Impact of the 2008 economic crisis on the burden of hepatitis B and C diseases in Southern European countries.

BACKGROUND: The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease. METHODS: Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019. RESULTS: Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV. CONCLUSIONS: Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries.

Respiratory complex I regulates dendritic cell maturation in explant model of human tumor immune microenvironment.

BACKGROUND: Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level. METHODS: Here we establish a patient-derived explant culture (PDEC) model of breast cancer, which retains the immune contexture of the primary tumor, recapitulating cytokine profiles and CD8+T cell cytotoxic activity. RESULTS: We explored the immunomodulatory action of a synthetic lethal BCL2 inhibitor venetoclax+metformin drug combination ex vivo, discovering metformin cannot overcome the lymphocyte-depleting action of venetoclax. Instead, metformin promotes dendritic cell maturation through inhibition of mitochondrial complex I, increasing their capacity to co-stimulate CD4+T cells and thus facilitating antitumor immunity. CONCLUSIONS: Our results establish PDECs as a feasible model to identify immunomodulatory functions of anticancer drugs in the context of patient-specific TIME.

Vacuum-assisted excision of small breast cancers under ultrasound guidance.

PURPOSE: The purpose of this study was to evaluate if it is possible to completely remove small breast cancer tumours with vacuum-assisted excision (VAE) under ultrasound guidance. METHODS: Women ≥ 50 years old with a biopsy proven invasive cancer ≤ 10 mm were selected between October 2021 and November 2021 based on referrals and enrolled in this prospective study. The patients underwent VAE within six weeks following biopsy to remove the tumour. After the tumour was excised and the biopsy cavities margins were shaved, a radioactive seed was inserted into the biopsy cavity. The VAE excision cavity and surrounding tissue were surgically excised. Preliminary VAE results were evaluated after ten patients. For the study to proceed at least 80 % of the breast cancer tumours had to be completely removed by VAE. RESULTS: The tumours median size in mammography was 8.5 mm (6-9 mm) and in ultrasound 6.5 mm (4-9 mm). The shape of the lesion was round in three (30 %), oval in two (20 %) and irregular in five (50 %) patients. None of the tumours were completely removed in the first VAE specimen, meaning that there was invasive cancer or ductal carcinoma in situ (DCIS) in the "shaved margins" and/or the surgical specimen. In five (50 %) cases, the surgical specimen was free of invasive cancer and DCIS. CONCLUSIONS: None of the small invasive breast cancers were completely excised with VAE under ultrasound guidance, therefore it is not a reliable method to remove small breast cancers.

Reoperation rate of ductal carcinoma in situ: impact of tomosynthesis (3D) and spot magnification.

BACKGROUND: Surgical planning depends on precise preoperative assessment of the radiological extent of ductal carcinoma in situ (DCIS). Despite different modalities used, reoperation rates for DCIS due to involved margins are high. PURPOSE: To evaluate the impact of additional imaging views (spot magnification, tomosynthesis) on surgical reoperation rate of DCIS. MATERIAL AND METHODS: The retrospective single institute study includes 157 patients with biopsy-proven pure DCIS seen on mammogram as microcalcifications and treated with breast-conserving surgery. Patients have been divided into three groups according to additional imaging performed: spot magnification, tomosynthesis, and none. All breast images (mammograms, spot magnification, tomosynthesis) were reviewed and the maximum extent of pathological microcalcifications was recorded. Radiological size was compared to final histopathological size. Reoperation rate due to inadequate margins was recorded. RESULTS: Reoperation rates (25%) due to inadequate margins were as follows: spot (18%), tomosynthesis (27%), none (31%); P = 0.488. Spot magnification, tomosynthesis, and digital zoom of full-field digital mammography predicted similarly the final histopathological size. Reoperation group had a significantly greater preoperative radiological median size (26 mm vs. 20 mm; P = 0.014) as well as median size of disease on final histopathological report (29 mm vs. 14 mm; P < 0.001). Discrepancy between radiological and final histopathological size became greater with increasing DCIS extent. CONCLUSION: The main factors for reoperations are DCIS size and discordance between radiological and histopathological sizes. The use of additional imaging views (spot magnification, tomosynthesis) did not reduce reoperation rate.

Long-Term Survival Outcomes of Patients with Small (≤1 cm) Node-Negative HER2-Positive Breast Cancer Not Treated with Adjuvant Anti-HER2-Targeted Therapy: A 10-Year Follow-Up Study.

Introduction: Human epidermal growth factor receptor 2 (HER2) expression is considered an unfavourable prognostic factor in early breast cancer when the patients are not treated with HER2-targeted therapy. However, the long-term prognostic importance of HER2 expression in small (≤1 cm, stage pT1a-b), node-negative HER2* breast cancer is still incompletely known. Methods: A retrospective analysis was performed based on a prospectively collected database including patients with pT1 breast cancer operated at the Helsinki University Hospital, Finland, between March 2000 and April 2006. In this database, 44 patients with pT1a-bN0M0, HER2* cancer, not treated with adjuvant anti-HER2-targeted therapy (the HER2* group) and 291 pT1a-bN0M0, hormone receptor-positive, HER2-negative cancers (the ER*/HER2- group) were identified and included in the study. Survival outcomes were analysed using the Kaplan-Meier method. Results: The median follow-up time was 9.7 years after primary breast surgery. Ten-year distant disease-free survival (DDFS) was 84.0% in the HER2* group and 98.2% in the ER*/HER2- group (p < 0.001). Ten-year overall survival was only 78.5% in the HER2* group, but 91.7% in the ER*/HER2- group (p = 0.09). Conclusions: Cancer HER2 status is strongly associated with unfavourable DDFS during the first decade of follow-up in patients with small (pT1a-bN0M0) breast cancer when adjuvant anti-HER2-targeted treatment is not administered.

Comparison of vacuum-assisted excision (VAE) and breast lesion excision system (BLES) in the treatment of intraductal papillomas.

PURPOSE: This study aims to compare the feasibility of VAE and BLES in the treatment of intraductal papillomas. MATERIAL AND METHODS: Patients with a suspected intraductal papilloma who underwent a BLES or a VAE procedure were included in this retrospective study. The BLES procedures were performed between November 2011 and June 2016 and the VAE procedures between May 2018 and September 2020 at the Department of Radiology of Helsinki University Hospital (HUH). The procedures were performed with an intent of complete removal of the lesions. RESULTS: In total, 72 patients underwent 78 BLES procedures and 95 patients underwent 99 VAE procedures. Altogether 52 (60%) papillomas with or without atypia were completely removed with VAE, whereas 24 (46%) were completely removed with BLES, p = 0.115. The median radiological size of the high-risk lesions completely removed with BLES was 6 mm (4-12 mm), whereas with VAE it was 8 mm (3-22 mm), p = 0.016. Surgery was omitted in 90 (94.7%) non-malignant breast lesions treated with VAE and in 66 (90.4%) treated with BLES, p = 0.368. CONCLUSION: Both VAE and BLES were feasible in the treatment of intraductal papillomas. In most non-malignant lesions surgery was avoided, but VAE was feasible in larger lesions than BLES. However, follow-up ultrasound was needed more often after VAE. The histopathologic assessment is more reliable after BLES, as the lesion is removed as a single sample.

Falls in older aged adults in 22 European countries: incidence, mortality and burden of disease from 1990 to 2017.

INTRODUCTION: Falls in older aged adults are an important public health problem. Insight into differences in fall-related injury rates between countries can serve as important input for identifying and evaluating prevention strategies. The objectives of this study were to compare Global Burden of Disease (GBD) 2017 estimates on incidence, mortality and disability-adjusted life years (DALYs) due to fall-related injury in older adults across 22 countries in the Western European region and to examine changes over a 28-year period. METHODS: We performed a secondary database descriptive study using the GBD 2017 results on age-standardised fall-related injury in older adults aged 70 years and older in 22 countries from 1990 to 2017. RESULTS: In 2017, in the Western European region, 13 840 per 100 000 (uncertainty interval (UI) 11 837-16 113) older adults sought medical treatment for fall-related injury, ranging from 7594 per 100 000 (UI 6326-9032) in Greece to 19 796 per 100 000 (UI 15 536-24 233) in Norway. Since 1990, fall-related injury DALY rates showed little change for the whole region, but patterns varied widely between countries. Some countries (eg, Belgium and Netherlands) have lost their favourable positions due to an increasing fall-related injury burden of disease since 1990. CONCLUSIONS: From 1990 to 2017, there was considerable variation in fall-related injury incidence, mortality, DALY rates and its composites in the 22 countries in the Western European region. It may be useful to assess which fall prevention measures have been taken in countries that showed continuous low or decreasing incidence, death and DALY rates despite ageing of the population.

Global trends of hand and wrist trauma: a systematic analysis of fracture and digit amputation using the Global Burden of Disease 2017 Study.

BACKGROUND: As global rates of mortality decrease, rates of non-fatal injury have increased, particularly in low Socio-demographic Index (SDI) nations. We hypothesised this global pattern of non-fatal injury would be demonstrated in regard to bony hand and wrist trauma over the 27-year study period. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 was used to estimate prevalence, age-standardised incidence and years lived with disability for hand trauma in 195 countries from 1990 to 2017. Individual injuries included hand and wrist fractures, thumb amputations and non-thumb digit amputations. RESULTS: The global incidence of hand trauma has only modestly decreased since 1990. In 2017, the age-standardised incidence of hand and wrist fractures was 179 per 100 000 (95% uncertainty interval (UI) 146 to 217), whereas the less common injuries of thumb and non-thumb digit amputation were 24 (95% UI 17 to 34) and 56 (95% UI 43 to 74) per 100 000, respectively. Rates of injury vary greatly by region, and improvements have not been equally distributed. The highest burden of hand trauma is currently reported in high SDI countries. However, low-middle and middle SDI countries have increasing rates of hand trauma by as much at 25%. CONCLUSIONS: Certain regions are noted to have high rates of hand trauma over the study period. Low-middle and middle SDI countries, however, have demonstrated increasing rates of fracture and amputation over the last 27 years. This trend is concerning as access to quality and subspecialised surgical hand care is often limiting in these resource-limited regions.

Resection margins and local recurrences of impalpable breast cancer: Comparison between radioguided occult lesion localization (ROLL) and radioactive seed localization (RSL).

OBJECTIVES: The aim of this retrospective study is to compare surgical margins, reoperation rates and local recurrences after breast conserving surgery (BCS) using radioguided occult lesion localization (ROLL) or radioactive seed localization (RSL). MATERIALS AND METHODS: We reviewed 744 consecutive patients with impalpable primary invasive breast cancer who underwent BCS at Helsinki University Hospital between 2010 and 2012. ROLL was used in our unit until October 31st, 2011; from November 1st we changed localization method to RSL. RESULTS: 318 patients underwent ROLL and 426 RSL. Patients in the RSL group had more often multifocal (p = 0.013) tumours. No statistically significant differences were found regarding tumour size, specimen weight, histology or grade of tumours or lymph node status. 42 (5.6%) patients were reoperated because of insufficient margins, 13 (4.1%) in the ROLL group and 29 (6.8%) in the RSL group. The reoperation rate was not different between the groups either in the univariable analysis (p = 0.112) or in the multivariable binary logistic regression analysis (p = 0.204). Risk factors for reoperations were multifocality of the tumour (p < 0.001), extensive intraductal component (p < 0.001), larger tumour size (p = 0.011), and smaller specimen weight (p = 0.014). The median follow-up time in the ROLL group was 81 (8-94) months and 64 (3-73) months in the RSL group. The five-year local recurrence-free survival (LRFS) estimates for ROLL and RSL groups were 98.0% and 99.4%, respectively (log-rank test, p = 0.323). CONCLUSION: Reoperation rates and LRFS were comparable for ROLL and RSL in patients with impalpable breast cancer treated with BCS.

Resection margins and local recurrences in breast cancer: Comparison between conventional and oncoplastic breast conserving surgery.

BACKGROUND: This retrospective cohort study aims to compare surgical margins, reoperations and local recurrences after conventional or oncoplastic breast conservation surgery (BCS). Furthermore, we aim to investigate differences between various oncoplastic techniques. MATERIAL AND METHODS: We reviewed 1800 consecutive patients with primary invasive breast cancer (N = 1707) or ductal carcinoma in situ (N = 93) who underwent BCS at Helsinki University Hospital between 2010 and 2012. RESULTS: Conventional BCS was performed in 1189 (66.1%) patients, oncoplastic BCS in 611 (33.9%). Various oncoplastic techniques were used. Patients with oncoplastic BCS had more often multifocal (p < 0.001), larger (p < 0.001), palpable tumours (p < 0.001) with larger resection specimens (p < 0.001). The amount of resected tissue varied substantially depending on the oncoplastic technique. Patients treated with oncoplastic BCS were younger (p < 0.001) and their tumours were more aggressive according to histological grade (p < 0.001), T-stage (p < 0.001), Ki-67 (p < 0.001) and lymph node status (p < 0.001). There was no difference, however, in surgical margins (p = 0.578) or reoperation rates (p = 0.430) between the groups. A total of 152 (8.4%) patients were reoperated because of insufficient margins, 96 (8.1%) in the conventional, 56 (9.2%) in the oncoplastic BCS group. The median follow-up time was 75 (2-94) months. There was no difference in local recurrence-free survival between the conventional and oncoplastic BCS groups (log-rank test, p = 0.172). CONCLUSIONS: Oncoplastic BCS was used for larger, multifocal and more aggressive tumours. Nevertheless, no difference in reoperation rate or local recurrences were found. Oncoplastic BCS is as safe as conventional BCS enabling breast conserving for patients who otherwise were candidates for mastectomy.

Surgical treatment and prognosis of breast cancer in elderly - A population-based study.

BACKGROUND: The aim of this study was to investigate outcome of treatment in patients over 80 years of age with early breast cancer at the time of the diagnosis with special interest in surgical treatment. MATERIALS AND METHODS: Breast cancer patients older than 80 years of age, treated at the Breast Surgery Unit of Helsinki University Hospital in 2005-2010 were identified from electronic patient records. Patients were followed-up until the end of 2014. Patient and tumour characteristics, recurrences, co-morbidities and reasons for omission of surgery were collected from electronic patient records. Survival data was obtained from Finnish Cancer Registry. RESULTS: 446 patients were eligible for the study: 401 (90%) received surgery. The median follow-up time was 52 months. In the entire study population, local and regional recurrences/disease progression were diagnosed in 16 (3.6%) and 6 (1.3%) patients, respectively. The five-year overall survival was 50.6% in the surgical treatment and only 15.2% in non-surgical treatment group, p < 0.001. Also, the five-year breast cancer specific survival was significantly better in the patients with surgery, 82.0%, but 56.0% in the patients without surgery, p < 0.001. There was no mortality related to the surgery, but 122 (30%) patients died within three years from surgery. CONCLUSION: Surgical treatment rate was high. OS and BCSS were better in surgically treated elderly patients. Local and regional disease control was excellent, probably due to high rate of surgical treatment. Surgical treatment also seemed safe in this elderly patient population. However, surgical overtreatment was obvious in some patients.

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study.

BACKGROUND: The prognostic significance of isolated tumour cells (ITCs) in the sentinel nodes (SNs) is controversial in early breast cancer, and some centres have abandoned immunohistochemistry to detect ITCs. METHODS: Patients with unilateral pT1N0 breast cancer, operated between February 2001 and August 2005 at a university hospital were included in this prospective, population-based cohort study. Survival of 936 patients with or without isolated tumour cells (ITC) in their SNs were compared with the log-rank test and Cox regression analysis. RESULTS: Eight hundred sixty one (92.0%) patients were ITC-negative (pN0i-) and 75 (8.0%) ITC-positive (pN0i+). Patients with ITC-positive cancer received more frequently adjuvant systemic therapies than those with ITC-negative cancer. The median follow-up time was 9.5 years. Ten-year distant disease-free survival was 95.3% in the pN0i- group and 88.8% in the pN0i+ group (P = 0.013). ITCs were an independent prognostic factor in a Cox regression model (HR = 2.34, 95% CI 1.09-5.04; P = 0.029), together with tumour Ki-67 proliferation index and diameter. ITCs were associated with unfavourable overall survival (P = 0.005) and breast cancer-specific survival (P = 0.001). CONCLUSIONS: We conclude that presence of ITCs in the SNs is an adverse prognostic factor in early small node-negative breast cancer, and may be considered in the decision-making for adjuvant therapy.

Breast Lesion Excision System in the diagnosis and treatment of intraductal papillomas - A feasibility study.

OBJECTIVES: This study aims to evaluate the feasibility of Breast Lesion Excision System (BLES) in the treatment of intraductal papillomas. MATERIAL AND METHODS: All patients with a needle biopsy -based suspicion of an intraductal papilloma who consequently underwent a BLES procedure at Helsinki University Hospital between 2011 and 2016 were included in this retrospective study. The purpose of the BLES procedure was either to excise the entire lesion or in few cases to achieve better sampling. RESULTS: In total, 74 patients underwent 80 BLES procedures. Pathological diagnosis after the BLES biopsy confirmed an intraductal papilloma without atypia in 43 lesions, whereas 10 lesions were upgraded to high-risk lesions (HRL) with either atypical ductal hyperplasia or lobular carcinoma in situ. Five cases were upgraded to malignancy, two were invasive ductal carcinomas and three were ductal carcinoma in situ. Additionally, 18 lesions were diagnosed as other benign lesions. Four procedures failed. Complete excision with BLES was achieved in 19 out of 43 intraductal papillomas, 6 out of 10 HRL and two out of five malignant lesions. No major complications occurred. The BLES procedure was adequate in the management of the 71 breast lesions. CONCLUSION: The BLES procedure is an acceptable method for the management of small benign and high-risk breast lesions such as intraductal papillomas in selected patients. Thus, a great amount of diagnostic surgical biopsies can be avoided.

Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery.

Purpose Persistent pain after breast cancer surgery is a well-recognized problem, with moderate to severe pain affecting 15% to 20% of women at 1 year from surgery. Several risk factors for persistent pain have been recognized, but tools to identify high-risk patients and preventive interventions are missing. The aim was to develop a clinically applicable risk prediction tool. Methods The prediction models were developed and tested using three prospective data sets from Finland (n = 860), Denmark (n = 453), and Scotland (n = 231). Prediction models for persistent pain of moderate to severe intensity at 1 year postoperatively were developed by logistic regression analyses in the Finnish patient cohort. The models were tested in two independent cohorts from Denmark and Scotland by assessing the areas under the receiver operating characteristics curves (ROC-AUCs). The outcome variable was moderate to severe persistent pain at 1 year from surgery in the Finnish and Danish cohorts and at 9 months in the Scottish cohort. Results Moderate to severe persistent pain occurred in 13.5%, 13.9%, and 20.3% of the patients in the three studies, respectively. Preoperative pain in the operative area ( P < .001), high body mass index ( P = .039), axillary lymph node dissection ( P = .008), and more severe acute postoperative pain intensity at the seventh postoperative day ( P = .003) predicted persistent pain in the final prediction model, which performed well in the Danish (ROC-AUC, 0.739) and Scottish (ROC-AUC, 0.740) cohorts. At the 20% risk level, the model had 32.8% and 47.4% sensitivity and 94.4% and 82.4% specificity in the Danish and Scottish cohorts, respectively. Conclusion Our validated prediction models and an online risk calculator provide clinicians and researchers with a simple tool to screen for patients at high risk of developing persistent pain after breast cancer surgery.

Does expecting more pain make it more intense? Factors associated with the first week pain trajectories after breast cancer surgery.

The aim of this study was to identify clinical risk factors for unfavorable pain trajectories after breast cancer surgery, to better understand the association between pain expectation, psychological distress, and acute postoperative pain. This prospective study included 563 women treated for breast cancer. Psychological data included questionnaires for depressive symptoms and anxiety. Experimental pain tests for heat and cold were performed before surgery. The amount of oxycodone needed for satisfactory pain relief after surgery was recorded. Pain intensity in the area of operation before surgery and during the first postoperative week and expected intensity of postoperative pain were recorded using the Numerical Rating Scale (NRS 0-10). Pain trajectories were formed to describe both initial intensity (the intercept) and the direction of the pain path (the slope). Factors associated with higher initial pain intensity (the intercept) were the amount of oxycodone needed for adequate analgesia, psychological distress, type of axillary surgery, preoperative pain in the area of the operation, and expectation of postoperative pain. The higher the pain initially was, the faster it resolved over the week. Expectation of severe postoperative pain was associated with higher scores of both experimental and clinical pain intensity and psychological factors. The results confirm that acute pain after breast cancer surgery is a multidimensional phenomenon. Psychological distress, pain expectation, and the patients' report of preoperative pain in the area to be operated should be recognized before surgery. Patients having axillary clearance need more efficient analgesic approaches.

The quality of preoperative diagnostics and surgery and their impact on delays in breast cancer treatment - A population based study.

BACKGROUND AND OBJECTIVES: This study aims to clarify quality of breast cancer surgery in population-based setting. We aim to elucidate factors influencing waiting periods, and to evaluate the effect of hospital volume on surgical treatment policies. Special interest was given to diagnostic and surgical processes and their impact on waiting times. METHODS: All 1307 patients having primary breast cancer surgery at the Helsinki and Uusimaa Hospital District during 2010 were included in this retrospective study. RESULTS: Median waiting time for primary surgery was 24 days and significantly affected by additional imaging and diagnostic biopsies as well as hospital volume. Final rate of breast conserving surgery was surprisingly low, 51%, not affected by hospital volume, p = 0.781. Oncoplastic resection and immediate breast reconstruction (IBR) were performed more often in high volume units, p < 0.001. Quality of axillary surgery varied with unit size. Multiple operations, IBR and high volume unit were factors prolonging initiation of adjuvant treatment. CONCLUSION: Quality of preoperative diagnostics play a crucial role in minimizing the need of repeated imaging and biopsies as well as multiple operations. Positive impact of high-volume hospitals becomes evident when analyzing procedures requiring advanced surgical techniques. High-volume hospitals achieved better quality in axillary surgery.

International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases.

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.

Multi-institutional comparison of non-sentinel lymph node predictive tools in breast cancer patients with high predicted risk of further axillary metastasis.

Although axillary lymph node dissection (ALND) has been the standard intervention in breast cancer patients with sentinel lymph node (SLN) metastasis, only a small proportion of patients benefit from this operation, because most do not harbor additional metastases in the axilla. Several predictive tools have been constructed to identify patients with low risk of non-SLN metastasis who could be candidates for the omission of ALND. In the present work, predictive nomograms were used to predict a high (>50 %) risk of non-SLN metastasis in order to identify patients who would most probably benefit from further axillary treatment. Data of 1000 breast cancer patients with SLN metastasis and completion ALND from 5 institutions were tested in 4 nomograms. A subset of 313 patients with micrometastatic SLNs were also tested in 3 different nomograms devised for the micrometastatic population (the high risk cut-off being 20 %). Patients with a high predicted risk of non-SLN metastasis had higher rates of metastasis in the non-SLNs than patients with low predicted risk. The positive predictive values of the nomograms ranged from 44 % to 64 % with relevant inter-institutional variability. The nomograms for micrometastatic SLNs performed much better in identifying patients with low risk of non-SLN involvement than in high-risk-patients; for the latter, the positive predictive values ranged from 13 % to 20 %. The nomograms show inter-institutional differences in their predictive values and behave differently in different settings. They are worse in identifying high risk patients than low-risk ones, creating a need for new predictive models to identify high-risk patients.

International multicenter tool to predict the risk of nonsentinel node metastases in breast cancer.

BACKGROUND: Axillary treatment of breast cancer patients is undergoing a paradigm shift, as completion axillary lymph node dissections (ALNDs) are being questioned in the treatment of patients with tumor-positive sentinel nodes. This study aims to develop a novel multi-institutional predictive tool to calculate patient-specific risk of residual axillary disease after tumor-positive sentinel node biopsy. METHODS: Breast cancer patients with a tumor-positive sentinel node and a completion ALND from five European centers formed the original patient series (N = 1000). Statistically significant variables predicting nonsentinel node involvement were identified in logistic regression analysis. A multivariable predictive model was developed and validated by area under the receiver operating characteristics curve (AUC), first internally in 500 additional patients and then externally in 1068 patients from other centers. All statistical tests were two-sided. RESULTS: Nine tumor- and sentinel node-specific variables were identified as statistically significant factors predicting nonsentinel node involvement in logistic regression analysis. A resulting predictive model applied to the internal validation series resulted in an AUC of 0.714 (95% confidence interval [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719 (95% CI = 0.689 to 0.750). The model was well calibrated in the external validation series. CONCLUSIONS: We present a novel, international, multicenter, predictive tool to assess the risk of additional axillary metastases after tumor-positive sentinel node biopsy in breast cancer. The predictive model performed well in internal and external validation but needs to be further studied in each center before application to clinical use.