Gene expression profiles in clinically T1-2N0 ER+HER2- breast cancer patients treated with breast-conserving therapy: their added value in case sentinel lymph node biopsy is not performed.

PURPOSE: Omitting sentinel lymph node biopsy (SLNB) in breast cancer treatment results in patients with unknown positive nodal status and potential risk for systemic undertreatment. This study aimed to investigate whether gene expression profiles (GEPs) can lower this risk in cT1-2N0 ER+ HER2- breast cancer patients treated with BCT. METHODS: Patients were included if diagnosed between 2011 and 2017 with cT1-2N0 ER+ HER2- breast cancer, treated with BCT and SLNB, and in whom GEP was applied. Adjuvant chemotherapy recommendations based on clinical risk status (Dutch breast cancer guideline of 2020 versus PREDICT v2.1) with and without knowledge on SLNB outcome were compared to GEP outcome. We examined missing adjuvant chemotherapy indications, and the number of GEPs needed to identify one patient at risk for systemic undertreatment. RESULTS: Of 3585 patients, 2863 (79.9%) had pN0 and 722 (20.1%) pN + disease. Chemotherapy was recommended in 1354 (37.8% guideline-2020) and 1888 patients (52.7% PREDICT). Eliminating SLNB outcome (n = 722) resulted in omission of chemotherapy recommendation in 475 (35.1% guideline-2020) and 412 patients (21.8% PREDICT). GEP revealed genomic high risk in 126 (26.5% guideline-2020) and 82 patients (19.9% PREDICT) in case of omitted chemotherapy recommendation in the absence of SLNB. Extrapolated to the whole group, this concerns 3.5% and 2.3%, respectively, resulting in the need for 28-44 GEPs to identify one patient at risk for systemic undertreatment. CONCLUSION: If no SLNB is performed, clinical risk status according to the guideline of 2020 and PREDICT predicts a very low risk for systemic undertreatment. The number of GEPs needed to identify one patient at risk for undertreatment does not justify its standard use.

The QUILT study: quilting sutures in patients undergoing breast cancer surgery: a stepped wedge cluster randomized trial study.

BACKGROUND: Seroma is the most common complication following breast cancer surgery, with reported incidence up to 90%. Seroma causes patient discomfort, is associated with surgical site infections (SSI), often requires treatment and increases healthcare consumption. The quilting suture technique, in which the skin flaps are sutured to the pectoralis muscle, leads to a significant reduction of seroma with a decrease in the number of aspirations and surgical site infections. However, implementation is lagging due to unknown side effects, increase in operation time and cost effectiveness. Main objective of this study is to assess the impact of large scale implementation of the quilting suture technique in patients undergoing mastectomy and/or axillary lymph node dissection (ALND). METHODS: The QUILT study is a stepped wedge design study performed among nine teaching hospitals in the Netherlands. The study consists of nine steps, with each step one hospital will implement the quilting suture technique. Allocation of the order of implementation will be randomization-based. Primary outcome is 'textbook outcome', i.e.no wound complications, no re-admission, re-operation or unscheduled visit to the outpatient clinic and no increased use of postoperative analgesics. A total of 113 patients is required based on a sample size calculation. Secondary outcomes are shoulder function, cosmetic outcome, satisfaction with thoracic wall and health care consumption. Follow-up lasts for 6 months. DISCUSSION: This will be one of the first multicentre prospective studies in which quilting without postoperative wound drain is compared with conventional wound closure. We hypothesize that quilting is a simple technique to increase textbook outcome, enhance patient comfort and reduce health care consumption.

Relations between recurrence risk perceptions and fear of cancer recurrence in breast cancer survivors.

PURPOSE: This study aimed to: (1) determine the accuracy of Dutch breast cancer survivors' estimations of the locoregional recurrence risk (LRR); (2) examine which variables influence (the accuracy of) risk estimations, and risk appraisals; and (3) investigate the influence of the objective LRR risk (estimated using the INFLUENCE-nomogram), risk estimations and risk appraisals on fear of cancer recurrence (FCR). Findings of this study will inform clinicians on risk communication and can improve communication about FCR. METHODS: In a cross-sectional survey among 258 breast cancer survivors, women's recurrence risk estimations (in odds) and risk appraisals (in high/low), FCR, demographics and illness perceptions, about one year after surgery were measured and compared to the objective risk for LRRs estimated using the INFLUENCE-nomogram. RESULTS: Half of the women (54%) accurately estimated their LRR risk, 34% underestimated and 13% overestimated their risk. Risk estimations and risk appraisals were only moderately positively correlated (r = 0.58). Higher risk appraisals were associated with radiotherapy (r = 0.18) and having weaker cure beliefs (r = - 0.19). Younger age was associated with overestimation of risk (r = - 0.23). Recurrence risk estimations and risk appraisals were associated with more FCR (r = 0.29, r = 0.39). In regression, only risk appraisal contributed significantly to FCR. CONCLUSION: Although women were fairly accurate in recurrence risk estimations, it remains difficult to predict over- or underestimation. Recurrence risk estimations and risk appraisal are two different concepts which are both associated with FCR and should therefore be addressed in patient-provider communication.

The Quest for Outpatient Mastectomy in COVID-19 Era: Barriers and Facilitators.

Background: The rate of inpatient mastectomies remains high despite multiple studies reporting favourably on outpatient mastectomies. Outpatient mastectomies do not compromise quality of patient care and are more efficient than inpatient care. The objective of this study was to evaluate the feasibility of outpatient mastectomy. Materials and Methods: Implementation of an outpatient mastectomy program was evaluated in a retrospective study. All patients who underwent mastectomy between January 2019 and September 2021 were included. Results: 213 patients were enrolled in the study: 62.4% (n = 133) outpatient mastectomies versus 37.6% (n = 80) inpatient mastectomies. A steady rise in outpatient mastectomies was observed over time. The second quarter of 2020, coinciding with the first COVID-19 wave, showed a peak in outpatient mastectomies. The only significant barrier to outpatient mastectomy proved to be bilateral mastectomy. Unplanned return to care was observed in 27.8% of the outpatient versus 36.3% of the inpatient mastectomies (P=0.198); the reason for unplanned return of care was similar in both groups. Conclusions: Outpatient mastectomy is shown to be feasible and safe with a steady increase during the study period. A barrier to outpatient mastectomy was bilateral mastectomy. Incidence of unplanned return to care or complications did not differ significantly between the outpatient and inpatient cohorts.

Conditional local recurrence risk: the effect of event-free years in different subtypes of breast cancer.

BACKGROUND: After breast cancer treatment, follow-up consists of physical examination and mammography for at least 5 years, to detect local and regional recurrence. The risk of recurrence may decrease after event-free time. This study aims to determine the risk of local recurrence (LR) as a first event until 5 years after diagnosis, conditional on being event-free for 1, 2, 3 and 4 years. METHODS: From the Netherlands Cancer Registry, all M0 breast cancers diagnosed between 2005 and 2008 were included. LR risk was calculated with Kaplan-Meier analysis, overall and for different subtypes. Conditional LR (assuming x event-free years) was determined by selecting event-free patients at x years, and calculating their LR risk within 5 years after diagnosis. RESULTS: Five-year follow-up was available for 34,453 patients. Overall, five-year LR as a first event occurred in 3.0%. This risk varied for different subtypes and was highest for triple negative (6.8%) and lowest for ER+PR+Her2- (2.2%) tumors. After 1, 2, 3 and 4 event-free years, the average risk of LR before 5 years after diagnosis decreased from 3.0 to 2.4, 1.6, 1.0, and 0.6%. The risk decreased in all subtypes, the effect was most pronounced in subtypes with the highest baseline risk (ER-Her2+ and triple negative breast cancer). After three event-free years, LR risk in the next 2 years was 1% or less in all subtypes except triple negative (1.6%). CONCLUSION: The risk of 5-year LR as a first event was low and decreased with the number of event-free years. After three event-free years, the overall risk was 1%. This is reassuring to patients and also suggests that follow-up beyond 3 years may produce low yield of LR, both for individual patients and studies using LR as primary outcome. This can be used as a starting point to tailor follow-up to individual needs.

Minimally invasive breast cancer excision using the breast lesion excision system under ultrasound guidance.

PURPOSE: To assess the feasibility of completely excising small breast cancers using the automated, image-guided, single-pass radiofrequency-based breast lesion excision system (BLES) under ultrasound (US) guidance. METHODS: From February 2018 to July 2019, 22 patients diagnosed with invasive carcinomas ≤ 15 mm at US and mammography were enrolled in this prospective, multi-center, ethics board-approved study. Patients underwent breast MRI to verify lesion size. BLES-based excision and surgery were performed during the same procedure. Histopathology findings from the BLES procedure and surgery were compared, and total excision findings were assessed. RESULTS: Of the 22 patients, ten were excluded due to the lesion being > 15 mm and/or being multifocal at MRI, and one due to scheduling issues. The remaining 11 patients underwent BLES excision. Mean diameter of excised lesions at MRI was 11.8 mm (range 8.0-13.9 mm). BLES revealed ten (90.9%) invasive carcinomas of no special type, and one (9.1%) invasive lobular carcinoma. Histopathological results were identical for the needle biopsy, BLES, and surgical specimens for all lesions. None of the BLES excisions were adequate. Margins were usually compromised on both sides of the specimen, indicating that the excised volume was too small. Margin assessment was good for all BLES specimens. One technical complication occurred (retrieval of an empty BLES basket, specimen retrieved during subsequent surgery). CONCLUSIONS: BLES allows accurate diagnosis of small invasive breast carcinomas. However, BLES cannot be considered as a therapeutic device for small invasive breast carcinomas due to not achieving adequate excision.

Trends in pre-operative needle biopsy use in invasive breast cancer diagnosis: a Dutch nationwide population study.

INTRODUCTION: In recent decades, the use of pre-operative needle biopsy for breast cancer diagnosis has shifted. There is also an increased demand for availability of predictive factors. This study aims to quantify these changes. MATERIAL AND METHODS: From the Dutch nationwide pathology database (PALGA), all reports on breast cancer for five periods of 3 months between 1996 and 2016 were retrieved. Reports were categorised using automatic recognition of keywords. Classification was checked manually for the first 200 reports per period. The first 100 resected cases in each period underwent detailed investigation. RESULTS: For automatic analysis 34,639 reports were retrieved. Accuracy was 98% compared to manual assessment. Fine needle aspiration cytology (FNAC) decreased from 77% (1996) to 58% (2001), 34% (2006), 25% (2011), and 17% (2016). For detailed assessment, 498 cases were analysed. Diagnostic surgical excision decreased from 24% in 1996 to 3% in 2016, cases with only cytology from 65% to 1%, respectively. Cytology and core needle biopsy (CNB) were combined in 21% of cases in 2016. Pre-operative availability of ER status increased from 3% in 1996 to 36% in 2006 and 78% in 2016 (as compared to 47%, 92%, and 97% for post-operative availability, respectively) and for HER2 status from 0% to 13% and 66% (as compared to 1%, 89%, and 96% for post-operative availability, respectively). CONCLUSION: Results suggest that nationwide, clinics prioritise reliability and availability of ER and HER2 status, replacing FNAC by CNB. However, for optimal treatment planning for all patients, availability of pre-operative receptor status warrants further improvement.

Metastatic behavior and overall survival according to breast cancer subtypes in stage IV inflammatory breast cancer.

BACKGROUND: Distant metastatic disease is frequently observed in inflammatory breast cancer (IBC), with a poor prognosis as a consequence. The aim of this study was to analyze the association of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) based breast cancer subtypes in stage IV inflammatory breast cancer (IBC) with preferential site of distant metastases and overall survival (OS). METHODS: For patients with stage IV IBC, diagnosed in the Netherlands between 2005 and 2016, tumors were classified into four breast cancer subtypes: HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. Patient, tumor, and treatment characteristics and sites of metastases were compared. OS of the subtypes was compared using Kaplan-Meier curves and the log-rank test. Association between subtype and OS was assessed in multivariable models using logistic regression. RESULTS: In total, 744 eligible patients were included: 340 (45.7%) tumors were HR+/HER2-, 148 (19.9%) HR-/HER2+, 131 (17.6%) HR+/HER2+, and 125 (16.8%) HR-/HER2-. Bone was the most common metastatic site in all subtypes. A significant predominance of bone metastases was found in HR+/HER2- IBC (71.5%), and liver and lung metastases in the HR-/HER2+ (41.2%) and HR-/HER2- (40.8%) subtypes, respectively. In multivariable analysis, the HR-/HER2- subtype was associated with significantly worse OS as compared to the other subtypes. CONCLUSION: Breast cancer subtypes in stage IV IBC are associated with distinct patterns of metastatic spread and display notable differences in OS. The use of breast cancer subtypes can guide a more patient-tailored staging directed to metastatic site and extend of disease.

Omitting Postoperative Wound Drainage After Mastectomy With Skin-Flap Quilting.

BACKGROUND: Seroma is the most frequent complication after mastectomy (ME) and axillary lymph node dissection (ALND). The quilting suture technique, in which skin flaps are sutured to the underlying muscle, was previously investigated and found to reduce seroma incidence after ME and ALND. This study aimed to investigate whether postoperative wound drainage can safely be omitted when quilting sutures are applied. METHODS: Two groups with a total of 251 consecutive patients who underwent ME, ALND, or both were retrospectively compared. The first group underwent quilting sutures with wound vacuum drainage, and the second group underwent quilting sutures without wound drainage. The primary outcome was the incidence of postoperative clinically significant seroma (CSS). The secondary outcomes were the incidence of postoperative infection, bleeding complications, wound dehiscence, and flap necrosis. RESULTS: The group without a postoperative drain (n = 166) had a significantly lower CSS incidence (8.4%) than the group with a postoperative drain (n = 85, 21.2%) (p < 0.05). In the multivariate analysis, no significant predictors were found for seroma formation. Wound complications significantly decreased, from 31.8% in the group with a drain group to 17.5% in the group without a drain (p < 0.05). CONCLUSION: This study showed that the postoperative drain can be omitted when quilting sutures are applied in ME, ALND, or both. This facilitates day care mastectomy, eliminating drain-related care, discomfort, and related expenses.

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.

Patterns and predictors of first and subsequent recurrence in women with early breast cancer.

PURPOSE: Little is known about the occurrence, timing and prognostic factors for first and also subsequent local (LR), regional (RR) or distant (DM) breast cancer recurrence. As current follow-up is still consensus-based, more information on the patterns and predictors of subsequent recurrences can inform more personalized follow-up decisions. METHODS: Women diagnosed with stage I-III invasive breast cancer who were treated with curative intent were selected from the Netherlands Cancer Registry (N = 9342). Extended Cox regression was used to model the hazard of recurrence over ten years of follow-up for not only site-specific first, but also subsequent recurrences after LR or RR. RESULTS: In total, 362 patients had LR, 148 RR and 1343 DM as first recurrence. The risk of first recurrence was highest during the second year post-diagnosis (3.9%; 95% CI 3.5-4.3) with similar patterns for LR, RR and DM. Young age (<40), tumour size >2 cm, tumour grade II/III, positive lymph nodes, multifocality and no chemotherapy were prognostic factors for first recurrence. The risk of developing a second recurrence after LR or RR (N = 176) was significantly higher after RR than after LR (50 vs 29%; p < 0.001). After a second LR or RR, more than half of the women were diagnosed with a third recurrence. CONCLUSIONS: Although the risk of subsequent recurrence is high, absolute incidence remains low. Also, almost half the second recurrences are detected in the first year after previous recurrence and more than 80% are DM. This suggests that more intensive follow-up for early detection subsequent recurrence is not likely to be (cost-)effective.

Performance characteristics of specimen radiography for margin assessment for ductal carcinoma in situ: a systematic review.

BACKGROUND: Reducing positive margin rate (PMR) and reoperation rate in breast-conserving operations remains a challenge, mainly regarding ductal carcinoma in situ (DCIS). Intra-operative margin assessment tools have emerged to reduce PMR over the last decades, including specimen radiography (SR). No consensus has been reached on the reliability and efficacy of SR in DCIS. OBJECTIVE: We performed a systematic literature review to assess the performance characteristics of SR for margin assessment of breast lesions with pure DCIS and invasive cancers with DCIS components. METHODS: A literature search was conducted for diagnostic studies up to April 2017 concerning SR for intra-operative margin assessment of breast lesions with pure DCIS or with DCIS components. Studies reporting sensitivity and specificity calculated using final pathology report as reference test were included. Due to improved imaging technology, studies published more than 15 years ago were excluded. Methodological quality was assessed using quality assessment of diagnostic accuracy studies-2 checklist. Due to clinical and methodological diversity, meta-analysis was considered not useful. RESULTS: Of 235 citations identified, 9 met predefined inclusion criteria and documented diagnostic efficacy data. Sensitivity ranged from 22 to 77% and specificity ranged from 51 to 100%. Positive predictive value and negative predictive value ranged from 53 to 100% and 32 to 95%, respectively. High or unclear risk of bias was found in reference standard in 5 of 9 studies. High concerns regarding applicability of index test were found in 6 of 9 studies. CONCLUSIONS: The present results do not support the routine use of intra-operative specimen radiography to reduce the rate of positive margins in patients undergoing breast-conserving surgery for pure DCIS or the DCIS component in invasive cancer. Future studies need to differentiate between initial and final specimen margin involvement. This could provide surgeons with a number needed to treat for a more applicable outcome.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

BACKGROUND: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. METHODS: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. DISCUSSION: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. TRIAL REGISTRATION: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Breast-conserving therapy versus mastectomy in T1-2N2 stage breast cancer: a population-based study on 10-year overall, relative, and distant metastasis-free survival in 3071 patients.

PURPOSE: Our previous study demonstrated breast-conserving surgery with radiation therapy (BCT) to be at least equivalent to mastectomy in T1-2N0-1 breast cancer. Yet, 10-year survival rates after BCT and mastectomy with radiation therapy (MAST) in T1-2N2 breast cancer specifically have not been examined. Our study aimed to determine 10-year overall (OS), relative (RS), and distant metastasis-free survival (DMFS) in T1-2N2 breast cancer after BCT and MAST, stratified for T category. METHODS: All women diagnosed with primary invasive T1-2N2 breast cancer in 2000-2004, treated with BCT or MAST, both with axillary dissection and RT, were selected from the Netherlands Cancer Registry. Ten-year OS and DMFS were estimated using multivariable Cox regression. Excess mortality ratios (EMR) were calculated to estimate RS, using life tables of the general population. OS and RS were determined on the whole cohort, and DMFS on the 2003 cohort with completed follow-up. Missing data were imputed. RESULTS: Of 3071 patients, 1055 (34.4 %) received BCT and 2016 (65.7 %) MAST. BCT and MAST showed equal 10-year OS and RS. After stratification, BCT was significantly associated with improved 10-year OS [HRadjusted 0.82 (95 % CI 0.71-0.96)] and RS (EMRadjusted 0.81 (95 % CI 0.67-0.97]) in T2N2, but not in T1N2. Ten-year DMFS was equal for both treatments [HRadjusted 0.87 (95 % CI 0.64-1.18)] in the 2003 cohort (n = 594), which was representative for the full cohort. CONCLUSION: BCT showed at least equal 10-year OS, RS, and DMFS compared to MAST. These results confirm that BCT is a good treatment option in T1-2N2 breast cancer.

Sentinel lymph node biopsy can be omitted in DCIS patients treated with breast conserving therapy.

Breast cancer guidelines advise sentinel lymph node biopsy (SLNB) in patients with ductal carcinoma in situ (DCIS) on core biopsy at high risk of invasive cancer or in case of mastectomy. This study investigates the incidence of SLNB and SLN metastases and the relevance of indications in guidelines and literature to perform SLNB in order to validate whether SLNB is justified in patients with DCIS on core biopsy in current era. Clinically node negative patients diagnosed from 2004 to 2013 with only DCIS on core needle biopsy were selected from a national database. Incidence of SLN biopsy and metastases was calculated. With Fisher exact tests correlation between SLNB indications and actual presence of SLN metastases was studied. Further, underestimation rate for invasive cancer and correlation with SLN metastases was analysed. 910 patients were included. SLNB was performed in 471 patients (51.8 %): 94.5 % had pN0, 3.0 % pN1mi and 2.5 % pN1. Patients undergoing mastectomy had 7 % SLN metastases versus 3.5 % for breast conserving surgery (BCS) (p = 0.107). The only factors correlating to SLN metastases were smaller core needle size (p = 0.01) and invasive cancer (p < 0.001). Invasive cancer was detected in 16.7 % by histopathology with 15.6 % SLN metastases versus only 2 % in pure DCIS. SLNB showed metastases in 5.5 % of patients; 3.5 % in case of BCS (any histopathology) and 2 % when pure DCIS was found at definitive histopathology (BCS and mastectomy). Consequently, SLNB should no longer be performed in patients diagnosed with DCIS on core biopsy undergoing BCS. If definitive histopathology shows invasive cancer, SLNB can still be considered after initial surgery.

Meta-analysis of ultrasound-guided biopsy of suspicious axillary lymph nodes in the selection of patients with extensive axillary tumour burden in breast cancer.

BACKGROUND: Recent studies show that not all patients with breast cancer and positive axillary lymph nodes need additional axillary surgery. A systematic review and meta-analysis of the literature was performed to test the hypothesis that ultrasound-guided biopsy of suspicious nodes can be a useful tool to identify patients with extensive axillary tumour burden. METHODS: PubMed and Embase were searched to identify articles reporting on ultrasound-guided techniques to stage the axilla of patients with breast cancer. The emphasis was to study the number of positive nodes found after axillary lymph node dissection (ALND) following a positive ultrasound-guided biopsy or a positive sentinel lymph node biopsy (SLNB). Information regarding the number of positive nodes thus had to be available. Results were tested for heterogeneity and a meta-analysis was performed. RESULTS: A total of 894 articles were identified, and 115 were selected based on title and abstract information by two independent reviewers. After extensive review, 18 articles were eligible for analysis. Eight studies reported sufficient data to perform a meta-analysis comparing 532 patients with a positive ultrasound-guided biopsy with 248 patients with a negative ultrasound-guided biopsy but a positive SLNB. The number of involved nodes was significantly higher in patients in whom axillary metastasis was detected by ultrasound-guided biopsy (P < 0·001). No heterogeneity in the observed effect was found (I(2) = 22 per cent, P = 0·26). CONCLUSION: Patients with breast cancer in whom axillary metastases are detected by ultrasound-guided biopsy have significantly more involved nodes than SLNB-positive patients. This finding enables further preoperative tailoring of axillary treatment in breast cancer.

The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07).

BACKGROUND: Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. DESIGN: This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. DISCUSSION: We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. TRIAL REGISTRATION: The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .

Inconsistent selection and definition of local and regional endpoints in breast cancer research.

BACKGROUND: Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined. METHODS: PubMed was searched for breast cancer studies published in nine leading journals in 2011. Articles using endpoints with a local or regional component were included and definitions were compared. RESULTS: Twenty-three different endpoints with a local or regional component were extracted from 44 articles. Most frequently used were disease-free survival (25 articles), recurrence-free survival (7), local control (4), locoregional recurrence-free survival (3) and event-free survival (3). Different endpoints were used for similar outcomes. Of 23 endpoints, five were not defined and 18 were defined only partially. Of these, 16 contained a local and 13 a regional component. Included events were not specified in 33 of 57 (local) and 27 of 50 (regional) cases. Definitions of local components inconsistently included carcinoma in situ and skin and chest wall recurrences. Regional components inconsistently included specific nodal sites and skin and chest wall recurrences. CONCLUSION: Breast cancer studies use many different endpoints with a locoregional component. Definitions of endpoints and events are either not provided or vary between trials. To improve transparency, facilitate trial comparison and avoid unjustified conclusions, authors should report detailed definitions of all endpoints.

Acute abdomen as the first presentation of a malignant lymphoma of the small intestine.

Malignant small intestinal lymphoma is a quite rare disease that often has an atypical presentation with symptoms of abdominal pain, nausea and weight loss. However, as illustrated in the following cases, acute abdomen due to an intestinal perforation can be the first sign of malignant lymphoma.

Quality assurance of radiation therapy after breast-conserving surgery among patients in the BOOG 2013-08 trial.

BACKGROUND AND PURPOSE: In the BOOG 2013-08 trial (NCT02271828), cT1-2N0 breast cancer patients were randomized between breast conserving surgery with or without sentinel lymph node biopsy (SLNB) followed by whole breast radiotherapy (WBRT). While awaiting primary endpoint results (axillary recurrence rate), this study aims to perform a quality assurance analysis on protocol adherence and (incidental) axillary radiation therapy (RT) dose. MATERIALS AND METHODS: Patients were enrolled between 2015 and 2022. Data on prescribed RT and (in 25% of included patients) planning target volumes (PTV) parameters were recorded for axillary levels I-IV and compared between treatment arms. Multivariable linear regression analysis was performed to determine prognostic variables for incidental axillary RT dose. RESULTS: 1,439/1,461 included patients (98.5%) were treated according to protocol and 87 patients (5.9%) received regional RT (SLNB 10.9%, no-SLNB 1.5 %). In 326 patients included in the subgroup analysis, the mean incidental PTV dose at axilla level I was 59.5% of the prescribed breast RT dose. In 5 patients (1.5%) the mean PTV dose at level I was ≥95% of the prescribed breast dose. No statistically or clinically significant differences regarding incidental axillary RT dose were found between treatment arms. Tumour bed boost (yes/no) was associated with a higher incidental mean dose in level I (R2 = 0.035, F(6, 263) = 1.532, p 0.168). CONCLUSION: The results indicate that RT-protocol adherence was high, and that incidental axillary RT dose was low in the BOOG 2013-08 trial. Potential differences between treatmentarms regarding the primary endpoint can thus not be attributed to different axillary radiation doses.