPM) in women with a high risk of developing breast cancer has shown to provide the greatest risk reduction. Many surgical guidelines recommend the removal of the pectoral fascia (PF) in mastectomies; however, there is no evidence to support this statement. Reported wound-related complications following mastectomy include seroma, flap necrosis, infection and haematoma. Seroma causes discomfort and may delay the reconstructive procedures. Whether removal or preservation of the PF influences drain volume, seroma formation and other postoperative complications following BPM remains unclear. The aim of this study is to assess the impact of removal versus preservation of the PF on drain policy and seroma after BPM. METHODS AND ANALYSIS: This is a double blinded, prospective, randomised controlled pilot study with a within-subject design. The inclusion criteria are women >18 years, presenting in the Academic Breast Cancer Centre Rotterdam, who are opting for BPM. Patients with a history or diagnosis of breast cancer are excluded. According to the sample size calculation based on the difference in total drain volume, a number of 21 eligible patients will be included. Randomisation will occur within the patient, which means PF preservation in one breast and PF removal in the contralateral breast. The primary study endpoint is total drainage volume. Secondary study outcomes include time to drain removal, number of needle aspirations, postoperative complications and length of hospital stay. ETHICS AND DISSEMINATION: The study is approved by the Erasmus Medical Center Review Board (REC 2020-0431). Results will be presented during international conferences and published in a peer-reviewed academic journal. TRIAL REGISTRATION NUMBER: NCT05391763; clinicaltrials.gov.

What affects women's decision-making on breast reconstruction after mastectomy for breast cancer?

PURPOSE: To establish the breast reconstruction rate in a large Dutch teaching hospital, and to gain insight into the motives of women to opt for or reject post-mastectomy breast reconstruction. METHODS: In a retrospective, cross-sectional study, all consecutive patients who underwent mastectomy for invasive breast cancer or ductal carcinoma in situ (DCIS) were identified and categorized into two groups based on subsequent breast reconstruction or not. Patient-reported outcomes were assessed with the validated Breast-Q and a short survey about the decision-making process in breast reconstruction. These outcomes were compared between the two groups using univariable analyses, multivariable logistic regression, and multiple linear regression analyses. The Breast-Q scores were also compared to Dutch normative values. RESULTS: A total of 319 patients were identified of whom 68% had no breast reconstruction. Of the 102 patients with breast reconstruction, the majority (93%) received immediate, instead of delayed breast reconstruction. The survey was completed by 155 (49%) patients. The non-reconstruction group, on average, reported significantly poorer psychosocial well-being, compared to the reconstruction group as well as compared to the normative data. However, the majority of the non-reconstruction group (83%) stated that they had no desire for breast reconstruction. In both groups, most patients stated that the provided information was sufficient. CONCLUSION: Patients have personal motives to opt for or reject breast reconstruction. It seemed that patients differ in their rating of values that affect their decision since the same arguments were used to opt for or reject reconstruction. Notably, patients were well-informed in their decision making.

Quality of Life and Complications after Nipple- versus Skin-Sparing Mastectomy followed by Immediate Breast Reconstruction: A Systematic Review and Meta-Analysis.

BACKGROUND: Nipple-sparing mastectomy (NSM) has emerged as an alternative procedure for skin-sparing mastectomy (SSM), followed by immediate breast reconstruction. Because oncologic safety appears similar, patient-reported outcomes (PROs) and complication risks may guide decision-making in individual patients. Therefore, the aim of this systematic review was to compare PROs and complication rates after NSM and SSM. METHODS: A systematic literature review evaluating NSM versus SSM was performed using the Embase, MEDLINE, and Cochrane databases. Methodologic quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. Primary outcomes were PROs and complications. Studies that evaluated BREAST-Q scores were used to perform meta-analyses on five BREAST-Q domains. RESULTS: Thirteen comparative studies including 3895 patients were selected from 1202 articles found. Meta-analyses of the BREAST-Q domains showed a significant mean difference of 7.64 in the Sexual Well-being domain ( P = 0.01) and 4.71 in the Psychosocial Well-being domain ( P = 0.03), both in favor of NSM. Using the specifically designed questionnaires, no differences in overall satisfaction scores were found. There were no differences in overall complication rates between the two groups. CONCLUSIONS: Patient satisfaction scores were high after both NSM and SSM; however, NSM led to a higher sexual and psychosocial well-being. No differences in complication rates were found. In combination with other factors, such as oncologic treatments, complication risk profile, and fear of cancer recurrence, the decision for NSM or SSM has to be made on an individual basis and only if NSM is considered to be oncologically safe.

BREAST-Q Breast-Conserving Therapy Module: Normative Data from a Dutch Sample of 9059 Women.

BACKGROUND: BREAST-Q, a patient-reported outcome measure for cosmetic and reconstructive breast surgery, is widely used in both clinical research and practice. The aim of this study was to acquire normative data of BREAST-Q's Breast-Conserving Therapy Module from a Dutch population sample and to compare it with existing normative BREAST-Q values. METHODS: Flyers with QR codes, WhatsApp, and one academic center's Facebook and LinkedIn platforms were used to direct participants to self-complete an online version of four domains of the preoperative BREAST-Q Breast-Conserving Therapy Module. BREAST-Q domain scores were log transformed to normalize the distribution. Univariable regression analyses were used to assess (nonlinear) associations between age and BREAST-Q domain scores. RESULTS: Overall, 9059 questionnaire responses were analyzed. Median (±SD) BREAST-Q domain scores were 64.0 ± 18.0 (satisfaction with breasts), 69.0 ± 21.0 (psychosocial well-being), 92.0 ± 20 (physical well-being), and 59.0 ± 15.0 (sexual well-being). Age as a linear term was associated with log-transformed satisfaction with breasts, psychosocial well-being, and physical well-being; sexual well-being was a quadratic function of age. Previous breast surgery unrelated to breast cancer was a significant predictor for higher log-transformed satisfaction with breasts (ß = 0.04, p < 0.001) and higher sexual well-being score (ß = -0.05, p < 0.001). Compared with previously published normative data, small differences were found in mean BREAST-Q domain scores (mean differences ranging between 2.45 and 6.24). CONCLUSIONS: Normative Dutch BREAST-Q scores follow similar patterns across domains in comparison with previously published normative data. Normative Dutch BREAST-Q data enable future comparisons in breast-related satisfaction and quality of life issues of Dutch patients with breast cancer compared with their age-matched peers.

Measuring Quality of Life Using Patient-Reported Outcomes in Real-World Metastatic Breast Cancer Patients: The Need for a Standardized Approach.

Metastatic breast cancer (MBC) patients are almost always treated to minimize the symptom burden, and to prolong life without a curative intent. Although the prognosis of MBC patients has improved in recent years, the median survival after diagnosis is still only 3 years. Therefore, the health-related quality of life (HRQoL) should play a leading role in making treatment decisions. Heterogeneity in questionnaires used to evaluate the HRQoL in MBC patients complicates the interpretability and comparability of patient-reported outcomes (PROs) globally. In this review, we aimed to provide an overview of PRO instruments used in real-world MBC patients and to discuss important issues in measuring HRQoL. Routinely collecting symptom information using PROs could enhance treatment evaluation and shared decision-making. Standardizing these measures might help to improve the implementation of PROs, and facilitates collecting and sharing data to establish valid comparisons in research. This is a prerequisite to learn about how they could impact the clinical care pathway. In addition, the prognostic value of intensified PRO collection throughout therapy on survival and disease progression is promising. Future perspectives in the field of PROs and MBC are described.