The effect of breast MRI on disease-free and overall survival in breast cancer patients: a retrospective population-based study.

PURPOSE: To evaluate the effect of breast MRI on overall survival (OS) and disease-free survival (DFS) of patients with invasive breast cancer in the Netherlands. METHODS: We selected all women from the Netherlands Cancer Registry diagnosed with invasive breast cancer (a) between 2011 and 2013 for the OS-cohort and (b) in the first quarter of 2012 for the DFS-cohort. The study population was subdivided into an MRI and non-MRI group. In addition, subgroups were created according to breast cancer subtype: invasive carcinoma of no special type (NST) versus invasive lobular carcinoma (ILC). OS and DFS were compared between the MRI and non-MRI group using the Kaplan-Meier method and the log-rank test. Cox proportional hazard regression analysis was performed to estimate hazard ratios (HR) with a 95% confidence interval (CI). To account for missing data, multiple imputation was performed. RESULTS: Of the 31,756 patients included in the OS-cohort (70% non-MRI and 30% MRI), 27,752 (87%) were diagnosed with invasive carcinoma NST and 4004 (13%) with ILC. Of the 2464 patients included in the DFS-cohort (72% non-MRI and 28% MRI), 2161 (88%) were diagnosed with invasive carcinoma NST and 303 (12%) with ILC. The distribution of breast MRI use was significantly lower over different age categories, from 49.0% aged < 50 to 16.5% aged > 70. Multivariable Cox regression showed that breast MRI was not significantly associated with OS overall (HR 0.91, 95%-CI 0.74-1.11, p = 0.35), nor in the different histological subtypes. Multivariable Cox regression analysis showed that breast MRI was also not significantly associated with DFS (HR 1.16, 95%-CI 0.81-1.67), nor in the different histological subtypes. CONCLUSION: Use of breast MRI was not significantly associated with an improved OS or DFS in patients treated with primary surgery.

Prognostic impact of repeat sentinel lymph node biopsy in patients with ipsilateral breast tumour recurrence.

BACKGROUND: Ipsilateral breast tumour recurrence (IBTR) has an unfavourable prognosis, with a significant subsequent risk of distant recurrence. Repeat sentinel lymph node biopsy (rSLNB) has recently been demonstrated to be technically feasible and useful in tailoring adjuvant treatment plans in patients with IBTR. The prognostic impact of rSLNB in patients with IBTR remains unclear. This study analysed the risk of distant recurrence after IBTR, and evaluated the prognostic impact of rSLNB and other patient and tumour characteristics on distant recurrence-free survival. METHODS: Data were obtained from the SNARB (Sentinel Node and Recurrent Breast Cancer) study. Cox proportional hazards analyses were performed to assess the prognostic effect of tumour, patient and treatment factors on distant recurrence-free survival. RESULTS: Of the 515 included patients, 230 (44·7 per cent) had a tumour-negative rSLNB and 46 (8·9 per cent) a tumour-positive rSLNB. In 239 patients (46·4 per cent) the rSLNB procedure was unsuccessful. After a median follow-up of 5·1 years, 115 patients (22·3 per cent) had developed a recurrence. The overall 5-year distant recurrence-free survival rate was 84·2 (95 per cent c.i. 80·7 to 87·7) per cent. An interval of less than 2 years between primary breast cancer treatment and ipsilateral recurrence (P = 0·018), triple-negative IBTR (P = 0·045) and absence of adjuvant chemotherapy after IBTR (P = 0·010) were independently associated with poor distant recurrence-free survival. The association between the outcome of rSLNB and distant recurrence-free survival was not statistically significant (P = 0·682). CONCLUSION: The outcome of rSLNB is not an important prognostic factor for distant recurrence, and its value as a staging tool in patients with IBTR seems disputable.

Population-based study of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ.

BACKGROUND: Determinants of the use of breast MRI in patients with ductal carcinoma in situ (DCIS) in the Netherlands were studied, and whether using MRI influenced the rates of positive resection margins and mastectomies. METHODS: All women aged less than 75 years, and diagnosed with DCIS between 2011 and 2015, were identified from the Netherlands Cancer Registry. Multivariable logistic regression analyses were performed, adjusting for incidence year, age, hospital type, DCIS grade and multifocality. RESULTS: Breast MRI was performed in 2382 of 10 415 DCIS cases (22·9 per cent). In multivariable analysis, patients aged less than 50 years, those with high- or intermediate-grade DCIS and patients with multifocal disease were significantly more likely to have preoperative MRI. Patients undergoing MRI were more likely to have a mastectomy, either as first surgical treatment or following breast-conserving surgery (BCS) in the event of positive margins (odds ratio (OR) 2·11, 95 per cent c.i. 1·91 to 2·33). The risk of positive surgical margins after BCS was similar for those with versus without MRI. The secondary mastectomy rate after BCS was higher in patients who had MRI, especially in women aged less than 50 years (OR 1·94, 1·31 to 2·89). All findings were similar for low- and intermediate/high-grade DCIS. CONCLUSION: Adding MRI to conventional breast imaging did not improve surgical outcome in patients diagnosed with primary DCIS. The likelihood of undergoing a mastectomy was twice as high in the MRI group, and no reduction in the risk of margin involvement was observed after BCS.

ANTECEDENTES: Se estudiaron los determinantes del uso de la resonancia magnética (RM) de mama en pacientes con carcinoma ductal in situ (ductal carcinoma in situ, DCIS) en los Países Bajos y si el uso de la RM influía en las tasas de márgenes de resección positivos y de mastectomías. MÉTODOS: Todas las mujeres menores de 76 años de edad y diagnosticadas de DCIS fueron identificadas a partir del Registro de Cáncer de los Países Bajos de 2011-2015. Se realizaron análisis de regresión logística multivariable, ajustando por año de incidencia, edad, tipo de hospital, grado de DCIS y multifocalidad. RESULTADOS: Se realizó una RM de mama en 2.382 de 10.415 (23%) pacientes con DCIS. En el análisis multivariable, en las pacientes de edad < 50 años, con DCIS de grado alto o intermedio y enfermedad multifocal era estadísticamente significativo más probable que se sometieran a una RM preoperatoria. Las pacientes que se sometieron a RM tuvieron más probabilidades de que se efectuara una mastectomía, ya fuera como primer tratamiento quirúrgico o después de una cirugía conservadora de mama (breast conserving surgery, BCS) en el caso de presentar márgenes positivos (razón de oportunidades, odds ratio, OR = 2,1, i.c. del 95%: 1,9-2,3). El riesgo de obtener márgenes quirúrgicos positivos después de la BCS fue similar para aquellas pacientes con RM versus sin RM. Sin embargo, la tasa de mastectomía secundaria después de la BCS fue mayor en pacientes con RM, especialmente en mujeres menores de 50 años (OR = 1,9, i.c. del 95%: 1,3-2,9). CONCLUSIÓN: Agregar la RM a las imágenes radiológicas convencionales de mama no mejoró el resultado quirúrgico en pacientes diagnosticadas de DCIS primario. En el grupo de RM, la probabilidad de someterse a una mastectomía fue dos veces más alta, sin observarse una reducción en el riesgo de afectación del margen después de la BCS.

Non-visualized sentinel nodes in breast cancer patients; prevalence, risk factors, and prognosis.

BACKGROUND: Evidence and consensus is lacking in international guidelines regarding axillary treatment recommendations for patients in whom a sentinel lymph node (SLN) cannot be visualized (non-vSLN) during the sentinel node procedure. In this study we aimed to determine the prevalence of non-vSLNs in a Dutch population of breast cancer patients and to examine predictors and survival rate for non-vSLN. METHODS: A nationwide, retrospective, population-based study was performed including 116,920 patients with invasive breast cancer who underwent a SLN procedure in the Netherlands between January 2005 and December 2013. RESULTS: Of the 76,472 clinically negative patients who underwent a SLN procedure, 1924 patients (2.5%) had a non-vSLN, of whom 1552 (80.7%) underwent an ALND. Multivariate analysis showed predictive factors for non-vSLN: older age (p < 0.001), diagnosis in the period 2005-2009 (p < 0.001), larger tumor size (p = 0.003), and extensive nodal involvement (p < 0.001). Multivariate survival analysis showed a significantly worse survival (HR 1.18, 95% CI 1.03-1.34, p = 0.015) for non-vSLNs patients. However, in the non-vSLN group, an ALND was not statistically significantly associated with a better survival (HR 0.96, 95% CI 0.53-1.75, p = 0.891). CONCLUSION: Patients with non-vSLNs had less favorable disease characteristics and a worse survival compared to patients with a visualized SLN. Performing an ALND was not associated with a significantly better survival in patients with non-vSLNs. However, further research on the necessity of axillary treatment in this specific patient group is required.

In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium.

BACKGROUND: The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. PATIENTS AND METHODS: All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan-Meier method and compared using the log-rank test. RESULTS: From the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2-6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3-15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors. CONCLUSIONS: A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors.

Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in Invasive Lobular Versus Ductal Breast Cancer.

BACKGROUND: This study was conducted to determine the impact of neoadjuvant chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed for patients with invasive lobular breast carcinoma (ILC) and invasive ductal carcinoma (IDC). METHODS: Female patients with a diagnosis of ILC or IDC in The Netherlands between July 2008 and December 2012 were identified through the population-based Netherlands Cancer Registry. RESULTS: A total of 466 ILC patients received NAC compared with 3622 IDC patients. Downstaging by NAC was seen in 49.7 % of the patients with ILC and in 69.6 % of the patients with IDC, and a pathologic complete response (pCR) was observed in 4.9 and 20.2 % of these patients, respectively (P < 0.0001). Breast-conserving surgery was performed for 24.4 % of the patients with ILC receiving NAC versus 39.4 % of the patients with IDC. In the ILC group, 8.2 % of the patients needed surgical reinterventions after BCS due to tumor-positive resection margins compared with 3.4 % of the patients with IDC (P < 0.0001). Lobular histology was independently associated with a higher mastectomy rate (odds ratio 1.91; 95 % confidence interval 1.49-2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more often when NAC was administered in ILC as well as IDC. CONCLUSION: The patients with ILC receiving NAC were less likely to experience a pCR and less likely to undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for ILC patients was lower than for patients receiving surgery without NAC. However, despite the high number to treating in order to achieve BCS, a small subset of ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.

Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer?

BACKGROUND: We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients. METHODS: Consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy. RESULTS: Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI <24 months and 485 patients with MFI >24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI <24 months (median 29.4 vs 9.1 months, P<0.0001), but no difference in survival compared with patients with recurrent metastatic breast cancer with MFI >24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI <24 months had increased mortality risk (hazard ratio 1.97, 95% CI 1.49-2.60, P<0.0001) compared with patients with de novo metastatic breast cancer. When comparing recurrent metastatic breast cancer with MFI >24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy. CONCLUSION: Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI <24 months, irrespective of the use of prior adjuvant systemic therapy in the latter group. However, compared with patients with MFI >24 months, patients with de novo metastatic breast cancer had similar outcome.

Repeat sentinel node biopsy should be considered in patients with locally recurrent breast cancer.

Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non-metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %; P < 0.001). In 230 patients (80.1 %), the retrieved SN was tumor negative; 17 SNs (5.9 %) contained a micrometastasis and 29 (10.1 %) a macrometastasis. Confirmation ALND in 31 repeat SN-negative patients revealed a macrometastasis in two patients (6.5 %). The negative predictive value (NPV) of repeat SNB was 93.6 %, and ALND was omitted in 109 of the 248 patients (44.0 %) with a negative repeat SN. In 29 of the 44 patients (63.0 %) with a positive SN, adjuvant treatment plans were altered based on the repeat SNB. Repeat SNB is a feasible procedure with a high NPV, leading to a change in management in a substantial proportion of patients. Therefore, repeat SNB should replace routine ALND and serve as the standard of care in recurrent breast cancer.

The role of ultrasound-guided lymph node biopsy in axillary staging of invasive breast cancer in the post-ACOSOG Z0011 trial era.

BACKGROUND: Axillary status in invasive breast cancer, established by sentinel lymph node biopsy (SLNB) or ultrasound-guided lymph node biopsy, is an important prognostic indicator. The ACOSOG Z0011 trial showed that axillary dissection may be redundant in selected sentinel node-positive patients, raising questions on the applicability of these conclusions on ultrasound positive patients. The purpose of this study was to evaluate potential differences in patient and tumor characteristics and survival between axillary node positive patients after ultrasound (US group) or sentinel lymph node procedure (SN group). METHODS: Patients diagnosed with invasive breast cancer at the Máxima Medical Center between January 2006 and December 2011 were studied. RESULTS: In total, 302 node-positive cases were included: 139 and 163 cases in the US and SN groups, respectively. Patients in the US group were older at diagnosis (p < 0.001), more often had palpable nodes (p < 0.001), mastectomy (p < 0.001), larger tumors (p < 0.001), higher tumor grade (p = 0.001), lymphovascular invasion (p = 0.035), a positive Her2Neu (p = 0.006), and a negative hormonal receptor status (p = 0.003). Also, they were more likely to have more lymph nodes with macrometastases (p < 0.001), extranodal extension (p < 0.001), and involvement of level-III-lymph node (p < 0.001). Finally, they showed a worse disease-free survival [hazard ratio (HR) = 2.71; 95 % confidence interval (CI) = 1.49-4.92] and overall survival (HR = 2.67; 95 % CI = 1.48-4.84) than the SN group. CONCLUSIONS: These results suggest that ultrasound-positive patients have less favorable disease characteristics and a worse prognosis than SN-positive patients. Therefore, we conclude that omitting an ALND is as yet only applicable, as concluded in the Z0011, in patients with a positive SLNB.

Patients with invasive lobular breast cancer are less likely to undergo breast-conserving surgery: a population based study in the Netherlands.

PURPOSE: The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC). METHODS: Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from the NCR. All patients underwent BCS or primary mastectomy without neoadjuvant treatment and proportions per year were calculated. Logistic regression analysis with adjustment for period, age, nodal status and tumor size was performed to determine the impact of histology on the likelihood of undergoing BCS. RESULTS: A total of 152,574 patients underwent surgery in the period between 1990 and 2010, of which 89 % had IDC and 11 % had ILC. In the group of IDC with pT1 and pT2 tumors combined, 54 % underwent BCS compared with 43 % of patients with ILC (p < 0.0001). The proportion of patients with IDC treated by BCS increased from 46 % in 1990 to 62 % in 2010. The BCS rate among ILC patients increased from 39 % in 1990 to 48 % in 2010. Patients with ILC were less likely to undergo BCS compared with patients with IDC (odds ratio 0.69; 95 % confidence interval 0.66-0.71). CONCLUSION: The incidence of BCS for patients with IDC or ILC is rising in The Netherlands. However, the increase of BCS is less explicit in patients with ILC, with a higher chance of undergoing mastectomy compared with patients with IDC.

Improving the Success Rate of Repeat Sentinel Node Biopsy in Recurrent Breast Cancer.

PURPOSE: Repeat sentinel node biopsy (SNB) is an alternative to axillary lymph node dissection (ALND) for axillary staging in recurrent breast cancer. This study was conducted to determine factors associated with technical success of repeat SNB. METHODS: A total of 536 patients with locally recurrent nonmetastatic breast cancer underwent lymphatic mapping (LM) and repeat SNB in 29 Dutch hospitals. RESULTS: A total of 179 patients previously underwent breast-conserving surgery (BCS) with SNB, 262 patients BCS with ALND and 61 patients mastectomy, 35 with SNB and 26 with ALND. Another 34 patients underwent breast surgery without axillary interventions. A repeat sentinel node (SN) was identified in 333 patients (62.1 %) and was successfully removed in 235 (53.5 %). The overall repeat SN identification rate was 62.1 %, varying from 35 to 100 % in the participating hospitals. Previous radiotherapy of the breast [odds ratio (OR) 0.16; 95 % confidence interval (CI) 0.03-0.84], subareolar tracer injection (OR 0.34; 95 % CI 0.16-0.73), and a 2-day LM protocol (OR 0.57; 95 % CI 0.33-0.97) after previous BCS were independently associated with failure of SN identification. Injection of a larger amount of tracer (>180 MBq) led to a higher identification rate (OR 4.40; 95 % CI 1.45-13.32). CONCLUSIONS: Repeat SNB is a technically feasible procedure for axillary staging in recurrent breast cancer patients. Previous radiotherapy appears to be associated with failure of SN identification. Injection with a larger amount of tracer (>180 MBq) leads to a higher identification rate; subareolar injection and a 2-day LM protocol after previous BCS appear to be less adequate.

Iodine seed- versus wire-guided localization in breast-conserving surgery for non-palpable ductal carcinoma in situ.

BACKGROUND: Breast-conserving surgery for isolated non-palpable ductal carcinoma in situ (DCIS) is associated with high rates of incomplete surgical resection in comparison with unifocal invasive breast cancer. Therefore, accurate preoperative localization of the lesion is very important to facilitate adequate resection. Wire-guided localization (WGL) remains the standard for localization of DCIS. Recently, iodine-125 seed-guided localization (I-125 GL) was introduced as an alternative localization technique. The aim of this study was to compare the efficacy of these localization techniques in the resection of DCIS by breast-conserving surgery. METHODS: Between March 2006 and June 2013, 169 patients with non-palpable DCIS were treated with breast-conserving surgery. Only patients with pure DCIS on both preoperative core biopsy and definitive pathology were included. RESULTS: WGL was performed in 78 patients and I-125 GL in 91 patients. The groups did not differ with respect to age, size of DCIS or type of imaging used. Patients in the I-125 GL group had a significantly lower risk of extensively involved resection margins than those in the WGL group (4 versus 13 per cent respectively; P = 0·048). CONCLUSION: In patients treated with breast-conserving surgery for non-palpable DCIS, localization with iodine-125 seeds is superior to the WGL technique in reducing the risk of extensively involved resection margins.

Benefits of preoperative MRI in breast cancer surgery studied in a large population-based cancer registry.

BACKGROUND: Although evidence for the benefits of preoperative MRI in breast cancer is lacking, use of MRI is increasing and characterized by large interhospital variation. The aim of the study was to evaluate MRI use and surgical outcomes retrospectively. METHODS: Women with invasive breast cancer (pT1-3) or ductal carcinoma in situ (DCIS), diagnosed in 2011-2013, were selected from the Netherlands Cancer Registry and subdivided into the following groups: invasive cancer, high-grade DCIS, non-palpable cancer, age 40 years or less, and invasive lobular cancer. Associations between preoperative MRI use and initial mastectomy, resection margin after breast-conserving surgery (BCS), re-excision after BCS, and final mastectomy were analysed. RESULTS: In total, 5514 women were included in the study; 1637 (34·1 per cent) of 4801 women with invasive cancer and 150 (21·0 per cent) of 713 with DCIS had preoperative MRI. Positive resection margins were found in 18·1 per cent women who had MRI and in 15·1 per cent of those who did not (adjusted odds ratio (OR) 1·20, 95 per cent c.i. 1·00 to 1·45), with no differences in subgroups. Re-excision rates were 9·8 per cent in the MRI group and 7·2 per cent in the no-MRI group (adjusted OR 1·33, 1·04 to 1·70), with no differences in subgroups. In the MRI group, 38·8 per cent of patients ultimately underwent mastectomy, compared with 24·2 per cent in the no-MRI group (adjusted OR 2·13, 1·87 to 2·41). This difference was not found for patients aged 40 years or less, or for those diagnosed with lobular cancer. CONCLUSION: No subgroup was identified in which preoperative MRI influenced the risk of margin involvement or re-excision rate after BCS. MRI was significantly associated with more extensive surgery, except in patients aged 40 years or less and those with invasive lobular cancer. These results suggest that use of preoperative MRI should be more targeted, and that general, widespread use be discouraged.

Two decades of axillary management in breast cancer.

BACKGROUND: Axillary lymph node dissection (ALND) in patients with breast cancer provides prognostic information. For many years, positive nodes were the most important indication for adjuvant systemic therapy. It was also believed that regional control could not be achieved without axillary clearance in a positive axilla. However, during the past 20 years the treatment and staging of the axilla has undergone many changes. This large population-based study was conducted in the south-east of the Netherlands to evaluate the changing patterns of care regarding the axilla, including the introduction of sentinel lymph node biopsy (SLNB) in the late 1990s, implementation of the results of the American College of Surgeons Oncology Group Z0011 study, and the initial effects of the European Organization for Research and Treatment of Cancer AMAROS study. METHODS: Data from the population-based Eindhoven Cancer Registry of all women diagnosed with invasive breast cancer in the south of the Netherlands between January 1993 and July 2014 were used. RESULTS: The proportion of 34,037 women staged by SLNB without completion ALND increased from 0 per cent in 1993-1994 to 69·0 per cent in 2013-2014. In the same period the proportion undergoing ALND decreased from 88·8 to 18·7 per cent. Among women with one to three positive lymph nodes, the proportion undergoing SLNB alone increased from 10·6 per cent in 2011-2012 to 37·6 per cent in 2013-2014. CONCLUSION: This population-based study demonstrated the radical transformation in management of the axilla since the introduction of SLNB and following the recent publication of trials on management of the axilla with a low metastatic burden.

Concentrated citrate locking in order to reduce the long-term complications of central venous catheters: a randomized controlled trial in patients with hematological malignancies.

PURPOSE AND METHODS: Central venous catheter (CVC)-related thrombosis and infections are frequently occurring complications in patients with hematological malignancies. At present, heparin is most often used as a locking solution. Trisodium citrate (TSC) had been shown to be a very effective antimicrobial catheter locking in hemodialysis patients. We performed a prospective randomized phase III multicenter trial to determine the efficacy of TSC as a locking solution compared to heparin in preventing CVC-related thrombosis and infections in patients with hematological malignancies. RESULTS: Thirty-four episodes of CVC-related bloodstream infections (CVC-BSI) occurred in the 108 patients who were randomized to locking with heparin compared with 35 episodes in the 99 patients who were randomized to locking with TSC (P = 0.654). We did find seven times more CVC-BSI with gram-negative rods in CVCs locked with heparin (P = 0.041). The cumulative incidence of symptomatic thrombosis was 10% in the heparin group and 5% in the TSC group (hazard ratio 0.525; 95% confidence interval 0.182-1.512). CONCLUSION: This study shows that locking with TSC in patients with hematological malignancies significantly reduced the incidence of CVC-BSI with gram-negative rods. However, the incidence of CVC-BSI with coagulase-negative staphylococcus or CVC-related thrombosis was not reduced by TSC locking.

Small but significant excess mortality compared with the general population for long-term survivors of breast cancer in the Netherlands.

BACKGROUND: Coinciding with the relatively good and improving prognosis for patients with stage I-III breast cancer, late recurrences, new primary tumours and late side-effects of treatment may occur. We gained insight into prognosis for long-term breast cancer survivors. PATIENTS AND METHODS: Data on all 205 827 females aged 15-89 diagnosed with stage I-III breast cancer during 1989-2008 were derived from the Netherlands Cancer Registry. Conditional 5-year relative survival was calculated for every subsequent year from diagnosis up to 15 years. RESULTS: For stage I, conditional 5-year relative survival remained ~95% up to 15 years after diagnosis (a stable 5-year excess mortality rate of 5%). For stage II, excess mortality remained 10% for those aged 15-44 or 45-59 and 15% for those aged 60-74. For stage III, excess mortality decreased from 35% at diagnosis to 10% at 15 years for those aged 15-44 or 45-59, and from ~40% to 30% for those aged ≥60. CONCLUSIONS: Patients with stage I or II breast cancer had a (very) good long-term prognosis, albeit exhibiting a small but significant excess mortality at least up to 15 years after diagnosis. Improvements albeit from a lower level were mainly seen for patients who had been diagnosed with stage III disease. Caregivers can use this information to better inform (especially disease-free) cancer survivors about their actual prognosis.

Prognostic factors for survival in metastatic breast cancer by hormone receptor status.

Hormone receptor (HR) status is an important prognostic factor for patients with metastatic breast cancer (MBC) and is also correlated with other prognostic factors, such as initial lymph node status, HER2-Neu status and age. The prognostic value of these other factors, however, is unknown when stratified by HR positive versus HR negative patients. The aim of this study was to evaluate prognostic factors for MBC survival in relation to HR status. Dutch women diagnosed with breast cancer in 2003-2006 treated with curative intent who developed MBC within 5 years of follow-up were selected from the Netherlands cancer registry (N = 2,001). Independent prognostic factors for survival after metastatic occurrence were determined by multivariable Cox survival analyses stratified by HR status. Interactions between HR status and prognostic factors were determined. Median survival for MBC patients with HR negative (HR-) tumours was 8 months, compared to 19 months for HR positive (HR+) patients. The prognostic value of lymph node status, HER2-Neu status, adjuvant endocrine treatment and first-line palliative chemotherapy was dependent on HR status. Initial lymph node status was independently associated with survival in HR- patients, but not in HR+ patients. HER2-Neu positive status was associated with better survival in both HR+ and HR- patients, although the association was stronger in HR- patients. Similarly, patients treated with first-line palliative chemotherapy fared better, especially HR- patients. HR+ patients had worse survival if they had received adjuvant endocrine treatment. This study shows that the prognostic value of various factors depends on HR status in MBC. This information may help physicians to determine individual prognostic profiles and therapeutic strategies for MBC patients.

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.

Trends in surgery for screen-detected and interval breast cancers in a national screening programme.

BACKGROUND: This population-based study aimed to evaluate trends in surgical approach for screen-detected cancer versus interval breast cancer, and to determine the factors associated with positive resection margins. METHODS: Screening mammograms of women aged 50-75 years, who underwent biennial screening in a Dutch breast-screening region between 1997 and 2011, were included. Patient and tumour characteristics were compared between women who underwent mastectomy or breast-conserving surgery (BCS) for screen-detected or interval cancer, and women with a negative or positive resection margin after BCS. RESULTS: Some 417,013 consecutive screening mammograms were included. A total of 2224 screen-detected and 825 interval cancers were diagnosed. The BCS rate remained stable (mean 6.1 per 1000 screened women; P = 0.099), whereas mastectomy rates increased significantly during the study from 0.9 (1997-1998) to 1.9 (2009-2010) per 1000 screened women (P < 0.001). The proportion of positive resection margins for invasive cancer was 19.6 and 7.6 per cent in 1997-1998 and 2009-2010 respectively (P < 0.001), with significant variation between hospitals. Dense breasts, preoperative magnetic resonance imaging, microcalcifications, architectural distortion, tumour size over 20 mm, axillary lymph node metastasis and treating hospital were independent risk factors for mastectomy. Interval cancer, image-guided tumour localization, microcalcifications, breast parenchyma asymmetry, tumour size greater than 20 mm, lobular tumour histology, low tumour grade, extensive invasive component and treating hospital were independent risk factors for positive resection margins. CONCLUSION: Mastectomy rates doubled during a 14-year period of screening mammography and the proportion of positive resection margins decreased, with variation among hospitals. The latter observation stresses the importance of quality control programmes for hospitals treating women with breast cancer.

Variations in screening outcome among pairs of screening radiologists at non-blinded double reading of screening mammograms: a population-based study.

OBJECTIVES: Substantial inter-observer variability in screening mammography interpretation has been reported at single reading. However, screening results of pairs of screening radiologists have not yet been published. We determined variations in screening performances among pairs of screening radiologists at non-blinded double reading. METHODS: We included pairs of screening radiologists with at least 7,500 screening examinations per pair, obtained between 1997 and 2011. During 2-year follow-up, breast imaging reports, surgical reports and pathology results were collected of all referred women and interval cancers. Referral rate, cancer detection rate, positive predictive value and sensitivity were calculated for each pair. RESULTS: A total of 310,906 screening mammograms, read by 26 pairs of screening radiologists, were included for analysis. The referral rate ranged from 1.0 % (95 % CI 0.8 %-1.2 %) to 1.5 % (95 % CI 1.3 %-1.8 %), the cancer detection rate from 4.0 (95 % CI 2.8-5.2) to 6.3 (95 % CI 4.5-8.0) per 1,000 screens. The programme sensitivity and positive predictive value of referral ranged from 55.1 % (95 % CI 45.1 %-65.1 %) to 81.5 % (95 % CI 73.4 %-89.6 %) and from 28.7 % (95 % CI 20.8 %-36.6 %) to 49.5 % (95 % CI 39.7 %-59.3 %), respectively. CONCLUSION: We found significant variations in screening outcomes among pairs of screening radiologists at non-blinded double reading. This stresses the importance of monitoring screening results on a local scale. KEY POINTS: • Substantial inter-observer variability in screening mammography interpretation is known at single reading • Population-based study showed significant variations in outcomes among pairs of screening radiologists • Local monitoring and regular feedback are important to optimise screening outcome.