Disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and molecular subtype: prediction of axillary treatment response after neoadjuvant systemic therapy for breast cancer.

BACKGROUND: Axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT combined with pathological axillary treatment response has been proposed to guide de-escalation of axillary treatment for clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy. The aim of this study was to assess whether axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype are predictors of axillary pCR. METHODS: This study included clinically node-positive patients treated with neoadjuvant systemic therapy in the prospective Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy ('RISAS') trial (NCT02800317) with baseline [18F]fluorodeoxyglucose PET/CT imaging available. The predictive value of axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype to estimate axillary pCR was evaluated using logistic regression analysis. Discriminative ability is expressed using ORs with 95% confidence intervals. RESULTS: Overall, 185 patients were included, with an axillary pCR rate of 29.7%. The axillary pCR rate for patients with limited versus advanced baseline axillary disease according to [18F]fluorodeoxyglucose PET/CT was 31.9% versus 26.1% respectively. Axillary disease extent was not a significant predictor of axillary pCR (OR 0.75 (95% c.i. 0.38 to 1.46) (P = 0.404)). There were significant differences in axillary pCR rates between breast cancer molecular subtypes. The lowest probability (7%) was found for hormone receptor+/human epidermal growth factor receptor 2- tumours. Using this category as a reference group, significantly increased ORs of 14.82 for hormone receptor+/human epidermal growth factor receptor 2+ tumours, 40 for hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 6.91 for triple-negative tumours were found (P < 0.001). CONCLUSION: Molecular subtype is a significant predictor of axillary pCR after neoadjuvant systemic therapy, whereas axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT is not.

Quality of life of women with a screen-detected versus clinically detected breast cancer in the Netherlands: a prospective cohort study.

PURPOSE: Breast cancer (BC) screening enables early detection of BC, which may lead to improved quality of life (QoL). We aim to compare QoL between women with a screen-detected and clinically detected BC in the Netherlands. METHODS: We used data from the 'Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation' (UMBRELLA) between October 2013 and March 2022. Patients were categorized as screen-detected or clinically detected. We analysed three questionnaires, namely EORTC QLQ C-30, BR23, and HADS (Hospital Anxiety and Depression Scale) completed by BC patients shortly after diagnosis (T1) and one-year after treatment (T2). Independent t-tests were performed to compare QoL average differences between the two groups. Bonferroni-corrected p-value significance threshold of 0.00057 was used. The magnitude of differences was calculated using Cohen's d. The clinical relevance of QLQ-C30 differences was assessed based on interpretation guideline of EORTC-QLQ-C30 results. RESULTS: After applying inclusion and exclusion criteria, there were 691 women with screen-detected BC and 480 with clinically detected BC. Generally, screen-detected BC patients reported a better QoL. At T1, their average QLQ-C30 summary score was higher (86.1) than clinically detected BC patients (83.0) (p < 0.0001). Cohen's d for all items ranged between 0.00 and 0.39. A few QLQ-C30 score differences were clinically relevant, indicating better outcomes in emotional functioning, general health, constipation, and fatigue for women with screen-detected BC. CONCLUSIONS: In the Netherlands, women with screen-detected BC reported statistically significant and better QoL than women with clinically detected BC. However, clinical relevance of the differences is limited.

This study compares the quality of life (QoL) of women with breast cancer (BC) detected through screening versus through clinical detection in the Netherlands. BC screening aims to detect cancer early, potentially improving QoL. We analysed data from the UMBRELLA cohort, focusing on QoL questionnaires filled out shortly after diagnosis and one year after treatment. Results showed that women with screen-detected BC generally reported better QoL than those with clinically detected BC. For example, they had higher QLQ-C30 summary scores and several other QLQ-C30 scales and items, indicating better emotional functioning, better general health, less constipation, and less fatigue symptom. We also found that the differences in QoL are larger at one year after treatment. However, while statistically significant, the differences in QoL between the two groups were either trivial or small and may have limited clinical relevance. This study sheds light on the potential impact of mode of detection on the QoL of women with BC.

Physical Function and Physical Activity in Older Breast Cancer Survivors: 5-Year Follow-Up from the Climb Every Mountain Study.

BACKGROUND: A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline. METHODS: Patients aged ≥70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed. RESULTS: A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline -11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes. DISCUSSION: Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.

Preservation of the Pectoral Fascia in Mastectomy With Immediate Reconstruction: A Nationwide Survey.

INTRODUCTION: Pectoral fascia (PF) removal during mastectomy still seems to be the standard procedure. However, preservation of the PF might improve postoperative and cosmetic outcomes, without compromising oncological safety. Here, we report on a national survey among Dutch plastic surgeons and oncological breast surgeons to evaluate their techniques and opinions regarding the PF. MATERIALS AND METHODS: A survey based study was performed in the Netherlands, in which both plastic surgeons and oncological breast surgeons were included, each receiving a different version of the survey. The surveys were distributed to 460 and 150 e-mail addresses, respectively. RESULTS: A total of 68 responses were included from more than half of all Dutch medical centers. The results of this study indicate that circa one in five plastic surgeons and breast surgeons routinely preserve the PF during mastectomies and even more surgeons preserve the PF in specific cases. The surgical techniques and opinions regarding PF preservation widely differ between surgeons. CONCLUSIONS: Preservation of the PF does occur in a substantial part of the Dutch medical centers and techniques and opinions are contradictory. Future studies on this topic should clarify the effect of PF preservation on oncological safety, complication rates, postoperative pain, cosmetic outcomes, and patient satisfaction.

Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer.

PURPOSE: Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL). METHODS: Patients aged ≥ 70 years with stage I-III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time. RESULTS: Overall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = - 4.37; 95% CI - 7.96 to - 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = - 11.10; 95% CI - 18.80 to - 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement. CONCLUSION: A large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.

Patient-centered research: how do women tolerate nipple fluid aspiration as a potential screening tool for breast cancer?

BACKGROUND: Nipple fluid aspiration (NFA) is a technique to acquire nipple aspirate fluid (NAF), which is considered a rich source of breast-specific biomarkers. Originating directly from the mammary ducts, this liquid biopsy can offer insight into the process of carcinogenesis at its earliest stage and therefore could be of added value to the current imaging-based breast cancer screening tools. With that in mind, it is necessary to know how well NFA is tolerated. AIM: To evaluate the participants' tolerability of NFA compared to breast imaging screening methods and blood draws. MATERIALS AND METHODS: Three cohorts of women underwent NFA: healthy women (n = 190), women diagnosed with breast cancer (n = 137) and women at high risk of developing breast cancer (n = 48). A 0-10 discomfort score of NFA, mammography, breast MRI and blood draws, was filled in at the study visits, which took place once or annually. RESULTS: The median discomfort rate of NFA was 1, which was significantly lower than the median discomfort of mammography and breast MRI (5 and 3, respectively, p < 0.001), but significantly higher than median discomfort for blood draws (0, p < 0.001). The great majority of women would undergo the procedure again (98%) and recommend it to others (97%). CONCLUSION: This study shows that NFA was well tolerated by healthy women, women diagnosed with breast cancer and high-risk women. This makes NFA a feasible method to pursue as a potential future breast cancer early detection tool, based on resident biomarkers. TRIAL REGISTRATION: NL41845.041.12 , NL57343.041.16 and NL11690.041.06 in trialregister.nl.

Diagnostic Accuracy of Different Surgical Procedures for Axillary Staging After Neoadjuvant Systemic Therapy in Node-positive Breast Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to perform a systematic review and meta-analysis to assess the accuracy of different surgical axillary staging procedures compared with ALND. SUMMARY OF BACKGROUND DATA: Optimal axillary staging after neoadjuvant systemic therapy (NST) in node-positive breast cancer is an area of controversy. Several less invasive procedures, such as sentinel lymph node biopsy (SLNB), marking axillary lymph node with radioactive iodine seed (MARI), and targeted axillary dissection (a combination of SLNB and a MARI-like procedure), have been proposed to replace the conventional axillary lymph node dissection (ALND) with its concomitant morbidity. METHODS: PubMed and Embase were searched for studies comparing less invasive surgical axillary staging procedures to ALND to identify axillary burden after NST in patients with pathologically confirmed node-positive breast cancer (cN+). A meta-analysis was performed to compare identification rate (IFR), false-negative rate (FNR), and negative predictive value (NPV). RESULTS: Of 1132 records, 20 unique studies with 2217 patients were included in quantitative analysis: 17 studies on SLNB, 1 study on MARI, and 2 studies on a combination procedure. Overall axillary pathologic complete response rate was 37%. For SLNB, pooled rates of IFR and FNR were 89% and 17%. NPV ranged from 57% to 86%. For MARI, IFR was 97%, FNR 7%, and NPV 83%. For the combination procedure, IFR was 100%, FNR ranged from 2% to 4%, and NPV from 92% to 97%. CONCLUSION: Axillary staging by a combination procedure consisting of SLNB with excision of a pre-NST marked positive lymph node appears to be most accurate for axillary staging after NST. More evidence from prospective multicenter trials is needed to confirm this.

The risk of cardiovascular disease following breast cancer by Framingham risk score.

OBJECTIVES: This study evaluates the risk of cardiovascular disease (CVD) following breast cancer, accounting for baseline CVD risk. METHODS: Within the EPIC-NL (Dutch part of the European Prospective Investigation into Nutrition and Cancer) cohort, 1103 women were diagnosed with breast cancer. For every breast cancer patient, 3-4 women without breast cancer (n = 4328) were selected matched for age, year, and time since cohort enrollment. Based on CVD risk factors at cohort enrollment, 10-year risk of CVD was calculated and categorized: low (< 10%), intermediate (10-20%), high (> 20%). Cox proportional hazard models assessed the risk of CVD events (hospitalization or mortality) and CVD mortality of women with versus without breast cancer, adjusted for baseline CVD risk. RESULTS: After median follow-up of 5 and 6 years, 92 (8.3%) and 325 (7.5%) CVD events occurred in women with and without breast cancer, respectively. In the low CVD risk group, women with breast cancer had 1.44 (95% CI 1.00-2.06) times higher risk of CVD events than women without breast cancer. In the intermediate and high CVD risk categories, risk of CVD events was similar in women with and without breast cancer. Overall, women with breast cancer had 1.77 (95% CI 1.10-2.86) times higher risk of CVD mortality than women without breast cancer. CONCLUSIONS: Among women with low CVD risk, women with breast cancer have a higher risk of CVD event than women without breast cancer. Overall, women with breast cancer have a higher risk of CVD mortality than women without breast cancer.

Prognostic models in male breast cancer.

PURPOSE: Breast cancer in men is uncommon; it accounts for 1 % of all patients with primary breast cancer. Its treatment is mostly extrapolated from its female counterpart. Accurate predictions are essential for adjuvant systemic treatment decision-making and informing patients. Several predictive models are available for female breast cancer (FBC) including the Morphometric Prognostic Index (MPI), Nottingham Prognostic Index (NPI), Adjuvant! Online and Predict. The aim of this study was to examine and compare the prognostic performance of these models for male breast cancer (MBC). METHODS: The population of this study consists of 166 MBC patients. The prognostic scores of the patients are categorized by good, (moderate) and poor, defined by the test itself (MPI and NPI) or based on tertiles (Adjuvant! Online and Predict). Survival according to prognostic score was compared by Kaplan-Meier analysis and differences were tested by logRank. The prognostic performances were evaluated with C-statistics. Calibration was done with the aim to estimate to what extent the survival rates predicted by Predict were similar to the observed survival rates. RESULTS: All prediction models were capable of discriminating between good, moderate and poor survivors. P-values were highly significant. Comparison between the models using C-statistics (n = 88) showed equal performance of MPI (0.67), NPI (0.68), Adjuvant! Online (0.69) and Predict (0.69). Calibration of Predict showed overestimation for MBC patients. CONCLUSION: In conclusion, MPI, NPI, Adjuvant! and Predict prognostic models, originally developed and validated for FBC patients, also perform quite well for MBC patients.

Tablet, web-based, or paper questionnaires for measuring anxiety in patients suspected of breast cancer: patients' preferences and quality of collected data.

BACKGROUND: Electronic applications are increasingly being used in hospitals for numerous purposes. OBJECTIVE: Our aim was to assess differences in the characteristics of patients who choose paper versus electronic questionnaires and to evaluate the data quality of both approaches. METHODS: Between October 2012 and June 2013, 136 patients participated in a study on diagnosis-induced stress and anxiety. Patients were asked to fill out questionnaires at six different moments during the diagnostic phase. They were given the opportunity to fill out the questionnaires on paper or electronically (a combination of tablet and Web-based questionnaires). Demographic characteristics and completeness of returned data were compared between groups. RESULTS: Nearly two-thirds of patients (88/136, 64.7%) chose to fill out the questionnaires on paper, and just over a third (48/136, 35.3%) preferred the electronic option. Patients choosing electronic questionnaires were significantly younger (mean 47.3 years vs mean 53.5 in the paper group, P=.01) and higher educated (P=.004). There was significantly more missing information (ie, at least one question not answered) in the paper group during the diagnostic day compared to the electronic group (using a tablet) (28/88 vs 1/48, P<.001). However, in the week after the diagnostic day, missing information was significantly higher in the electronic group (Web-based questionnaires) compared to the paper group (41/48 vs 38/88, P<.001). CONCLUSIONS: Younger patients and patients with a higher level of education have a preference towards filling out questionnaires electronically. In the hospital, a tablet is an excellent medium for patients to fill out questionnaires with very little missing information. However, for filling out questionnaires at home, paper questionnaires resulted in a better response than Web-based questionnaires.

Hyperbaric Oxygen Therapy and Late Local Toxic Effects in Patients With Irradiated Breast Cancer: A Randomized Clinical Trial.

Importance: Hyperbaric oxygen therapy (HBOT) is proposed as treatment for late local toxic effects after breast irradiation. Strong evidence of effectiveness is lacking. Objective: To assess effectiveness of HBOT for late local toxic effects in women who received adjuvant radiotherapy for breast cancer. Design, Setting, and Participants: This was a hospital-based, pragmatic, 2-arm, randomized clinical trial nested within the prospective UMBRELLA cohort following the trials within cohorts design in the Netherlands. Participants included 189 women with patient-reported moderate or severe breast, chest wall, and/or shoulder pain in combination with mild, moderate, or severe edema, fibrosis, or movement restriction 12 months or longer after breast irradiation. Data analysis was performed from May to September 2023. Intervention: Receipt of 30 to 40 HBOT sessions over a period of 6 to 8 consecutive weeks. Main Outcomes and Measures: Breast, chest wall, and/or shoulder pain 6 months postrandomization measured by the European Organization for Research and Treatment of Cancer QLQ-BR23 questionnaire. Secondary end points were patient-reported fibrosis, edema, movement restriction, and overall quality of life. Data were analyzed according to intention-to-treat (ITT) and complier average causal effect (CACE) principles. Results: Between November 2019 and August 2022, 125 women (median [range] age at randomization, 56 [37-85] years) with late local toxic effects were offered to undergo HBOT (intervention arm), and 61 women (median [range] age at randomization, 60 [36-80] years) were randomized to the control arm. Of those offered HBOT, 31 (25%) accepted and completed treatment. The most common reason for not accepting HBOT was high treatment intensity. In ITT, moderate or severe pain at follow-up was reported by 58 of 115 women (50%) in the intervention arm and 32 of 52 women (62%) in the control arm (odds ratio [OR], 0.63; 95% CI, 0.32-1.23; P = .18). In CACE, the proportion of women reporting moderate or severe pain at follow-up was 32% (10 of 31) among those completing HBOT and 75% (9.7 of 12.9) among control participants expected to complete HBOT if offered (adjusted OR, 0.34; 95% CI, 0.15-0.80; P = .01). In ITT, moderate or severe fibrosis was reported by 35 of 107 (33%) in the intervention arm and 25 of 49 (51%) in the control arm (OR, 0.36; 95% CI, 0.15-0.81; P = .02). There were no significant differences in breast edema, movement restriction, and quality of life between groups in ITT and CACE. Conclusions and Relevance: In this randomized clinical trial, offering HBOT to women with late local toxic effects was not effective for reducing pain, but was effective for reducing fibrosis. In the subgroup of women who completed HBOT, a significant reduction in pain and fibrosis was observed. A smaller than anticipated proportion of women with late local toxic effects was prepared to undergo HBOT. Trial Registration: ClinicalTrials.gov Identifier: NCT04193722.

Association between endocrine therapy and cognitive decline in older women with early breast cancer: Findings from the prospective CLIMB study.

INTRODUCTION: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by the older population. Specifically, concerns have been raised regarding the detrimental effects of endocrine therapy (ET) on cognition. Therefore, we investigated cognitive functioning over time and predictors for cognitive decline in older women treated for early breast cancer. METHODS: We prospectively enrolled Dutch women aged ≥70 years with stage I-III breast cancer in the observational CLIMB study. The Mini-Mental State Examination (MMSE) was performed before ET initiation and after 9, 15 and 27 months. Longitudinal MMSE scores were analysed and stratified for ET. Linear mixed models were used to identify possible predictors of cognitive decline. RESULTS: Among the 273 participants, the mean age was 76 years (standard deviation 5), and 48% received ET. The mean baseline MMSE score was 28.2 (standard deviation 1.9). Cognition did not decline to clinically meaningful differences, irrespective of ET. MMSE scores of women with pre-treatment cognitive impairments slightly improved over time (significant interaction terms) in the entire cohort and in women receiving ET. High age, low educational level and impaired mobility were independently associated with declining MMSE scores over time, although the declines were not clinically meaningful. CONCLUSION: Cognition of older women with early breast cancer did not decline in the first two years after treatment initiation, irrespective of ET. Our findings suggest that the fear of declining cognition does not justify the de-escalation of breast cancer treatment in older women.

Mental health outcomes in older breast cancer survivors: Five-year follow-up from the CLIMB study.

BACKGROUND: There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis. METHODS: Women aged ≥70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up. RESULTS: In total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had significant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had similar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002). DISCUSSION: Depression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.

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.

Detection of breast cancer precursor lesions by autofluorescence ductoscopy.

PURPOSE: Autofluorescence is an image enhancement technique used for the detection of cancer precursor lesions in pulmonary and gastrointestinal endoscopy. This study evaluated the feasibility of addition of autofluorescence to ductoscopy for the detection of intraductal breast cancer precursor lesions. METHODS: An autofluorescence imaging system, producing real-time computed images combining fluorescence intensities, was coupled to a conventional white light ductoscopy system. Prior to surgery, ductoscopy with white light and autofluorescence was evaluated under general anaesthesia in women scheduled for therapeutic or prophylactic mastectomy. Endoscopic findings in both modes were compared, marked and correlated with histology of the surgical specimen. RESULTS: Four breast cancer patients and five high-risk women, with a median age of 47 years (range 23-62) were included. In autofluorescence mode, two intraductal lesions were seen in two breast cancer patients, which had an increase in the red-to-green fluorescence intensity compared with the surrounding tissue. One lesion had initially been missed by white light ductoscopy but was clearly visible in subsequent autofluorescence mode. One endoscopic finding was classified as suspicious by white light, but was negative in autofluorescence mode and showed normal histology. CONCLUSIONS: This study demonstrates for the first time the in vivo feasibility of autofluorescence ductoscopy to detect pathologically confirmed breast cancer precursor lesions in both breast cancer patients and high-risk women that were occult under white light.

Cytoplasmic DDX3 as prognosticator in male breast cancer.

Male breast cancer (MBC) is a rare disease. Due to its rarity, treatment is still directed by data mainly extrapolated from female breast cancer (FBC) treatment, despite the fact that it has recently become clear that MBC has its own molecular characteristics. DDX3 is a RNA helicase with tumor suppressor and oncogenic potential that was described as a prognosticator in FBC and can be targeted by small molecule inhibitors of DDX3. The aim of this study was to evaluate if DDX3 is a useful prognosticator for MBC patients. Nuclear as well as cytoplasmic DDX3 expression was studied by immunohistochemistry in a Dutch retrospective cohort of 106 MBC patients. Differences in 10-year survival by DDX3 expression were analyzed using log-rank test. The association between clinicopathologic variables, DDX3 expression, and survival was tested in uni- and multivariate Cox-regression analysis. High cytoplasmic DDX3 was associated with high androgen receptor (AR) expression while low nuclear DDX3 was associated with negative lymph node status. Nuclear and cytoplasmic DDX3 were not associated with each other. In a univariate analysis, high cytoplasmic DDX3 (p = 0.045) was significantly associated with better 10-year overall survival. In multivariate analyses, cytoplasmic DDX3 had independent prognostic value (p = 0.017). In conclusion, cytoplasmic DDX3 expression seems to be a useful prognosticator in MBC, as high cytoplasmic DDX3 indicated better 10-year survival.

Compression Vest Treatment for Symptomatic Breast Edema in Women Treated for Breast Cancer: A Pilot Study.

Background: Lymphedema of the breast/chest wall after breast cancer treatment is often associated with pain and reduced quality of life. We conducted a pilot study to evaluate whether the use of a compression vest reduced symptoms of breast/chest wall edema in breast cancer patients. Methods and Results: This single-center study included patients (n = 25) with symptomatic breast/chest wall edema with a pain score of ≥3 on the Numerical Rating Scales (range 1-10). The patients were instructed to wear a compression vest (Lymphatrex, Class II) for 6 months. Wilcoxon signed-rank tests were used to compare differences in patient-reported pain intensity/severity. Analyses included all patients with available data. In total, 17 (68%) continued to wear their vests for 6 months, whereas the other 8 withdrew prematurely. At baseline, median pain severity (4.9, interquartile range [IQR] 3.6-6.0) and pain interference (4.3, IQR 2.1-5.9) scores were significantly higher compared with pain scores after wearing the compression vest for 6 months (1.8 IQR 1.0-4.8 and 1.4 IQR 0.9-4.4, resp.). Patient-reported breast/chest wall swelling decreased from 92% (n = 22) at baseline to 71% (n = 12) at 6 months. The prevalence of moderate/severe patient-reported breast/chest wall pain declined from 63% (n = 15) at baseline to 18% (n = 3) at 6 months. Physical, emotional, and social functioning improved over time and was comparable to scores of the Dutch reference population. Conclusion: The results of this pilot study suggest that a compression vest could be an acceptable and effective treatment option for patients with painful breast/chest wall edema. In compliant patients, swelling and pain was significantly reduced.

Impact on Quality of Documentation and Workload of the Introduction of a National Information Standard for Tumor Board Reporting.

PURPOSE: Tumor boards, clinical practice guidelines, and cancer registries are intertwined cancer care quality instruments. Standardized structured reporting has been proposed as a solution to improve clinical documentation, while facilitating data reuse for secondary purposes. This study describes the implementation and evaluation of a national standard for tumor board reporting for breast cancer on the basis of the clinical practice guideline and the potential for reusing clinical data for the Netherlands Cancer Registry (NCR). METHODS: Previously, a national information standard for breast cancer was derived from the corresponding Dutch clinical practice guideline. Using data items from the information standard, we developed three different tumor board forms: preoperative, postoperative, and postneoadjuvant-postoperative. The forms were implemented in Amphia Hospital's electronic health record. Quality of clinical documentation and workload before and after implementation were compared. RESULTS: Both draft and final tumor board reports were collected from 27 and 31 patients in baseline and effect measurements, respectively. Completeness of final reports increased from 39.5% to 45.4% (P = .04). The workload for tumor board preparation and discussion did not change significantly. Standardized tumor board reports included 50% (61/122) of the data items carried in the NCR. An automated process was developed to upload information captured in tumor board reports to the NCR database. CONCLUSION: This study shows implementation of a national standard for tumor board reports improves quality of clinical documentation, without increasing clinical workload. Simultaneously, our work enables data reuse for secondary purposes like cancer registration.

Prognostic factors in 77 curative chest wall resections for isolated breast cancer recurrence.

BACKGROUND: Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent. METHODS: BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed. RESULTS: Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (P = .02 and .004, respectively), (2) chemotherapy for recurrence (P = .05 and .05, respectively), and (3) resection specimen smaller than 150 cm2 (P = .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses. CONCLUSIONS: CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of >or= 10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients.

Breast Edema Following Breast-Conserving Surgery and Radiotherapy: Patient-Reported Prevalence, Determinants, and Effect on Health-Related Quality of Life.

BACKGROUND: The association between lymphedema of the arm and impaired health-related QoL (HR-QoL) has led to changes in clinical practice. However, data on lymphedema of the breast (ie, breast edema) are lacking. We prospectively evaluated patient-reported prevalence and determinants of breast edema and its effect on patient-reported HR-QoL and breast pain. METHODS: We prospectively included 836 patients undergoing breast-conserving surgery followed by radiotherapy between October 2013 and October 2016 (UMBRELLA cohort). Patient-reported breast edema, HR-QoL, and breast pain were assessed by means of European Organisation for Research and Treatment of Cancer-C30/BR23 before starting radiotherapy and at 3, 6, 12, and 18 months thereafter. We assessed which patient, tumor, and treatment characteristics were associated with breast edema. With mixed-effects models, we assessed the impact of breast edema on patient-reported HR-QoL domains and breast pain over time, adjusting for confounders. RESULTS: Within a median follow-up of 28 months (interquartile range [IQR] = 15), 207 (24.8%) patients reported breast edema at some point in time. Prevalence of breast edema was highest at 6 months (12.4%, 95% confidence interval [CI] = 10.0 to 14.7). Larger tumor size, oncoplastic surgery, axillary lymph node dissection, locoregional radiotherapy, radiotherapy boost on the tumor bed, and adjuvant chemotherapy were associated with breast edema. Breast edema was independently associated with more breast pain and with poorer QoL, physical functioning, and body image. CONCLUSIONS: Breast edema occurs frequently within the first year after breast-conserving surgery and radiotherapy and is independently associated with impaired HR-QoL and more breast pain. This information is important for use in clinical practice and should be discussed with patients during shared decision making.