Treatment and survival of patients diagnosed with high-risk HR+/HER2- breast cancer in the Netherlands: a population-based retrospective cohort study.

BACKGROUND: Several factors may increase the risk of recurrence of patients diagnosed with hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC). We aim to determine the proportion of patients with high-risk HR+/HER2- BC within the total HR+/HER2- BC cohort and compare their systemic treatments and survival rates with those of patients with low- and intermediate-risk HR+/HER2- BC and triple-negative (TN) BC. PATIENTS AND METHODS: Women diagnosed with nonmetastatic invasive HR+/HER2- BC and TNBC in the Netherlands between 2011 and 2019 were identified from the Netherlands Cancer Registry. Patients with HR+/HER2- BC were categorised according to risk profile, defined by nodal status, tumour size, and histological grade. High-risk HR+/HER2- BC was defined by either four or more positive lymph nodes or one to three positive lymph nodes with a tumour size of ≥5 cm or a histological grade 3 tumour. Overall survival (OS) and relative survival (RS) were calculated using the Kaplan-Meier and Pohar-Perme method. RESULTS: In this study of 87 455 patients with HR+/HER2- BC, 44 078 (50%) patients were diagnosed with low risk, 28 452 (33%) with intermediate risk, and 11 285 (13%) with high-risk HR+/HER2- BC. In 3640 (4%) patients, the risk profile could not be defined. Endocrine therapy and chemotherapy were used in 38% and 7% of low-risk, 90% and 47% of intermediate-risk, and 94% and 73% of high-risk patients, respectively. The 10-year OS and RS rates were 84.1% [95% confidence interval (95% CI) 83.5% to 84.7%] and 98.7% (95% CI 97.3% to 99.4%) in low-risk, 75.1% (95% CI 74.2% to 76.0%) and 91.7% (95% CI 89.7% to 93.3%) in intermediate-risk, and 63.4% (95% CI 62.0% to 64.7%) and 72.3% (70.1% to 74.3%) in high-risk patients. The 10-year OS and RS rates of 12 689 patients with TNBC were 69.7% (95% CI 68.6% to 70.8%) and 79.1% (95% CI 77.0% to 80.9%), respectively. CONCLUSION: The poor prognosis of patients with high-risk HR+/HER2- BC highlights the need for a better acknowledgement of this subgroup and supports ongoing clinical trials aimed at optimising systemic therapy.

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Transoral endoscopic thyroidectomy vestibular approach (TOETVA): a novel option in the treatment of pediatric patients. / Tiroidectomía transoral endoscópica con abordaje vestibular (TOETVA): una nueva opción para el tratamiento de pacientes pediátricos.

INTRODUCTION: Thyroid surgery has increased in the pediatric population. One of the main issues following this surgery is the presence of a neck scar, which has been reported to have an impact on quality of life. Transoral endoscopic thyroidectomy is used in adult patients with good results, but there are few reports on the use of this technique in pediatrics. CLINICAL CASE: 17-year-old female patient diagnosed with toxic nodular goiter. As a result of the patient's refusal to undergo conventional surgery due to the scar, transoral endoscopic lobectomy was carried out. The surgical technique used will be described. DISCUSSION: In order to prevent the psychological and social impact of neck scars in children, and given the results published on the use of this technique in pediatrics, transoral endoscopic thyroidectomy stands as an alternative to conventional thyroidectomy in adequately selected patients eager to avoid neck scars.

INTRODUCCION: La cirugía tiroidea ha aumentado en la edad pediátrica, y uno de los problemas luego de esta cirugía es la presencia de una cicatriz cervical, que se reportó como causa de alteración en la calidad de vida. La tiroidectomía transoral endoscópica se utiliza en pacientes adultos con buenos resultados, pero hay escasos reportes de la utilización de esta técnica en pediatría. CASO CLINICO: Paciente femenina de 17 años con diagnóstico de bocio nodular tóxico. Ante la negativa de realizarse una cirugía convencional por la cicatriz, se realizó lobectomía transoral endoscópica. Se detalla la técnica quirúrgica. COMENTARIOS: Con el objetivo de prevenir alteraciones psico-sociales que pueden provocar las cicatrices cervicales en niños, y con los resultados publicados sobre la utilización de esta técnica en pediatría, podemos decir que la tiroidectomía transoral endoscópica puede ser una alternativa a la tiroidectomía convencional en pacientes adecuadamente seleccionados que deseen evitar una cicatriz cervical.

Tiroidectomía transoral endoscópica con abordaje vestibular (TOETVA): una nueva opción para el tratamiento de pacientes pediátricos / Transoral endoscopic thyroidectomy vestibular approach (TOETVA): a novel option in the treatment of pediatric patients

Introducción: La cirugía tiroidea ha aumentado en la edad pediátri-ca, y uno de los problemas luego de esta cirugía es la presencia de unacicatriz cervical, que se reportó como causa de alteración en la calidadde vida. La tiroidectomía transoral endoscópica se utiliza en pacientesadultos con buenos resultados, pero hay escasos reportes de la utilizaciónde esta técnica en pediatría. Caso clínico: Paciente femenina de 17 años con diagnóstico debocio nodular tóxico. Ante la negativa de realizarse una cirugía con-vencional por la cicatriz, se realizó lobectomía transoral endoscópica.Se detalla la técnica quirúrgica. Comentarios: Con el objetivo de prevenir alteraciones psico-so-ciales que pueden provocar las cicatrices cervicales en niños, y con losresultados publicados sobre la utilización de esta técnica en pediatría,podemos decir que la tiroidectomía transoral endoscópica puede ser unaalternativa a la tiroidectomía convencional en pacientes adecuadamenteseleccionados que deseen evitar una cicatriz cervical.(AU)

Introduction: Thyroid surgery has increased in the pediatric population. One of the main issues following this surgery is the presence of aneck scar, which has been reported to have an impact on quality of life. Transoral endoscopic thyroidectomy is used in adult patients with goodresults, but there are few reports on the use of this technique in pediatrics.Clinical case: 17-year-old female patient diagnosed with toxic nodular goiter. As a result of the patient’s refusal to undergo conventionalsurgery due to the scar, transoral endoscopic lobectomy was carried out.The surgical technique used will be described. Discussion: In order to prevent the psychological and social impactof neck scars in children, and given the results published on the use ofthis technique in pediatrics, transoral endoscopic thyroidectomy standsas an alternative to conventional thyroidectomy in adequately selectedpatients eager to avoid neck scars.(AU)

Trends in delayed breast cancer diagnosis after recall at screening mammography.

OBJECTIVES: To determine the extent and characteristics of delay in breast cancer diagnosis in women recalled at screening mammography. METHODS: We included a consecutive series of 817,656 screens of women who received biennial screening mammography in a Dutch breast cancer screening region between 1997 and 2016. During at least 3.5 years follow-up, radiological reports and biopsy reports were collected of all recalled women. The inclusion period was divided into four cohorts of four years each. We determined the number of screen-detected cancers and their characteristics, and assessed the proportion of recalled women who experienced a diagnostic delay of at least 4 months in breast cancer confirmation. RESULTS: The proportion of recalled women who experienced diagnostic delay decreased from 7.5 % in 1997-2001 (47/623) to 3.0 % in 2012-2016 (67/2223, P < 0.001). The proportion of women with a delay of at least two years increased from 27.7 % (13/47) in 1997-2001 to 75.7 % (53/70) in 2012-2016 (P < 0.001). Cancers with a diagnostic delay > 2 years were more frequently invasive (P = 0.009) than cancers with a diagnostic delay of 4-24 months. The most frequent cause of diagnostic delays was incorrect radiological classifications by clinical radiologists (55.2 % overall) after recall. CONCLUSIONS: The proportion of recalled women with a delayed breast cancer diagnosis has more than halved during two decades of screening mammography. Delays in breast cancer diagnosis are characterized by longer delay intervals, although the proportion of these delays among all screen-detected cancers has not increased. Preventing longer delays in breast cancer confirmation may help improve breast cancer survival.

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.

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.

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.

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.

[A plea for selective use of the MammaPrint test]. / Pleidooi voor selectief gebruik van de MammaPrint.

Recently, the results of the MINDACT study were published in The New England Journal of Medicine. The authors conclude that the MammaPrint test can prevent the use of chemotherapy in about 50% of breast cancer patients with a high-risk clinical profile because of the presence of a genomic low risk MammaPrint. We believe that the decision to use chemotherapy should not be based solely on the outcome of the MammaPrint test, as is suggested by the authors, but also on clinical factors, such as tumour size, nodal status and grade. We demonstrate that the use of MammaPrint should be limited to those patients in whom the survival benefit of chemotherapy on the 10-year survival rate is 2-4%, as calculated with New Adjuvant Online, and assuming that patients consider an absolute survival benefit of 3% or more due to chemotherapy worthwhile.

Potential impact of application of Z0011 derived criteria to omit axillary lymph node dissection in node positive breast cancer patients.

BACKGROUND: The ACOSOG Z0011 trial, a randomized controlled trial among patients with sentinel node positive breast cancer treated with breast conserving therapy, concluded that axillary lymph node dissection (ALND) can be omitted in these patients. However, questions were raised on the general applicability if the results of the Z0011 trial. Therefore, the aim of this study was to assess the practice changing effect of the Z0011 trial by quantifying the proportion of all node positive breast cancer patients who meet the inclusion criteria which are based on the Z0011 trial, thus in whom an ALND could be omitted. METHODS: A multicenter population based study including patients with clinical T1-2N0-1M0 invasive non-metastatic breast cancer, a positive sentinel node or ultrasound guided lymph node biopsy, treated with breast conserving therapy and adjuvant systemic therapy between January 2007 and December 2012. RESULTS: A total of 11,031 patients had invasive breast cancer including 3051 cases treated with breast conserving therapy and adjuvant systemic therapy. Subsequently, 916 cases with a positive nodal status underwent an ALND of whom 558 cases (60.9%), representing 5.1% of the total breast cancer population, would potentially have fulfilled the Z0011 criteria. CONCLUSION: Application of Z0011 based criteria is practice changing in nearly 61% of all node positive patients, which could result in omission of the ALND in a substantial number of patients in the future. Further research has to be performed on the applicability of these conclusions to other categories of breast cancer patients.

Management of the axilla after neoadjuvant chemotherapy for clinically node positive breast cancer: A nationwide survey study in The Netherlands.

BACKGROUND: Axillary pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is achieved in a substantial part of clinically node positive breast cancer patients. Treatment of the axilla after NAC varies widely, and new techniques to spare patients from an axillary lymph node dissection (ALND) are being introduced. METHODS: This Dutch nationwide survey regarding treatment of the initially clinically node positive axilla in patients receiving NAC was conducted amongst 148 surgical oncologists during November 2014-June 2015, to survey the diagnostic work-up, axillary mapping and willingness to omit ALND. RESULTS: Axillary ultrasound was considered a standard procedure in the diagnostic work-up by 99% of participants. The majority of 70% of participants stated that ALND could possibly be omitted in node positive patients with a favourable response to NAC. A positive correlation was observed between the total amount of patients treated, versus patients receiving NAC (P < 0.01). A total of 93 respondents performed axillary response evaluation after NAC, using imaging (72%), excision of localized lymph nodes (56%) or sentinel node biopsy (SNB; 45%). Decision-making in omitting ALND was influenced by the presence of N2-3 disease, patient age and type of breast surgery. Multivariable analysis showed that clinicians who administered NAC more often, were more likely to omit ALND (P < 0.01). DISCUSSION: The majority of surgeons are inclined to omit ALND in case of an axillary pCR. A large variety of techniques is being used to identify a pCR. The lack of consensus on this topic indicates the need for guidelines based on the best available evidence.

Predictors for extensive nodal involvement in breast cancer patients with axillary lymph node metastases.

PURPOSE: Various prediction models have been developed to predict the risk of having no additional axillary metastases in patients with a positive sentinel lymph node biopsy (SLNB), thereby disregarding patients with a positive ultrasound-guided lymph node biopsy (UGLNB). However, in the post-Z0011 trial era it is important to identify all patients with extensive nodal involvement for whom axillary treatment might still be beneficial. Therefore, the aim of this study is to identify factors predicting extensive nodal involvement (≥3 positive nodes) in the axilla, with the emphasis on the method of axillary staging: node positivity by UGLNB versus SLNB. METHODS: All patients diagnosed with invasive breast cancer between January 2006 and December 2011 at the Máxima Medical Center were included. Univariate and multivariate logistic regression analyses were performed. RESULTS: We included 302 cases, representing 301 node positive patients, of whom 177 cases had 1 or 2 positive lymph nodes and 125 cases had ≥3 positive lymph nodes. Multivariate analyses showed that a positive UGLNB (OR = 5.10; 95%CI = 2.78-9.36), lymphovascular invasion (OR = 3.60; 95%CI = 1.79-7.23) and a larger tumor size (OR = 1.03 per mm increase; 95%CI = 1.00-1.06) were significantly associated with extensive nodal involvement in patients with invasive breast cancer. CONCLUSION: This study shows that a positive axilla, determined by UGLNB, is the most important factor for predicting further extensive nodal involvement. Hence, the role of axillary staging by ultrasound should be redefined since it might play an important role in selecting patients who may still benefit from axillary treatment.

Clinical impact of breast MRI with regard to axillary reverse mapping in clinically node positive breast cancer patients following neo-adjuvant chemotherapy.

BACKGROUND: Axillary reverse mapping (ARM) is a technique that discerns axillary lymphatic drainage of the arm from the breast. In the current study, we retrospectively evaluated the incidence of metastatic axillary lymph node involvement, including ARM lymph nodes, in clinically node positive breast cancer patients (cN+ patients) in whom neo-adjuvant chemotherapy (NAC) was administered followed by primary ALND using breast MRI. PATIENTS AND METHODS: Data from 98 cN+ breast cancer patients were analysed retrospectively. Patients without residual axillary disease at breast MRI following NAC (RAD-, n = 64) were compared with patients with residual axillary disease (RAD+, n = 34). Presence of suspect axillary lymph nodes on pre-NAC and post-NAC breast MRI was determined by experienced breast radiologists and was correlated to histopathological findings. RESULTS: In the RAD-group residual axillary disease on pathological analysis following NAC was found in 25 patients (39.1%), as compared to 24 patients (70.6%) in the RAD + group (p = 0.003). Metastatic involvement of ARM lymph nodes following NAC was demonstrated in 5 patients (7.8%) in the RAD-group as compared to 10 patients (29.4%) in the RAD + group (p = 0.005). CONCLUSION: Breast MRI following NAC is not suitable to detect residual metastatic disease of the axilla. However, breast MRI post-NAC may be of use to identify cN+ patients with a low risk of ARM lymph node metastases. This may help to select a subgroup of cN+ patients in whom sparing of ARM lymph nodes during axillary lymph node dissection can be considered.

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.

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.

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.