Seizing the moment: The time for harnessing electronic patient-reported outcome measures for enhanced and sustainable metastatic breast cancer care is now.

The sustainability of healthcare systems is under pressure. Unlike care for many other chronic diseases, cancer care has yet to empower patients in effectively self-managing both the medical and emotional consequences of their condition, including adapting to changes in lifestyle and work, which is essential to achieve optimal health and recovery. Although proposed as a potential solution for sustainable healthcare and support for optimal health and recovery already decades ago, practical implementation of digital care lags behind. We believe electronic patient reported outcome measures (ePROMs) could play an important role in creating sustainable healthcare, both to guide complex treatment pathways and to empower survivors to self-manage consequences of diagnosis and treatment. That is, ePROMs can be used for screening and monitoring of symptoms, but also for treatment decision-making and to facilitate communication about quality of life. We therefore see opportunities for improvements in quality of care, quality of life, and survival of cancer patients, as well as research opportunities, as ePROMs collection can lead to better understanding of care needs. The '10 Actions for Change report' of the Advanced Breast Cancer Global Alliance stresses a critical need for improvement of care for metastatic breast cancer (MBC) patients. We therefore in this paper focus on MBC care and research.

Health-related quality of life (HRQoL) after different axillary treatments in women with breast cancer: a 1-year longitudinal cohort study.

PURPOSE: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. METHODS: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. RESULTS: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p < 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p < 0.05). CONCLUSION: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.

International development of a patient-centered core outcome set for assessing health-related quality of life in metastatic breast cancer patients.

PURPOSE: For patients living with metastatic breast cancer (MBC), achieving best possible health-related quality of life, along with maximizing survival, is vital. Yet, we have no systemic way to determine if we achieve these goals. A Core Outcome Set (COS) that allows standardized measurement of outcomes important to patients, but also promotes discussing these outcomes during clinical encounters, is long overdue. METHODS: An international expert group (EG) of patient advocates, researchers, medical specialists, nurse specialists, and pharmaceutical industry representatives (n = 17) reviewed a list of relevant outcomes retrieved from the literature. A broader group (n = 141: patients/patient advocates (n = 45), health care professionals/researchers (n = 64), pharmaceutical industry representatives (n = 28), and health authority representatives (n = 4)) participated in a modified Delphi procedure, scoring the relevance of outcomes in two survey rounds. The EG finalized the COS in a consensus meeting. RESULTS: The final MBC COS includes 101 variables about: (1) health-related quality of life (HRQoL, n = 26) and adverse events (n = 24); (2) baseline patient characteristics (n = 9); and (3) clinical variables (n = 42). Many outcome that cover aspects of HRQoL relevant to MBC patients are included, e.g. daily functioning (including ability to work), psychosocial/emotional functioning, sexual functioning, and relationship with the medical team. CONCLUSION: The COS developed in this study contains important administrative data, clinical records, and clinician-reported measures that captures the impact of cancer. The COS is important for standardization of clinical research and implementation in daily practice and has received accreditation by the International Consortium for Health Outcomes Measurement (ICHOM).

Predictors of delayed breast reconstruction in the Netherlands: a 5-year follow-up study in stage I-III breast cancer patients.

PURPOSE: Delayed breast reconstruction (DBR) is a valid option for postmastectomy breast cancer patients who have a desire for breast reconstruction but are not considered suitable for immediate breast reconstruction (IBR). The objective of this study was to investigate the clinical practice and predictors of the use of DBR in the Netherlands. METHODS: Stage I-III breast cancer patients diagnosed from January to March 2012 and treated with mastectomy were selected from the Netherlands Cancer Registry. Routinely collected patient, tumor, treatment and hospital characteristics were complemented with data about DBR up to 2018. Multivariable logistic regression analyses were performed to identify factors independently associated with postmastectomy DBR. Factors associated with time to DBR were identified through Cox regression analyses. RESULTS: Of all patients who underwent mastectomy (n = 1,415), 10.2% underwent DBR. DBR patients more often received autologous reconstruction compared to IBR patients (37.5% vs 6.2%, p < 0.001). Age below 50 years (age < 35 OR 15.55, age 35-49 OR 4.18) and neoadjuvant and adjuvant chemotherapy (OR 2.59 and OR 2.83, respectively) were significantly associated with DBR. Mean time to DBR was 2.4 years [range 1-6 years]. Time to DBR was significantly associated with age < 35 years (HR 2.22), and a high hospital volume (HR 1.87). DISCUSSION: The use of DBR after mastectomy could not be fully explained by age below 50 years, chemotherapy, and hospital volume. Treatment with radiotherapy and adjuvant chemotherapy increased time to DBR. More information about patient preferences is needed to understand the use and timing of reconstruction.

De-escalation of axillary surgery in breast cancer patients treated in the neoadjuvant setting: a Dutch population-based study.

PURPOSE: An overall trend is observed towards de-escalation of axillary surgery in patients with breast cancer. The objective of this study was to evaluate this trend in patients treated with neoadjuvant systemic therapy (NST). METHODS: Patients with cT1-4N0-3 breast cancer treated with NST (2006-2016) were selected from the Netherlands Cancer Registry. Patients were classified by clinical node status (cN) and type of axillary surgery. Uni- and multivariable logistic regression analyses were performed to determine the clinicopathological factors associated with performing ALND in cN+ patients. RESULTS: A total of 12,461 patients treated with NST were identified [5830 cN0 patients (46.8%), 6631 cN+ patients (53.2%)]. In cN0 patients, an overall increase in sentinel lymph node biopsy (SLNB) only (not followed by ALND) was seen from 11% in 2006 to 94% in 2016 (p < 0.001). SLNB performed post-NST increased from 33 to 62% (p < 0.001). In cN+ patients, an overall decrease in ALND was seen from 99% in 2006 to 53% in 2016 (p < 0.001). Age (OR 1.01, CI 1.00-1.02), year of diagnosis (OR 0.47, CI 0.44-0.50), HER2-positive disease (OR 0.62, CI 0.52-0.75), clinical tumor stage (T2 vs. T1 OR 1.32, CI 1.06-1.65, T3 vs. T1 OR 2.04, CI 1.58-2.63, T4 vs. T1 OR 6.37, CI 4.26-9.50), and clinical nodal stage (N3 vs. N1 OR 1.65, CI 1.28-2.12) were correlated with performing ALND in cN+ patients. CONCLUSIONS: ALND decreased substantially over the past decade in patients treated with NST. Assessment of long-term prognosis of patients in whom ALND is omitted after NST is urgently needed.

Patient-Reported Outcome Measures may optimize shared decision-making for cancer risk management in BRCA mutation carriers.

PURPOSE: The aim of this study was to compare patient-reported outcomes (PROs) of BRCA1/2 mutation carriers, either after bilateral prophylactic mastectomy (BPM) or during breast surveillance, to improve shared decision-making in their cancer risk management. METHODS: Unaffected BRCA1/2 mutation carriers at least one year after BPM followed by immediate breast reconstruction (BPM-IBR) or one year under surveillance were eligible. After informed consent, the Hospital Anxiety and Depression Scale (HADS) and BREAST-Q were administered and compared between the different strategies. PROs were also compared to available normative data. RESULTS: Ninety-six participants were analyzed in this study and showed significant differences between strategies in age, age at genetic testing, and time since BPM or starting breast surveillance. All HADS scores were below 8 suggesting no signs of anxiety or depression in both groups. Higher mean 'Q-physical well-being' scores were reported by the surveillance group (81.78 [CI 76.99-86.57]) than the BPM group (76.96 [CI 73.16 - 80.75]; p = 0.011). Overall, for both questionnaires better scores were seen when compared to age-matched normative data. CONCLUSIONS: No signs of anxiety or depression were seen in the surveillance or BPM-IBR group. Slightly better mean BREAST-Q scores were seen for the surveillance group in comparison to BPM-IBR, except for 'Q-psychological well-being'. The difference in 'Q-physical well-being' was significantly worse for BPM-IBR. Approaches to obtain longitudinal PROs and reference values should be explored in the future, which could add value to shared decision-making in regards to breast cancer risk management in this specific patient population.

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists.

INTRODUCTION: Various options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists. MATERIALS AND METHODS: A survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST. RESULTS: A total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND. CONCLUSION: Current axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.

Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer.

BACKGROUND: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. METHODS: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. RESULTS: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). CONCLUSION: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease.

ANTECEDENTES: En el cáncer de mama con ganglios positivos clínicamente tras el tratamiento neoadyuvante sistémico, se ha propuesto la utilización de iodo radioactivo (Marking Axilla with Radioactive Iodine, MARI) y de la biopsia de ganglio linfático centinela para la estadificación axilar. En este estudio se evaluó la tasa de identificación y detección de enfermedad residual cuando se combinó la exéresis de los ganglios linfáticos marcados antes del tratamiento (marked lymph nodes, MLN) junto con los ganglios centinela (sentinel lymph nodes, SLN). MÉTODOS: Se realizó un análisis retrospectivo multicéntrico de pacientes con cáncer de mama con ganglios positivos clínicamente que se sometieron a tratamiento neoadyuvante sistémico y en las que se combinaron ambas técnicas (con o sin disección axilar). Se calcularon las tasas de identificación y detección de enfermedad residual axilar para MLN y SLN por separado y en conjunto. RESULTADOS: En 138/139 pacientes se identificaron ≥ 1 MLN y/o SLN combinando ambas técnicas (tasa de identificación del 99,3%). La tasa de identificación fue de 92,8% para MLN y del 87,8% para SLN. Combinando ambas técnicas se detectó enfermedad axilar residual en 88/139 (63,3%) pacientes. Se detectó enfermedad residual en 20/88 (22,7%) pacientes utilizando únicamente MLN, en 10/88 (11,4%) pacientes utilizando únicamente SLN y en 58/88 (65,9%) combinando ambas técnicas. CONCLUSIÓN: La exéresis conjunta de los ganglios marcados con iodo radioactivo antes del tratamiento neoadyuvante sistémico y de los ganglios centinela después del tratamiento en pacientes con cN+ logró una tasa de identificación más alta y una mejor detección de la enfermedad axilar residual.

Implementation of Value Based Breast Cancer Care.

PURPOSE: Adding value of care to patients is crucial for all stakeholders. The use of both provider and patient reported outcome data was implemented in a single academic breast cancer center. We describe the development of the outcomes set, data integration within electronical health records (EHR) and clinical use. METHODS: An Integrated Practice Unit (IPU) was constructed providing the full care cycle for breast cancer patients. Provider reported outcomes and patient reported outcomes (PROs) were defined, reflecting the entire cycle of care and long-term sustainability of quality of life. Multidisciplinary provider and patient perspectives were obtained via focus groups and surveys. Patient pathways were redesigned in order to identify suitable opportunities for data collection during the entire care cycle. RESULTS: A Standard Set for Breast Cancer Outcomes together with case-mix variables and timelines was agreed upon within the IPU. A secure electronic platform, directly linked to the EHR, was designed to measure PROs during the outpatient phase. First year evaluation showed a decrease of response rates over time, from 83.3% at baseline to 45.2% at 12 months after surgery. Patients reacted positively to the use of PROMs in daily clinical cancer care. CONCLUSION: Assessment of patient reported as well as provider reported outcomes was implemented within our standard of breast cancer care. For this, dedicated resources, change of culture and practice, and improved knowledge and awareness about Value-based healthcare (VBHC) were essential. Our proposed framework aims to serve as a blueprint for implementation of VBHC in daily care.

Patient-Reported Outcome Measures May Add Value in Breast Cancer Surgery.

PURPOSE: Considering the comparable prognosis in early-stage breast cancer after breast-conserving therapy (BCT) and mastectomy, quality of life should be a focus in treatment decision(s). We retrospectively collected PROs and analyzed differences per type of surgery delivered. We aimed to obtain reference values helpful in shared decision-making. PATIENTS AND METHODS: pTis-T3N0-3M0 patients operated between January 2005 and September 2016 were eligible if: (1) no chemotherapy was administered < 6 months prior to enrolment, and (2) identical surgeries were performed in case of bilateral surgery. After consent, EQ-5D-5L, EORTC-QLQ-C30/BR23, and BREAST-Q were administered. PROs were evaluated per baseline characteristics using multivariable linear regression models. Outcomes were compared for different surgeries as well as for primary (PBC) and second primary or recurrent (SBC) breast cancer patients using analyses of variance (ANOVAs). RESULTS: The response rate was 68%. PROs in 612 PBC patients were comparable to those in 152 SBC patients. Multivariable analyses showed increasing age to be associated with lower "physical functioning" [ß - 0.259, p < 0.001] and "sexual functioning" [ß - 0.427, p < 0.001], and increasing time since surgery with less "fatigue" [ß - 1.083, p < 0.001]. Mastectomy [ß - 13.596, p = 0.003] and implant reconstruction [ß - 13.040, p = 0.007] were associated with lower "satisfaction with breast" scores than BCT. Radiation therapy was associated with lower satisfaction scores than absence of radiotherapy. DISCUSSION: PRO scores were associated with age, time since surgery, type of surgery, and radiation therapy in breast cancer patients. The scores serve as a reference value for different types of surgery in the study population and enable prospective use of PROs in shared decision-making.

Nationwide population-based study of trends and regional variation in breast-conserving treatment for breast cancer.

BACKGROUND: Landmark trials have shown breast-conserving surgery (BCS) combined with radiotherapy to be as safe as mastectomy in breast cancer treatment. This population-based study aimed to evaluate trends in BCS from 1989 to 2015 in nine geographical regions in the Netherlands. METHODS: All women diagnosed between 1989 and 2015 with primary T1-2 N0-1 breast cancer, treated with BCS or mastectomy, were identified from the Netherlands Cancer Registry. Crude and case mix-adjusted rates of BCS were evaluated and compared between nine Dutch regions for two time intervals: 1989-2002 and 2003-2015. The annual percentage change in BCS per region over time was assessed by means of Joinpoint regression analyses. Explanatory variables associated with the choice of initial surgery were evaluated using multivariable logistic regression. RESULTS: A total of 202 934 patients were included, 82 200 treated in 1989-2002 and 120 734 in 2003-2015. During 1989-2002, the mean rate of BCS was 50·6 per cent, varying significantly from 39·0 to 71·7 per cent between the nine regions. For most regions, a marked rise in BCS was observed between 2002 and 2003. During 2003-2015, the mean rate of BCS increased to 67·4 per cent, but still varied significantly between regions from 58·5 to 75·5 per cent. A significant variation remained after case-mix correction. CONCLUSION: This large nationwide study showed that the use of BCS increased from 1989 to 2015 in the Netherlands. After adjustment for explanatory variables, a large variation still existed between the nine regions. This regional variation underlines the need for implementation of a uniform treatment and decision-making strategy.

Breast cancer-related deaths according to grade in ductal carcinoma in situ: A Dutch population-based study on patients diagnosed between 1999 and 2012.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has drastically increased over the past decades. Because DCIS is resected after diagnosis similar to invasive breast cancer, the natural cause and behaviour of DCIS is not well known. We aimed to determine breast cancer-specific survival (BCSS) and overall survival (OS) according to grade in DCIS patients after surgical treatment in the Netherlands. PATIENTS AND METHODS: All DCIS patients diagnosed between 1999 and 2012 were selected from the Netherlands Cancer Registry. The cause of death was obtained from 'Statistics Netherlands'. BCSS and OS were estimated using multivariable Cox regression in the entire cohort and stratified for grades. RESULTS: In total, 12,256 patients were included, of whom 1509 (12.3%) presented with grade I, 3675 (30.0%) with grade II, 6064 (49.5%) with grade III and 1008 (8.2%) with an unknown grade. During a median follow-up of 7.8 years, 1138 (9.3%) deaths were observed, and 179 (1.5%) were breast cancer-related. Of these, 10 patients had grade I; 46 grade II; 95 grade III and 28 an unknown grade. After adjustment for confounding, grade II and III were related to worse BCSS than grade I with hazard ratios of 1.92 (95% confidence interval [CI]: 0.97-3.81) and 2.14 (95% CI: 1.11-4.12), respectively. No association between grades and OS was observed. CONCLUSION: BCSS and OS in DCIS patients were excellent. Because superior rates were observed for low-grade DCIS, it seems justified to investigate whether active surveillance may be a balanced alternative for conventional surgical treatment.

Three-dimensional ultrasonography of the breast; An adequate replacement for MRI in neoadjuvant chemotherapy tumour response evaluation? - RESPONDER trial.

BACKGROUND: Accurate measurement of tumour response during and after neoadjuvant chemotherapy (NAC) is important and may influence treatment decisions in invasive breast cancer patients. Breast MRI forms the gold standard but is more burdensome, time consuming and costly. In this study response measurement was done with 3-D ultrasound by Automated Breast Volume Scanner (ABVS) and compared to breast MRI. Moreover, patient satisfaction with both techniques was compared. METHODS AND MATERIALS: A single-institution, prospective observational pilot study evaluating tumour response by ABVS in addition to breast MRI (standard care) was performed in 25 invasive breast cancer patients receiving NAC. Tumour response was evaluated comparing longest tumour diameters as well as tumour volumes at predefined time points using Bland-Altman analysis. Volume measurements for breast MRI were obtained using a fully immersive virtual reality system (a Barco I-Space) and V-Scope software. Same software was used to obtain ABVS volume measurements using an in-house developed desktop VR system. Inter- and intra-observer agreement was evaluated by Intraclass Correlation Coefficient (ICC). RESULTS: Twenty-five patients were eligible for baseline measurement, 20 for a mid-NAC response evaluation, and five for a post-NAC response evaluation. MRI and ABVS showed absolute concordance in 73% of patients for the mid-NAC evaluation, with a 'good' correlation for the difference in longest diameter measurement (ICC 0.73, p < 0.01) as compared to baseline assessment. Concerning difference in volume measurement in the mid-NAC response evaluation showed a 'fair' correlation (ICC 0.52, p < 0.01) and in the post-NAC response evaluation an 'excellent' correlation (ICC 0.98, p < 0.01). 'Excellent' inter- and intra-observer agreement was found (ICC 0.88, p < 0.01) with comparable limits of agreement (LOA) for observer 1 and 2 in both diameter and volume measurement. Patient satisfaction was higher for ABVS compared to breast MRI, 93% versus 12% respectively. CONCLUSION: ABVS showed 'good' correlation with MRI tumour response evaluation in breast cancer patients during NAC with 'excellent' inter- and intra-observer agreement. ABVS has patients' preference over breast MRI and could be considered as alternative to breast MRI, in case results on an on-going prospective trial confirm these results (NTR6799).

Patient reported outcome measures in breast cancer patients.

INTRODUCTION: In the International Consortium for Health Outcome Measures (ICHOM) breast cancer outcome set Patient Reported Outcome Measurements (PROMs) form an important but rather innovative part. Few data exist on scores per type of breast surgery and how to use scores in surgical practice. We evaluated PROM scores as well as satisfaction with and expectations of the use of PROMs in breast cancer patients using the national and local patient advocate society. METHODS: Through an online survey patients were asked to report age, type of breast cancer surgery (whether Breast Conserving Therapy (BCT), mastectomy, autologous or implant breast reconstruction) and time since surgery. PROMs (EORTC-QLQ-C30/BR23 and BREAST-Q postoperative modules) were compared for the different surgeries. Additional comparison was made with literature normative and reference scores. Three questions evaluated satisfaction with PROMs and expectations. RESULTS: 496 patients completed all PROMs and 487 the satisfaction/expectation-questions. Significantly reduced physical functioning was reported following BCT as compared to other surgeries and literature reference values. Satisfaction scores were higher following autologous reconstruction and lower following implant reconstruction as compared to BCT. PRO scores were comparable to normative and references scores except for the 'physical functioning' (BREAST-Q) scores that reported lower in the present study. Ninety-four percent of the participants was (highly) satisfied with future PROM use. CONCLUSIONS: Statistical significant differences were found for PROMs following different types of breast surgery. The significance of these results should become clearer trough collection of future data. The great majority of participants considered PROMs as (highly) acceptable and reacted positively on their proposed future use.

Breast and Tumour Volume Measurements in Breast Cancer Patients Using 3-D Automated Breast Volume Scanner Images.

BACKGROUND: The resection volume in relation to the breast volume is known to influence cosmetic outcome following breast-conserving therapy. It was hypothesised that three-dimensional ultrasonography (3-D US) could be used to preoperatively assess breast and tumour volume and show high association with histopathological measurements. METHODS: Breast volume by the 3D-US was compared to the water displacement method (WDM), mastectomy specimen weight, 3-D MRI and three different calculations for breast volume on mammography. Tumour volume by the 3-D US was compared to the histopathological tumour volume and 3-D MRI. Relatedness was based on the intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (95% CI). Bland-Altman plots were used to graphically display the agreement for the different assessment techniques. All measurements were performed by one observer. RESULTS: A total of 36 patients were included, 20 and 23 for the evaluation of breast and tumour volume (ductal invasive carcinomas), respectively. 3-D US breast volume showed 'excellent' association with WDM, ICC 0.92 [95% CI (0.80-0.97)]. 3-D US tumour volume showed a 'excellent' association with histopathological tumour volume, ICC 0.78 [95% CI (0.55-0.91)]. Bland-Altman plots showed an increased overestimation in lager tumour volumes measured by 3-D MRI compared to histopathological volume. CONCLUSIONS: 3-D US showed a high association with gold standard WDM for the preoperative assessment of breast volume and the histopathological measurement of tumour volume. 3-D US is an patient-friendly preoperative available technique to calculate both breast volume and tumour volume. Volume measurements are promising in outcome prediction of intended breast-conserving treatment.

Focally positive margins in breast conserving surgery: Predictors, residual disease, and local recurrence.

BACKGROUND: Re-excision after breast conserving surgery (BCS) for invasive breast cancer (IBC) can be omitted for focally positive margins in the Netherlands, but this guideline is not routinely followed. Focally positive and extensively positive margins have rarely been studied separately and compared to negative margins regarding clinicopathological predictors, residual disease incidence, and local recurrence. METHODS: All females with BCS for Tis-T3, without neo-adjuvant chemotherapy between 2005 and 2014 at one university hospital were included. Clinicopathological and follow-up information was collected from electronic patient records. Index tumor samples from all patients with re-excision were reviewed by one pathologist. Margins were classified as negative (≥2 mm width), close (<2 mm width), focally positive (≤4 mm length of tumor touching inked margin), or extensively positive (>4 mm length). RESULTS: From 499 patients included, 212 (43%) had negative, 161 (32%) had close, 59 (12%) had focally positive, and 67 (13%) had extensively positive margins. Increasingly involved margins were associated with lobular type, tumor size, and adjacent DCIS in IBC patients and lesion size in purely DCIS patients. In IBC patients, 17%, 49%, and 77% had re-excision after close, focally positive, and extensively positive margins and residual disease incidence was 55%, 50%, and 70% respectively. In purely DCIS patients, 26 (65%), 13 (87%), and 16 (94%) had re-excision after close, focally positive, and extensively positive margins and residual disease incidence was 39%, 46%, and 90% respectively. CONCLUSION: Incidence of residual disease after focally positive margins was not different from close margins, but was significantly higher after extensively positive margins. We recommend quantifying extent of margin involvement in all pathology reports.

TUmor-volume to breast-volume RAtio for improving COSmetic results in breast cancer patients (TURACOS); a randomized controlled trial.

BACKGROUND: Cosmetic result following breast conserving surgery (BCS) for cancer influences quality of life and psychosocial functioning in breast cancer patients. A preoperative prediction of expected cosmetic result following BCS is not (yet) standard clinical practice and therefore the choice for either mastectomy or BCS is still subjective. Recently, we showed that tumour volume to breast volume ratio as well as tumour location in the breast are independent predictors of superior cosmetic result following BCS. Implementation of a prediction model including both factors, has not been studied in a prospective manner. This study aims to improve cosmetic outcome by implementation of a prediction model in the treatment decision making for breast cancer patients opting for BCS. METHODS/DESIGN: Multicentre, single-blinded, randomized controlled trial comparing standard preoperative work-up to a preoperative work-up with addition of the prediction model. Tumour volume to breast volume ratio and tumour location in the breast will be used to predict cosmetic outcome in invasive breast cancer patients opting for BCS. Three dimensional (3D)-ultrasonography will be used to measure the tumour volume to breast volume ratio needed for the prediction model. Sample size was estimated based on a 14% improvement in incidence of superior cosmetic result one year after BCS (71% in the control group versus 85% in the intervention group). Primarily cosmetic outcome will be evaluated by a 6-member independent panel. Secondary endpoints include; (1) patient reported outcome measured by BREAST-Q, EORTC-QLQ-C30/BR23 and EQ-5D-5 L (2) cosmetic outcome as assessed through the BCCT.core software, (3) radiation-induced reaction (4) surgical treatment performed, (5) pathological result and (6) cost-effectiveness. Follow-up data will be collected for 3 years after surgery or finishing radiotherapy. DISCUSSION: This randomized controlled trial examines the value of a preoperative prediction model for the treatment-decision making. It aims for a superior cosmetic result in breast cancer patients opting for BCS. We expect improvement of patients' quality of life and psychosocial functioning in a cost-effective way. TRIAL REGISTRATION: Prospectively registered, February 17th 2015, at 'Nederlands Trialregister - NTR4997 '.

[Preventive contralateral mastectomy despite absence of gene mutation; management and treatment of women with no medical indication]. / Geen aangetoonde genmutatie, maar toch preventieve contralaterale mastectomie.

Recently, there has been an increase in the rate of contralateral prophylactic mastectomies (CPM) as a therapy for breast cancer. The CPM is performed to achieve a reduction in the risk of developing asecond breast cancer. However, evidence is lacking for beneficial survival outcomes after a CPM in patients without a gene mutation, and complications of surgery are inevitable. Currently there are no evidence-based clinical practice guidelines available for clinicians to decide upon the right treatment for patients without a gene mutation. Our hospitals have therefore implemented their own clinical pathway to achieve a comprehensive treatment for this group of patients. In this article we will provide an overview of the existing literature and illustrate our clinical pathway by presenting three patients treated in our hospitals in the last two years.