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.

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.

European quality indicators developed by the European Commission Initiative on Breast Cancer: a first nationwide assessment for the Dutch setting.

PURPOSE: This observational study aims to assess the feasibility of calculating indicators developed by the European Commission Initiative on Breast Cancer (ECIBC) for the Dutch breast cancer population. METHODS: Patients diagnosed with invasive or in situ breast cancer between 2012 and 2018 were selected from the Netherlands Cancer Registry (NCR). Outcomes of the quality indicators (QI) were presented as mean scores and were compared to a stated norm. Variation between hospitals was assessed by standard deviations and funnel plots and trends over time were evaluated. The quality indicator calculator (QIC) was validated by comparing these outcomes with the outcomes of constructed algorithms in Stata. RESULTS: In total, 133,527 patients were included. Data for 24 out of 26 QIs were available in the NCR. For 67% and 67% of the QIs, a mean score above the norm and low or medium hospital variation was observed, respectively. The proportion of patients undergoing a breast reconstruction or neoadjuvant systemic therapy increased over time. The proportion treated within 4 weeks from diagnosis, having >10 lymph nodes removed or estrogen negative breast cancer who underwent adjuvant chemotherapy decreased. The outcomes of the constructed algorithms in this study and the QIC showed 100% similarity. CONCLUSION: Data from the NCR could be used for the calculation of more than 92% of the ECIBC indicators. The quality of breast cancer care in the Netherlands is high, as more than half of the QIs already score above the norm and medium hospital variation was observed. The QIC can be easy and reliably applied.

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.

Patient-Reported Outcome Measures to Improve the Care Continuum for Patients With Metastatic Breast Cancer: Opportunities and Implications for Nursing Practice.

OBJECTIVES: Albeit treatable, metastatic breast cancer (MBC) remains incurable. To achieve remaining life years lived well, extended survival should be balanced with optimal health-related quality of life (HRQoL) and timely initiated supportive, palliative, and end-of-life care. The Advanced Breast Cancer (ABC) Global Alliance identified 10 urgent and actionable goals for the decade between 2015 and 2025 to achieve substantial improvement in the lives of patients living with ABC, including MBC. Enhancements are needed for HRQoL, research, quality of care, and survival. We explore the potential of patient-reported outcome measures (PROMs) in addressing these gaps and aim to describe opportunities and current initiatives for improving the MBC care continuum through PROMs. DATA SOURCES: Narrative description of recent literature on MBC and PROMs. CONCLUSION: We believe PROMs can make valuable contributions to seven of the 10 goals described: 1) enhancing the understanding of MBC through high-quality data collection, 2) improving HRQoL and raising consideration of survival versus HRQoL, 2) prolonging survival, 4) increasing referral to nonclinical support services, 5) supporting patient-healthcare provider communication, 6) encouraging improvements in healthcare access, and 7) supporting meeting patients' informational needs. IMPLICATIONS FOR NURSING PRACTICE: Maximizing the benefits of PROMs requires effective implementation. Because nurses and nurse practitioners are at the forefront of care, they can offer a comprehensive understanding of patients' needs and play a crucial role in facilitating the integration of PROMs into routine care for MBC patients and ultimately optimizing patients' outcomes and life years and months left.

Proof-of-concept study linking ex vivo sensitivity testing to neoadjuvant anthracycline-based chemotherapy response in breast cancer patients.

We developed a functional ex vivo anthracycline-based sensitivity test. Surgical resection material of primary breast cancer (BC) was used to determine criteria for the ex vivo sensitivity assay based on morphology, proliferation and apoptosis. Subsequently, a proof-of-concept study was performed correlating results of this assay on primary BC biopsies with in vivo response after treatment with anthracycline-containing neoadjuvant chemotherapy (NAC). Cut off values for the ex vivo anthracycline-based sensitivity test were established based on analysis of 21 primary breast tumor samples obtained after surgery. In the proof-of-concept study based on a new set of tumor biopsies, 41 patients were included. Eight biopsies did not contain tumor cells and three patients could not be biopsied for various reasons. In the remaining 30 biopsies, the success rate of the ex vivo test was 77% (23/30); six out of seven failed tests were due to excessive apoptosis, our pre-specified test criteria. Of the 23 patients with a successful ex vivo test result, three patients did not undergo NAC after the biopsy. Here we report the ex vivo anthracycline-based sensitivity assay is feasible on biopsy material and shows 75% concordance between ex vivo outcomes and in vivo MRI response. Unfortunately, the percentage of unsuccessful tests is rather high. This study provides the foundation for further development of ex vivo sensitivity assays.

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.

Comparing quality of breast cancer care in the Netherlands and Norway by federated propensity score analytics.

PURPOSE: The aim of the study was to benchmark and compare breast cancer care quality indicators (QIs) between Norway and the Netherlands using federated analytics preventing transfer of patient-level data. METHODS: Breast cancer patients (2017-2018) were retrieved from the Netherlands Cancer Registry and the Cancer Registry of Norway. Five European Society of Breast Cancer Specialists (EUSOMA) QIs were assessed: two on magnetic resonance imaging (MRI), two on surgical approaches, and one on postoperative radiotherapy. The QI outcomes were calculated using 'Vantage 6' federated Propensity Score Stratification (PSS). Likelihood of receiving a treatment was expressed in odds ratios (OR). RESULTS: In total, 39,163 patients were included (32,786 from the Netherlands and 6377 from Norway). PSS scores were comparable to the crude outcomes of the QIs. The Netherlands scored higher on the QI 'proportions of patients preoperatively examined with breast MRI' [37% vs.17.5%; OR 2.8 (95% CI 2.7-2.9)], the 'proportions of patients receiving primary systemic therapy examined with breast MRI' [83.3% vs. 70.8%; OR 2.3 (95% CI 1.3-3.3)], and 'proportion of patients receiving a single breast operation' [95.2% vs. 91.5%; OR 1.8 (95% CI 1.4-2.2)]. Country scores for 'immediate breast reconstruction' and 'postoperative radiotherapy after breast-conserving surgery' were comparable. The EUSOMA standard was achieved in both countries for 4/5 indicators. CONCLUSION: Both countries achieved high scores on the QIs. Differences were observed in the use of MRI and proportion of patients receiving single surgery. The federated approach supports future possibilities on benchmark QIs without transfer of privacy-sensitive data.

Risk-adjusted benchmarking of long-term overall survival in patients with HER2-positive early-stage Breast cancer: A Swedish retrospective cohort study.

AIM: The main objective of the current study was to explore the value of risk-adjustment when comparing (i.e. benchmarking) long-term overall survival (OS) in breast cancer (BC) between Swedish regions. We performed risk-adjusted benchmarking of 5- and 10-year OS after HER2-positive early BC diagnosis between Sweden's two largest healthcare regions, constituting approximately a third of the total population in Sweden. METHODS: All patients diagnosed with HER2-positive early-stage BC between 01-01-2009 and 31-12-2016 in healthcare regions Stockholm-Gotland and Skane were included in the study. Cox proportional hazards model was used for risk-adjustment. Unadjusted (i.e. crude) and adjusted 5- and 10-year OS was benchmarked between the two regions. RESULTS: The crude 5-year OS was 90.3% in the Stockholm-Gotland region and 87.8% in the Skane region. The crude 10-year OS was 81.7% in the Stockholm-Gotland region and 77.3% in the Skane region. However, when adjusted for age, menopausal status and tumour biology, there was no significant OS disparity between the regions, neither at the 5-year nor 10-year follow-up. CONCLUSION: This study showed that risk-adjustment is relevant when benchmarking OS in BC, even when comparing regions from the same country that share the same national treatment guidelines. This is, to our knowledge, the first published risk-adjusted benchmarking of OS in HER2-positive BC.

Dutch normative data of the sexual distress scale and the body image scale.

PURPOSE: Sexual health is an important contributing factor for health-related quality of life, but research in this domain is scarce. Moreover, normative data are needed to interpret patient-reported outcome measures on sexual health. The aim of this study was to collect and describe normative scores of the Female Sexual Distress Scale (FSDS) and the Body Image Scale (BIS) from the Dutch population and assess the effect of important demographic and clinical variables on the outcome. As the FSDS is also validated in men, we refer to it as SDS. METHOD: Dutch respondents completed the SDS and BIS between May and August 2022. Sexual distress was defined as a SDS score > 15. Descriptive statistics were calculated to present normative data per age group per gender after post-stratification weighting was applied. Multiple logistic and linear regression analyses were conducted to assess the effect of age, gender, education, relationship status, history of cancer and (psychological) comorbidities on SDS and BIS. RESULTS: For the SDS 768 respondents were included with a weighted mean score of 14.41 (SD 10.98). Being female (OR 1.77, 95% CI [1.32; 2.39]), having a low educational level (OR 2.02, CI [1.37; 2.39]) and psychological comorbidities (OR: 4.86, 95% CI [2.17; 10.88]) were associated with sexual distress. For the BIS, 696 respondents were included. Female gender (ß: 2.63, 95% CI [2.13; 3.13]), psychological comorbidities (ß: 2.45, 95% CI [1.43; 3.47]), higher age (ß: -0.07, 95% CI [-0.09; -0.05]), and a high educational level (ß:-1.21, CI: -1.79 to -0.64) were associated with the non-disease related questions of the Body Image Scale. CONCLUSION: This study provides age- and gender-dependent normative values for the SDS and the non-disease related questions of the BIS. Sexual distress and body image are influenced by gender, education level, relationship status and psychological comorbidities. Moreover, age is positively associated with Body Image.

Surgical outcomes following breast reconstruction in patients with and without a history of chest radiotherapy for Hodgkin lymphoma: a multicentre, matched cohort study.

BACKGROUND: Breast cancer is the most common treatment-related second malignancy among women with previous chest radiotherapy for Hodgkin lymphoma (HL). Little is known about the effects of this kind of radiotherapy on the outcomes of postmastectomy breast reconstruction (BR). This study compared adverse outcomes of BR after HL-related chest radiotherapy to matched controls. METHODS: The authors conducted a retrospective, matched cohort study in two expert cancer centres in the Netherlands. BRs after therapeutic or prophylactic mastectomy in HL survivors who received chest radiotherapy were matched with BRs in nonirradiated patients without HL on age at mastectomy date, date of BR, and type of BR. The primary outcome was complication-related BR failure or conversion and secondary outcomes were complication-related re-operation, capsular contracture, major donor-site complications, and complication-related ICU admission. The authors analyzed all outcomes univariably using Fisher's exact tests and the authors assessed reconstruction failure, complication-related re-operation, and capsular contracture with multivariable Cox regression analysis adjusting for confounding and data clustering. RESULTS: Seventy BRs in 41 patients who received chest radiotherapy for HL were matched to 121 BRs in 110 nonirradiated patients. Reconstruction failure did not differ between HL survivors (12.9%) and controls (12.4%). The comparison groups showed no differences in number of reoperations, major donor-site complications, or capsular contractures. BR in HL survivors more often let to ICU admission due to complications compared with controls ( P =0.048). CONCLUSIONS: We observed no increased risk of adverse outcomes following BR after previous chest radiotherapy for HL. This is important information for counselling these patients and may improve shared decision-making.

The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions.

BACKGROUND: Implant-based breast reconstructions contribute considerably to the quality of life of breast cancer patients. A knowledge gap exists concerning the potential role of silicone breast implants in the development of so-called "breast implant illness" (BII) and autoimmune diseases in breast cancer survivors with implant-based reconstructions. BII is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. METHODS: The Areola study is a multicenter retrospective cohort study with prospective follow-up aiming to assess the risk of BII and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. In this report, we set out the rationale, study design, and methodology of this cohort study. The cohort consists of breast cancer survivors who received surgical treatment with implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As a comparison group, a frequency-matched sample of breast cancer survivors without breast implants will be selected. An additional group of women who received breast augmentation surgery in the same years will be selected to compare their characteristics and health outcomes with those of breast cancer patients with implants. All women who are still alive will be invited to complete a web-based questionnaire covering health-related topics. The entire cohort including deceased women will be linked to population-based databases of Statistics Netherlands. These include a registry of hospital diagnostic codes, a medicines prescription registry, and a cause-of-death registry, through which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and autoimmune diseases. In addition, risk factors for the development of BII and autoimmune disorders will be assessed among women with implants. DISCUSSION: The Areola study will contribute to the availability of reliable information on the risks of BII and autoimmune diseases in Dutch breast cancer survivors with silicone breast implants. This will inform breast cancer survivors and aid future breast cancer patients and their treating physicians to make informed decisions about reconstructive strategies after mastectomy. REGISTRATION: This study is registered at ClinicalTrials.gov on June 2, 2022 (NCT05400954).

Trends in emotional functioning and psychosocial wellbeing in breast cancer survivors: a prospective cohort study using patient-reported outcome measures.

BACKGROUND: A breast cancer diagnosis can threaten every aspect of a woman's wellbeing, including her mental health. With the growing number of breast cancer survivors, studies addressing mental health in this population are of increasing importance now more than ever. Therefore, the current study investigated trends in emotional functioning and psychosocial wellbeing of breast cancer survivors, and the demographic and treatment characteristics that may influence these trends. METHODS: Prospectively collected data of women treated for breast cancer at the Erasmus MC were analyzed in this study using a cohort study design. Emotional functioning was measured using the EORTC-QLQ-C30, while psychosocial wellbeing was measured using the BREAST-Q. Type of surgery, age, family status and employment status of study participants were retrieved, and multilevel analyses were performed to identify trends in emotional functioning and psychosocial wellbeing and to determine the relationship between aforementioned characteristics and these outcomes. RESULTS: Three hundred thirty-four cancer survivors were analyzed. Psychosocial wellbeing declined, but emotional functioning showed a steady improvement over time. Women who underwent breast reconstruction showed a steeper increase in their emotional functioning, and women with no partner or children showed a marginal decline in psychosocial wellbeing between baseline and 12 months after surgery. CONCLUSIONS: These findings can be utilized by healthcare teams to identify breast cancer patients at risk for emotional problems and to provide adequate psychological support to those women who need help dealing with their emotions and self-concept in order to optimize clinical treatment.

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.

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.

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.

Changes in breast cancer treatment during the COVID-19 pandemic: a Dutch population-based study.

PURPOSE: We aimed to compare (1) treatments and time intervals between treatments of breast cancer patients diagnosed during and before the COVID-19 pandemic, and (2) the number of treatments started during and before the pandemic. METHODS: Women were selected from the Netherlands Cancer Registry. For aim one, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the treatment of women diagnosed within four periods of 2020: pre-COVID (weeks 1-8), transition (weeks 9-12), lockdown (weeks 13-17), and care restart (weeks 18-26), with data from 2018/2019 as reference. Wilcoxon rank-sums test was used to compare treatment intervals, using a two-sided p-value < 0.05. For aim two, number of treatments started per week in 2020 was compared with 2018/2019. RESULTS: We selected 34,097 women for aim one. Compared to 2018/2019, neo-adjuvant chemotherapy was less likely for stage I (OR 0.24, 95%CI 0.11-0.53), stage II (OR 0.63, 95%CI 0.47-0.86), and hormone receptor+/HER2- tumors (OR 0.55, 95%CI 0.41-0.75) diagnosed during transition. Time between diagnosis and first treatment decreased for patients diagnosed during lockdown with a stage I (p < 0.01), II (p < 0.01) or III tumor (p = 0.01). We selected 30,002 women for aim two. The number of neo-adjuvant endocrine therapies and surgeries starting in week 14, 2020, increased by 339% and 18%, respectively. The number of adjuvant chemotherapies decreased by 42% in week 15 and increased by 44% in week 22. CONCLUSION: The pandemic and subsequently altered treatment recommendations affected multiple aspects of the breast cancer treatment strategy and the number of treatments started per week.

Diagnostic Accuracy of Radioactive Iodine Seed Placement in the Axilla With Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer.

Importance: Several less-invasive staging procedures have been proposed to replace axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) in patients with initially clinically node-positive (cN+) breast cancer, but these procedures may fail to detect residual disease. Owing to the lack of high-level evidence, it is not yet clear which procedure is most optimal to replace ALND. Objective: To determine the diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS), a targeted axillary dissection procedure. Design, Setting, and Participants: This was a prospective, multicenter, noninferiority, diagnostic accuracy trial conducted from March 1, 2017, to December 31, 2019. Patients were included within 14 institutions (general, teaching, and academic) throughout the Netherlands. Patients with breast cancer clinical tumor categories 1 through 4 (cT1-4; tumor diameter <2 cm and up to >5 cm or extension to the chest wall or skin) and pathologically proven positive axillary lymph nodes (ie, clinical node categories cN1, metastases to movable ipsilateral level I and/or level II axillary nodes; cN2, metastases to fixed or matted ipsilateral level I and/or level II axillary nodes; cN3b, metastases to ipsilateral level I and/or level II axillary nodes with metastases to internal mammary nodes) who were treated with NAC were eligible for inclusion. Data were analyzed from July 2020 to December 2021. Intervention: Pre-NAC, the marking of a pathologically confirmed positive axillary lymph node with radioactive iodine seed (MARI) procedure, was performed and after NAC, sentinel lymph node biopsy (SLNB) combined with excision of the marked lymph node (ie, RISAS procedure) was performed, followed by ALND. Main Outcomes and Measures: The identification rate, false-negative rate (FNR), and negative predictive value (NPV) were calculated for all 3 procedures: RISAS, SLNB, and MARI. The noninferiority margin of the observed FNR was 6.25% for the RISAS procedure. Results: A total of 212 patients (median [range] age, 52 [22-77] years) who had cN+ breast cancer underwent the RISAS procedure and ALND. The identification rate of the RISAS procedure was 98.2% (223 of 227). The identification rates of SLNB and MARI were 86.4% (197 of 228) and 94.1% (224 of 238), respectively. FNR of the RISAS procedure was 3.5% (5 of 144; 90% CI, 1.38-7.16), and NPV was 92.8% (64 of 69; 90% CI, 85.37-97.10), compared with an FNR of 17.9% (22 of 123; 90% CI, 12.4%-24.5%) and NPV of 72.8% (59 of 81; 90% CI, 63.5%-80.8%) for SLNB and an FNR of 7.0% (10 of 143; 90% CI, 3.8%-11.6%) and NPV of 86.3% (63 of 73; 90% CI, 77.9%-92.4%) for the MARI procedure. In a subgroup of 174 patients in whom SLNB and the MARI procedure were successful and ALND was performed, FNR of the RISAS procedure was 2.5% (3 of 118; 90% CI, 0.7%-6.4%), compared with 18.6% (22 of 118; 90% CI, 13.0%-25.5%) for SLNB (P < .001) and 6.8% (8 of 118; 90% CI, 3.4%-11.9%) for the MARI procedure (P = .03). Conclusions and Relevance: Results of this diagnostic study suggest that the RISAS procedure was the most feasible and accurate less-invasive procedure for axillary staging after NAC in patients with cN+ breast cancer.

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.