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In breast cancer research, utility assumptions are outdated and inconsistent which may affect the results of quality adjusted life year (QALY) calculations and thereby cost-effectiveness analyses (CEAs).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

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 MC, Patient Reported Outcome Measures (PROMs) are implemented on a hospital-wide scale. However, less than half of the patients and healthcare professionals (HCP) utilize 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 non-responders and PROM responders, HCPs, and medicine students and nurse specialists in training (hereafter 'students'). (Group)interview transcripts were subjected to thematic content analysis. Subsequently, questionnaires were developed and presented to all stakeholders to validate the findings. Last, identified themes and implementation recommendations were presented in a final questionnaire to the Value Based Healthcare Erasmus MC 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 370/999 responders (37.0%), 173/1395 non-responders (12.5%), 44/194 HCPs (22.7%) and 40 students were reached via an open link. The identified facilitators and barriers were grouped into four 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 are important, yet this does not guarantee successful adoption of PROMs. Successful adoption necessitates ongoing efforts to engage, motivate and train end-users.

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.

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.

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.

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.

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.

Survival of BRCA1/BRCA2-associated pT1 breast cancer patients, a cohort study.

PURPOSE: Intensive screening in BRCA1/2 mutation carriers aims to improve breast cancer (BC) prognosis. Our aim is to clarify the prognostic impact of tumor size in BRCA mutation carriers with a pT1 BC, which is currently unclear. We are especially interested in differences between pT1a, pT1b, and pT1c regarding the prognosis of node-negative breast cancer, the effect of chemotherapy, and the prevalence of lymph node involvement. METHODS: For this study, BRCA1/2-associated BC patients were selected from a nationwide cohort. Primary outcomes were 10-year overall survival (OS) per pT1a-b-c group and the effect of chemotherapy on prognosis of node-negative BC, using Kaplan-Meier and Cox models. Finally, we evaluated lymph node involvement per pT1a-b-c group. RESULTS: 963 women with pT1 BRCA1/2-associated BC diagnosed between 1990 and 2017 were included, of which 679 had pN0 BC. After a median follow-up of 10.5 years, 10-year OS in patients without chemotherapy was 77.1% in pT1cN0 and lower than for pT1aN0 (91.4%, p = 0.119) and pT1bN0 (90.8%, p = 0.024). OS was better with than without chemotherapy for pT1cN0 (91.6% vs. 77.1%, p = 0.001; hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.21-1.48). Lymph node involvement was 24.9% in pT1c, 18.8% in pT1b, and 8.6% in pT1a. CONCLUSION: Smaller tumor size is associated with better OS and less lymph node involvement in pT1 BRCA1/2-associated BC patients. The results suggest that early detection in BRCA1/2 mutation carriers of pT1a/b BC may reduce mortality and the need for systemic therapy.

A descriptive systematic review of the relationship between personality traits and quality of life of women with non-metastatic breast cancer.

BACKGROUND: Quality of life (QoL) is an important patient-reported outcome that has been studied extensively as an endpoint. There is a growing interest in factors that may influence QoL, such as personality. This descriptive systematic review examined the relationship between personality and QoL in women with non-metastatic breast cancer.  METHODS: On November 24th, 2020, with a update on March 7th, 2022, PubMed, PsycINFO, CINAHL, Web of Science and Embase were systematically searched for studies that assessed the direct relationship between personality traits and QoL among adult women diagnosed with non-metastatic breast cancer. The National Institutes of Health Study Quality Assessment Tool was used to assess the quality and risk of bias of the included studies. Three reviewers independently extracted data regarding objectives, population, setting, design, method, outcome measurements and key results. The results are descriptively reported. RESULTS: Twelve studies (6 cohort studies and 6 cross-sectional studies) were included. Three studies were rated as poor, one study was rated as good, and the remaining studies were rated as moderate. There was a small to moderate effect of personality on QoL as correlation coefficients ranged from 0.10 to 0.77, and the explained variance ranged from 4 to 43%. The (strength of the) relationship depended on the personality trait and QoL domain that was measured and was most apparent for the personality traits 'optimism' and 'trait anxiety' on psychosocial QoL domains. The results for the personality traits (unmitigated) agency, agreeableness, conscientiousness, novelty seeking, and self-efficacy indicated a smaller but statistically significant correlation between these personality traits and QoL. CONCLUSIONS: The results confirm that personality affects QoL in women with non-metastatic breast cancer and thus provides evidence that personality traits are indeed important influential factors of QoL. It is therefore strongly recommended for all future QoL research to measure personality traits and use these variables as predictive factors, as they are needed to accurately interpret QoL. Information regarding personality traits provide physicians and patients with an interpretation of low or deterioration of QoL, which could guide physicians to improve their patients' health outcomes and subsequently QoL using psycho-oncological support or treatment.

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.

Patient-derived breast model repository, a tool for hyperthermia treatment planning and applicator design.

OBJECTIVE: The addition of hyperthermia in the treatment of intact breast cancer with the aim to improve local response is currently in a research phase. First, optimal hyperthermia devices need to be developed, for which a diverse, anatomically and pathologically accurate set of patient models is necessary. METHODS: To investigate the effects of inter-subject variations on hyperthermia treatment plans, we generated a repository of 22 anatomically and pathologically diverse patient models based on MR images of breast cancer patients. Hyperthermia treatment plans were generated for the 22 models using a generic theoretical phased array hyperthermia applicator. RESULTS: Good temperature coverage was achieved in the vast majority of the models, with median values for T10 = 43.5°C (41.9-43.8°C), T50 = 42.5°C (41.3-43.3°C), and T90 = 41.3°C (39.8-42.6°C) under the condition that the maximum temperature increase in the patient is limited to 44°C. CONCLUSIONS: For future development of hyperthermia devices and treatment methods, a repository with a sufficiently large number of representative patient models, such as the one provided in this study, should be used to ensure applicability to a wide variety of patients. This repository is therefore made publicly available.

Correction to: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.

After publication of the original article [1], we were notified that columns in Table 2 were erroneously displayed.

Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.

BACKGROUND: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. METHODS: A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. RESULTS: There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. CONCLUSION: We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.

A retrospective alternative for active surveillance trials for ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast is a nonobligate precursor of invasive breast cancer, accounting for 20 % of screen-detected breast cancers. Little is known about the natural progression of DCIS because most patients undergo surgery upon diagnosis. Many DCIS patients are likely being overtreated, as it is believed that only around 50 % of DCIS will progress to invasive carcinoma. Robust prognostic markers for progression to invasive carcinoma are lacking. In the past, studies have investigated women who developed a recurrence after breast-conserving surgery (BCS) and compared them with those who did not. However, where there is no recurrence, the patient has probably been adequately treated. The present narrative review advocates a new research strategy, wherein only those patients with a recurrence are studied. Approximately half of the recurrences are invasive cancers, and half are DCIS. So-called "recurrences" are probably most often the result of residual disease. The new approach allows us to ask: why did some residual DCIS evolve to invasive cancers and others not? This novel strategy compares the group of patients that developed in situ recurrence with the group of patients that developed invasive recurrence after BCS. The differences between these groups could then be used to develop a robust risk stratification tool. This tool should estimate the risk of synchronous and metachronous invasive carcinoma when DCIS is diagnosed in a biopsy. Identification of DCIS patients at low risk for developing invasive carcinoma will individualize future therapy and prevent overtreatment.

Prediction of contralateral breast cancer: external validation of risk calculators in 20 international cohorts.

BACKGROUND: Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC). METHODS: We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.8 years. Prediction performance included discrimination, quantified as a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary BC, and calibration, quantified as the expected-observed (E/O) ratio at 5 and 10 years and the calibration slope. RESULTS: The AUC at 10 years was: 0.58 (95% confidence intervals [CI] 0.57-0.59) for CBCrisk; 0.60 (95% CI 0.59-0.61) for the Manchester formula; 0.63 (95% CI 0.59-0.66) and 0.59 (95% CI 0.56-0.62) for PredictCBC-1A (for settings where BRCA1/2 mutation status is available) and PredictCBC-1B (for the general population), respectively. The E/O at 10 years: 0.82 (95% CI 0.51-1.32) for CBCrisk; 1.53 (95% CI 0.63-3.73) for the Manchester formula; 1.28 (95% CI 0.63-2.58) for PredictCBC-1A and 1.35 (95% CI 0.65-2.77) for PredictCBC-1B. The calibration slope was 1.26 (95% CI 1.01-1.50) for CBCrisk; 0.90 (95% CI 0.79-1.02) for PredictCBC-1A; 0.81 (95% CI 0.63-0.99) for PredictCBC-1B, and 0.39 (95% CI 0.34-0.43) for the Manchester formula. CONCLUSIONS: Current CBC risk prediction tools provide only moderate discrimination and the Manchester formula was poorly calibrated. Better predictors and re-calibration are needed to improve CBC prediction and to identify low- and high-CBC risk patients for clinical decision-making.

The impact of lifestyle and reproductive factors on the risk of a second new primary cancer in the contralateral breast: a systematic review and meta-analysis.

PURPOSE: The risk of being diagnosed with contralateral breast cancer (CBC) is an important health issue among breast cancer survivors. There is an increasing interest in the effect of lifestyle and reproductive factors on CBC risk, since these factors may partly be modifiable. We performed a systematic review and meta-analysis and aimed to evaluate the impact of lifestyle and reproductive factors on CBC risk in population-based breast cancer studies. METHODS: The PubMed electronic database was searched up to 2nd November 2019, for relevant publications. Of the included studies, a meta-analysis per lifestyle or reproductive factor was performed. RESULTS: Thirteen out of 784 publications were used for the meta-analysis. Body mass index (≥ 25 vs. < 25 kg/m2; RR = 1.22; 95% CI 1.01-1.47) was associated with increased CBC risk. The estimates for alcohol use (ever vs. never; RR = 1.15; 95% CI 1.02-1.31) and age at primiparity (≥ 25 vs. < 25 years; RR = 1.06; 95% CI 1.02-1.10) also showed an association with increased CBC risk. For parity (≥ 4 vs. nulliparous; RR = 0.56; 95% CI 0.42-0.76) and age at menopause (< 45 vs ≥ 45 years; RR = 0.79; 95% CI 0.67-0.93), results from two studies suggested a decreased CBC risk. We observed no association between CBC and smoking, age at menarche, oral contraceptive use, gravidity, breastfeeding, or menopausal status. Overall, the number of studies per risk factor was limited (n = 2-5). CONCLUSIONS: BMI is a modifiable risk factor for CBC. Data on the effect of other modifiable lifestyle and reproductive factors are limited. For better counseling of patients on lifestyle effects, more studies are urgently needed.