Primer consenso español sobre el uso de la radioterapia intraoperatoria en el cáncer de mama. Conclusiones del panel de expertos / First Spanish consensus on the use of intraoperative radiotherapy in breast cancer. Conclusions of the expert panel

Introducción: la publicación de ensayos aleatorizados con resultados a largo plazo ha demostrado que la radioterapia intraoperatoria (RIO) en cáncer de mama en estadio precoz puede ser una alternativa terapéutica en casos bien seleccionados. En el presente trabajo se presentan los resultados del Primer Consenso de Radioterapia Intraoperatoria en Cáncer de Mama realizado de manera multidisciplinar en España. Material y método: se hizo una revisión sistemática de la literatura y se invitó a todos los oncólogos radioterápicos y cirujanos expertos en RIO en cáncer de mama de España a participar en el consenso. Se aplico la siguiente metodología en 2 fases: a) la creación de un grupo de trabajo y la revisión de la evidencia; b) la realización de la encuesta y generación de recomendaciones consensuadas. Resultados: han participado un total 95,65% de los centros que actualmente utilizan esta técnica en cáncer de mama y que fueron invitados. Los expertos estuvieron de acuerdo en el uso de RIO exclusiva en cáncer de mama en aquellas pacientes mayores de 60 años y por encima de 50 años posmenopáusicas, con carcinoma ductal infiltrante o subtipos histológicos favorables, sin invasión linfovascular, tumores menores o iguales a 25 mm, márgenes de resección libres y receptores hormonales positivos. La utilización de RIO como rescate de recidiva local después de la irradiación externa alcanzó un nivel de consenso muy fuerte. Conclusión: el presente consenso pretende establecer las guías respecto a las indicaciones de RIO exclusiva o como sobreimpresión anticipada y ser una ayuda para la toma conjunta de decisiones. (AU)

Introduction: The publication of randomized trials with long-term results has demonstrated that intraoperative radiation therapy (IORT) in early-stage breast cancer can be a therapeutic alternative for well-selected cases. This paper present work presents the results of the first multidisciplinary consensus on IORT in breast cancer carried out in Spain. Materials and methods: A systematic literature review was conducted, and all radiation oncologists and surgeons with expertise in IORT for breast cancer in Spain were invited to participate in the consensus. The following methodology was employed in two phases: a) creation of a working group and review of the evidence; b) conduct of the survey and generation of consensus recommendations. Results: A total of 95.65% of the invited centers currently utilizing this technique in breast cancer participated. The experts agreed on the use of exclusive intraoperative radiation therapy in breast cancer for patients above 60 years of age and above 50 years postmenopausal, with invasive ductal carcinoma or favorable histological subtypes, no lymphovascular invasion, tumors less than or equal to 25 mm, clear surgical margins, and positive hormone receptor. The use of IORT as salvage surgery for local recurrence after external irradiation achieved a very strong consensus level. Conclusion: The present consensus aims to establish guidelines regarding the indications for exclusive IORT or as an early boost, and to serve as an aid for joint decision-making. (AU)

Associations between Menopausal Hormone Therapy and Colorectal, Lung, or Melanoma Cancer Recurrence and Mortality: A Narrative Review.

Objective: to develop eligibility criteria for use in non-gynecological cancer patients. Methods: We searched all the articles published in peer-reviewed journals up to March 2021. We utilized the PICOS standards and the following selection criteria: menopausal women with a history of non-gynecological and non-breast cancer who underwent hormone replacement therapy (HRT) using various preparations (oestrogens alone or in combination with a progestogen, tibolone, or tissue selective oestrogen complex) and different routes of administration (including oral, transdermal, vaginal, or intra-nasal). We focused on randomized controlled trials as well as relevant extension studies or follow-up reports, specifically examining recurrence and mortality outcomes. Results: Women colorectal cancer survivors who use MHT have a lower risk of death from any cause than those survivors who do not use MHT. Women who are skin melanoma survivors using MHT have a longer survival rate than non-MHT survivors. There is no evidence that women lung cancer survivors who use MHT have a different survival rate than those who do not use MHT. Conclusions: MHT is safe for women who have a history of colorectal, lung, or skin melanoma cancers.

Eligibility criteria for Menopausal Hormone Therapy (MHT): a position statement from a consortium of scientific societies for the use of MHT in women with medical conditions. MHT Eligibility Criteria Group.

This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best available evidence. The project was developed in two phases. As a first step, we conducted 14 systematic reviews and 32 metanalyses on the safety of MHT (in nine areas: age, time of menopause onset, treatment duration, women with thrombotic risk, women with a personal history of cardiovascular disease, women with metabolic syndrome, women with gastrointestinal diseases, survivors of breast cancer or of other cancers, and women who smoke) and on the most relevant pharmacological interactions with MHT. These systematic reviews and metanalyses helped inform a structured process in which a panel of experts defined the eligibility criteria according to a specific framework, which facilitated the discussion and development process. To unify the proposal, the following eligibility criteria have been defined in accordance with the WHO international nomenclature for the different alternatives for MHT (category 1, no restriction on the use of MHT; category 2, the benefits outweigh the risks; category 3, the risks generally outweigh the benefits; category 4, MHT should not be used). Quality was classified as high, moderate, low or very low, based on several factors (including risk of bias, inaccuracy, inconsistency, lack of directionality and publication bias). When no direct evidence was identified, but plausibility, clinical experience or indirect evidence were available, "Expert opinion" was categorized. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, has been defined. This will provide health professionals with a powerful decision-making tool that can be used to manage menopausal symptoms.

Effectiveness and safety of intraoperative radiotherapy (IORT) with low-energy X-rays (INTRABEAM®) for accelerated partial breast irradiation (APBI).

PURPOSE: To evaluate treatment outcomes in patients with early-stage breast cancer (ESBC) treated with targeted intraoperative radiation therapy (IORT) administered as accelerated partial breast irradiation (APBI). METHODS: Between December 2014 and May 2019, 50 patients diagnosed with ESBC were treated with a 50 kilovoltage (kV) X-ray source with a single dose of 20 Gy using the Intrabeam® radiotherapy delivery system. All patients were followed prospectively to assess local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), radiation-induced toxicity, and cosmetic outcomes. We also evaluated the prognostic implications of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). RESULTS: Median follow-up was 53 months. Mean patient age was 70 years. The mean duration of radiation delivery was 22.25 min. Two patients developed a recurrence. One death was recorded. Elevated pretreatment NLR levels were a significant risk factor for mortality (p = 0.0026). The most common treatment-related toxicities were breast induration (30%) and seroma (18%). Five-year LC, DFS, CSS, and OS rates were 97.1%, 93.9%, 100%, and 94.4%, respectively. Cosmesis was excellent or good in most cases (94%). CONCLUSION: These findings confirm the effectiveness of a single dose of 20 Gy of IORT with the Intrabeam device as APBI. The toxicity profile was good with excellent cosmesis. These results provide further support for the clinical use of APBI in well-selected patients.

Mastitis granulomatosa asociada a eritema nudoso: estudio de 42 casos / Granulomatous mastitis associated with erythema nodosum: A case series of 42 patients

Introducción:La mastitis granulomatosa (MG) se define por la presencia de inflamación granulomatosa en el tejido mamario. El eritema nudoso (EN) es una paniculitis inflamatoria reactiva caracterizada por nódulos subcutáneos dolorosos en las extremidades inferiores. La asociación entre MG y EN ha sido descrita, pero está poco estudiada. Nuestro objetivo fue analizar las características clínicas de las pacientes diagnosticadas de MG en nuestro centro y su asociación con EN.Métodos:Se revisaron retrospectivamente los casos diagnosticados histológicamente de MG entre 1995 y 2020.Resultados:Cuarenta y dos mujeres fueron diagnosticadas de MG. La edad media al diagnóstico fue de 41,619años y el 59,5% tenían ascendencia sudamericana. El EN se asoció con MG en el 11,9% de las pacientes. Las pacientes con EN fueron diagnosticadas precozmente respecto a aquellas con MG aislada (0,4meses frente a 6,81; p<0,05). La ulceración en la MG fue más prevalente en pacientes con EN asociado (60% vs 14,7%; p<0,05).Conclusión:El EN en pacientes con GM puede facilitar el diagnóstico precoz de esta rara condición que imita el cáncer de mama.(AU)

Background:Granulomatous mastitis (GM) is defined by the formation of granulomatous inflammation in breast tissue. Erythema nodosum (EN) is a reactive inflammatory panniculitis characterized by erythematous subcutaneous nodules in the lower limbs. The association of GM with EN has been rarely reported. Our aim was to retrospectively review our series of patients with GM to better characterize their features and their association with EN.Methods:Cases histologically diagnosed as granulomatous inflammation in breast tissue between 1995 and 2020 were retrospectively reviewed.Results:Forty-two women were diagnosed with GM. The average age at diagnosis was 41.619years, and 59.5% were of South-American ethnicity. EN was associated with GM in 11.9% of the patients. Patients with EN were diagnosed earlier than isolated GM (0.4months vs 6.81months; P<.05). Ulceration in the GM was more prevalent in patients with associated EN (60% vs 14.7%; P<.05).Conclusion:EN in patients with GM may reduce the evolution time and may help to diagnose this rare condition that mimics breast carcinoma. (AU)

[Granulomatous mastitis associated with erythema nodosum: A case series of 42 patients]. / Mastitis granulomatosa asociada a eritema nudoso: estudio de 42 casos.

BACKGROUND: Granulomatous mastitis (GM) is defined by the formation of granulomatous inflammation in breast tissue. Erythema nodosum (EN) is a reactive inflammatory panniculitis characterized by erythematous subcutaneous nodules in the lower limbs. The association of GM with EN has been rarely reported. Our aim was to retrospectively review our series of patients with GM to better characterize their features and their association with EN. METHODS: Cases histologically diagnosed as granulomatous inflammation in breast tissue between 1995 and 2020 were retrospectively reviewed. RESULTS: Forty-two women were diagnosed with GM. The average age at diagnosis was 41.619years, and 59.5% were of South-American ethnicity. EN was associated with GM in 11.9% of the patients. Patients with EN were diagnosed earlier than isolated GM (0.4months vs 6.81months; P<.05). Ulceration in the GM was more prevalent in patients with associated EN (60% vs 14.7%; P<.05). CONCLUSION: EN in patients with GM may reduce the evolution time and may help to diagnose this rare condition that mimics breast carcinoma.

Prophylactic incisional negative pressure wound therapy for gynaecologic malignancies.

Wound complications are an important cause of postoperative morbidity among patients with gynaecologic malignancies. We evaluated whether the placement of closed-incisional negative pressure therapy (ciNPT) at the time of laparotomy for gynaecologic cancer surgery reduced wound complication rates. A retrospective cohort study with primary wound closure performed by a gynaecologic oncologist was carried out. We evaluated two cohorts of patients who underwent surgery in 2017 with standard closure and patients who underwent surgery in 2019 with the placement of prophylactic ciNPT. Postoperative outcomes were examined. A total of 143 patients were included, 85 (59.4%) vs 58 (40.6%) with standard closure and ciNPT, respectively. The total complication rate in our sample was 38.71%. The rate of surgical complications in patients treated with ciNPT was 6.9% compared with 31.8% (P = .000) in patients treated with standard closure. In the analysis of complications, a significant reduction in infections (17.1%), seromas (15.4%), and wound dehiscence (17.1%) were observed when ciNPT was applied. The median hospital stay was 8 vs 6 days in the standard closure vs ciNPT groups (P = .048). The use of the prophylactic ciNPT following a laparotomy may decrease wound complications and hospital stays in oncological patients. ciNPT could be considered as part of clinical practice in patients at high risk of wound complications, such as patients with gynaecological malignancies.

Genetic platforms: Do we do what we know? or do we know what we do? / Plataformas genéticas: ¿hacemos lo que sabemos? o ¿sabemos lo que hacemos?

Molecular and genomic pathology is an essential cornerstone of diagnosis in breast disease, to such an extent that genetic information is already included in therapeutic decision-making. There are now various commercial platforms available in the clinic, generally with little or no agreement in the genes included, in their technical basis, in the definition of risk groups, in the information they provide, in their indications or in the protocols required to use them. Objective To evaluate the use and knowledge of these platforms. Material and methods An eleven-question survey was conducted targeting breast units accredited by the SESPM in Spain at that time. Results 26 units out of the 36 surveyed responded and data was obtained that can guide the use of the platforms and serve as a starting point towards gaining a deeper knowledge of them. Conclusions The indications approved by the Autonomous Regions need to be re-evaluated. There is insufficient evidence to base decisions about the axilla on the platforms. MammaPrint® is the only platform with level of evidence 1a for N1–3 patients. It also identifies a subgroup of patients who may not require hormonal treatment. (AU)

La enfermedad molecular y genómica constituye un pilar irrenunciable del diagnóstico en enfermedad mamaria, de tal manera que la información genética ha sido ya integrada en la toma de decisiones terapéuticas. Actualmente, existen diferentes plataformas comerciales disponibles en la clínica, generalmente con pocas o nulas coincidencias en los genes incluidos, en su fundamento técnico, en la definición de grupos de riesgo, en la información que proporcionan, en sus indicaciones y en el circuito requerido para la realización de las mismas. Objetivo Evaluar el uso y conocimiento de dichas plataformas. Material y métodos Se realizó una encuesta de 11 preguntas dirigidas a las unidades de mama acreditadas en España por la SESPM en ese momento. Resultados Respondieron 26 unidades de 36 encuestadas y se obtuvieron datos que pueden ser orientativos acerca del uso de las plataformas y pueden servir como punto de partida para profundizar en su conocimiento. Conclusiones Es necesario re-evaluar indicaciones aprobadas por las CC.AA. No existe evidencia suficiente para tomar decisiones sobre la axila en función de la plataforma. MammaPrint® es la única plataforma con evidencia IA para pacientes N1-3. Además, identifica un subgrupo de pacientes que pueden no requerir tratamiento hormonal. (AU)

Five-year results of accelerated partial breast irradiation: A single-institution retrospective review of 289 cases.

PURPOSE: The purpose of the study was to describe our institutional experience with accelerated partial breast irradiation (APBI) using multicatheter brachytherapy with high-dose-rate. We report 5-year survival outcomes, cosmesis, and treatment-related toxicity. METHODS AND MATERIALS: This included a retrospective review of patients who underwent breast-conserving surgery followed by APBI at our institution from 2004 to 2017. RESULTS: A total of 289 patients were evaluated. Median followup was 72 months. Median age was 70 years. APBI was the only primary treatment in 86.2% of cases with early-stage breast cancer and a second conservative treatment in 13.8%. The implant was performed postoperatively in 213 patients (73.7%) and intraoperatively in 76 (26.3%). The most common radiation schemes were 10 fractions of 3.4 Gy and eight fractions of 4 Gy. Elderly or frail patients (10%) received a single 16 Gy dose. Of the 289 patients, 215 met Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology criteria for APBI; in this group, late side effects included Grade 2 (G2) fibrosis (14.8%), skin discoloration at the catheter points (8.8%), and telangiectasia (0.5%). The cosmetic result was considered excellent or good in 88.3% of cases. Five-year local control, disease-free, cancer-specific, and overall survival rates were 98.9%, 96.7%, 99.1%, and 95.6%, respectively. CONCLUSIONS: Local control and survival outcomes at 5 years of followup in this group of well-selected patients were excellent, with low rates of treatment-related toxicity. These findings confirm the safety and effectiveness of APBI, even in elderly and frail patients. These results provide further support for the clinical use of APBI in suitable patients.

Digital quantification of KI-67 in breast cancer.

Ki-67 proliferative index (Ki-67) is a predictive and prognostic factor in breast cancer (BC). However, some international committees do not recommend its use in routine practice due to insufficient clinical evidence and lack of standardisation and assessment method reproducibility. Scoring of Ki-67 by digital pathology may contribute to overcome these drawbacks. We evaluated 136 core biopsies of BC patients and calculated the correlation of Ki-67 scored by two breast pathologists with two methods, eyeballing visual assessment (EB) on the microscope and digital image analysis (DI), both assessed from hot spot areas (HS) and the average between hot and cold spot areas (AVE). Good and higher correlation between pathologists was observed for HS using DI in comparison to EB (0.861 vs. 0.828). Correlation in HS with both methods was very similar in homogeneous tumours (0.869 vs. 0.866). Lower correlation was found in heterogeneous tumours if EB was used instead of DI (0.691 vs. 0.838). Good agreement with DI in AVE areas was observed in both homogenous and heterogeneous tumours (0.898 and 0.887). Concordance of tumour molecular profiles based on Ki-67 was better using DI in comparison to EB (Kappa index, 0.589 vs. 0675). Whereas EB and DI were alike in homogeneous tumour, DI improved agreement in heterogeneous tumours, particularly in AVE areas. Subgroup analysis for tumour grades also showed improvement of correlation by DI in AVE areas in all G1/G2/G3 groups. Digital pathology using AVE method can be useful for Ki-67 scoring in daily practice, especially in heterogeneous and G2 tumours, by a substantial improvement of agreement between observers and results accuracy.

Correction: Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness.

[This corrects the article DOI: 10.1371/journal.pone.0132546.].

The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer Patients. Results, and the Advantages and Disadvantages of Both Procedures.

BACKGROUND: In patients with breast cancer who are candidates for neoadjuvant therapy (NAT), the timing of when to perform sentinel lymph node biopsy (SLNB) remains under discussion. The aim of this study was to compare the advantages and disadvantages of SLNB performed before and after NAT. PATIENTS AND METHODS: One hundred seventy-two patients, T1c to T3 and N0 (clinically and according to ultrasound) candidates for NAT were included. We compared the outcomes of 2 groups: (1) 122 patients of whom SLNB was performed before NAT (pre-NAT) from December 2006 to April 2014; and (2) 50 patients with SLNB performed after NAT (post-NAT) from May 2014 to July 2016. RESULTS: Both groups were homogeneous in baseline patient characteristics. The SLNB was positive in 50 patients [41.7%] (33 macrometastases [66%] and 17 micrometastases [34%]) versus 6 patients [12%] (5 macrometastases [83.3%] and 1 micrometastases [16.7%]) in pre- and post-NAT groups, respectively. The lymphadenectomy was performed in 34 patients [28.3%] versus 4 patients [8%], with an odds ratio of 3.48 (95% confidence interval, 1.3-9.3). The recurrences in the pre-NAT group after a median follow-up of 62 months were 12 systemic, 2 local and systemic, and none axillary. In the post-NAT group were no recurrences after a median follow-up of 16 months. Finally, SLNB after NAT reduces the delay in starting NAT from 24 to 14 days (medians; P < .001) and the identification of the SLNB was in 122 patients [100%] versus 49 patients [98%]. CONCLUSION: SLNB performed after NAT significantly reduces the rate of lymphadenectomies without any increase in recurrences at early follow-up. Furthermore, it allows systemic treatment to be started earlier without interfering in the SLNB identification rate.

Estudio comparativo entre el método One step nucleic acid amplification y el método convencional en la estadificación en cáncer de mama: un aumento en la detección de micrometástasis / Comparative study of the One step nucleic acid amplification method and the conventional method in axillary staging in breast cancer: an increase in the detection of micrometastases

Objetivos. El método One step nucleic acid amplification (OSNA) se ha incorporado para el estudio del ganglio centinela (GC) en cáncer de mama como alternativa al estudio convencional histológico (MC). El propósito de nuestro estudio fue comparar la estadificación por ganglio centinela (EGC) obtenida por el método OSNA con la obtenida mediante MC. Material y métodos. Se seleccionaron pacientes con cáncer de mama y EGC recogidas durante los años 2009-2010 y 2012-2013, estudiadas con MC y método OSNA. Se analizaron diferentes parámetros clínico-patológicos. Resultados. Se incluyó a 1.124 pacientes, 590 estudiadas por MC y 534 por método OSNA. La EGC inicial fue: pN0: MC 349 (59,2%) y OSNA 335 (62,7%); pN0(i+): MC 74 (12,5%) y OSNA 14 (2,6%); pN1mi: MC 59 (10%) y OSNA 77 (14,4%); pN1: MC 108 (18,3%) y OSNA 108 (20,3%). Se encontraron diferencias estadísticamente significativas entre la EGC por método OSNA y MC (p<0,001), a expensas de las tasas de pN1mi y pN0(i+). Se seleccionó a 224 pacientes con EGC pN1mi y pN0(i+) para determinar si las diferencias encontradas podrían atribuirse a distintas características clínico-patológicas. El método OSNA detecta el doble de micrometástasis (84,6%). Conclusiones. En nuestra casuística, por el método OSNA se observa un incremento significativo de pN1mi (84,6% vs. 44,4%) y una disminución de pN0(i+) respecto al estudio convencional, diferencias que no están condicionadas por los parámetros clínico-patológicos. El 75% de casos con pN1mi por OSNA muestra un número de copias inferior a 1.000 (AU)

Objetives. The One Step Nucleic Acid Amplification (OSNA) method has been incorporated in the study of the sentinel lymph node (SLN) in breast cancer as an alternative to conventional histological study. The aim of our study was to compare sentinel lymph node staging (SLNS) obtained by the OSNA method with that obtained by the conventional method (CM). Material and methods. We identified patients with breast cancer and SLN study during the periods 2009-2010 and 2012-2013, who underwent the CM and by OSNA. We analysed different clinicopathological parameters. Results. A total of 1124 patients were studied, 590 by CM and 534 by OSNA. SLNS was: pN0: CM 349 (59.2%) and OSNA 335 (62.7%); pN0(i+): CM 74 (12.5%) and OSNA 14 (2.6%); pN1mi: CM 59 (10%) and OSNA 77 (14.4%); pN1: CM 108 (18.3%) and OSNA 108 (20.3%). Statistically significant differences were found between the SLNS by OSNA and CM (p <0.001), due to the rates of pN1mi and pN0(i+). To determine whether this statistical significance could be attributed to different clinicopathological features, 224 patients were selected from the initial series with SLN pN1mi and pN0(i+). In this subgroup, the OSNA method detected twice as many micrometastases (pN1mi) (84.6%). Conclusions. In our series, the OSNA method resulted in a significant increase in pN1mi (84.6% vs 44.4%) and a decrease in pN0(i+) compared with the conventional method. Those differences were not affected by clinicopathological parameters. Most cases (75%) with pN1mi by OSNA showed less than 1000 copies (AU)

Study of breast cancer incidence in patients of lymphangioleiomyomatosis.

Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM.

Robotic Transperitoneal Infrarenal Para-Aortic Lymphadenectomy With Double Docking: Technique, Learning Curve, and Perioperative Outcomes.

Para-aortic lymphadenectomy (PAL) is a challenging procedure performed by minimally invasive surgery in very few centers, owing to its intrinsic technical complexity. We describe and assess the feasibility and learning curve of robotic double-docking transperitoneal infrarenal PAL combined with oncological pelvic surgery. Fifty patients who underwent this procedure using the Da Vinci S surgical system between March 2010 and May 2013 were included. The mean operating time for PAL surgery was 76 minutes (range, 32-150 minutes), and the mean number of lymph nodes per patient was 11.8 (range, 1-44). There were no conversions to laparotomy or laparoscopy. The mean length of hospital stay was 2 days (range, 1-25 days). Statistically significant decreases were noted for mean table rotation time (17 ± 6.8 minutes vs 13 ± 3.6 minutes; p = .02) and mean PAL operating time (85.4 ± 25.8 minutes vs 69.8 ± 24.6 minutes; p = .04) when comparing the first 20 patients and the last 30 patients. The number of nodes was similar in the first 20 patients and last 30 patients. The double-docking transperitoneal infrarenal PAL technique combined with oncological pelvic surgery is feasible, with minimal morbidity and a short learning curve.

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness.

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.

La enfermedad de Paget mamaria en la actualidad. Impacto del tipo de tratamiento quirúrgico sobre la supervivencia / Mammary Paget disease today. Impact of the type of surgical treatment on survival

Objetivos: Analizar el impacto en la evolución y la supervivencia de pacientes con enfermedad de Paget mamaria con tratamiento conservador versus mastectomía. Material y métodos: Estudio retrospectivo de 31 pacientes con enfermedad de Paget mamaria, durante el periodo 2005-2012, en el Institut Català d’Oncologia del Hospital Universitario de Bellvitge. Se incluyó a pacientes operadas con diagnóstico anatomopatológico de enfermedad de Paget mamaria. Se excluyeron casos con diseminación sistémica al diagnóstico. Se analizaron: características radiológicas e histológicas del tumor, estadio, afectación axilar y tipo de cirugía realizada sobre la evolución de la enfermedad (recidiva locorregional o metástasis), mediante test exacto de Fisher. La supervivencia global y libre de enfermedad según tipo de cirugía y tipo histológico se valoró con el test de Kaplan Meyer y el log rank de Mantel-Haenszel. Resultados: Se realizó cirugía conservadora en 14 (45,1%) pacientes y mastectomía en 17 (54,8%). Se detectaron 7 (22,6%) pacientes con metástasis o recidiva locorregional, tras seguimiento medio de 29 meses (20,6 DE). La media de supervivencia global y libre de enfermedad del tratamiento conservador fue de 36 (19,9 DE) y 31 meses (19,2 DE) respectivamente, que no fue inferior a la del grupo de mastectomía de 23 (19,5 DE) y 20 meses (18,9 DE). La invasión de la dermis apareció en el 100% de las pacientes que recidivaron y no se evidenció ningún caso de recaída cuando estuvo ausente. Conclusiones: El tratamiento quirúrgico conservador de pacientes con enfermedad de Paget mamaria no empeora la supervivencia libre de enfermedad ni la global. La invasión dérmica puede ser un factor pronóstico a tener en cuenta en futuros estudios (AU)

Objectives: To analyze the impact of conservative surgery versus mastectomy on recurrence and survival in mammary Paget disease. Material and methods: A retrospective study of 31 patients with a diagnosis of breast cancer from 2005 to 2012 was conducted at the Institut Català d’Oncologia-Hospital Universitario Bellvitge. We included patients with a histological diagnosis of mammary Paget disease who underwent surgery, and excluded patients with metastatic disease at diagnosis. The impact of radiologic and histologic features of the tumor, stage, axillary involvement and type of surgery on disease course (local and/or systemic recurrences) was evaluated by Fisher's exact test. Overall survival and disease-free survival depending on the type of surgery and histology were analyzed by the Kaplan Meier and log rank Mantel-Haenzel tests. Results: Conservative surgery was performed in 14 (45.1%) patients and mastectomy in 17 (54.8%). Seven (22.6%) patients developed metastases and/or recurrence of the primary tumor after a mean follow-up of 29 months (SD 20.6). The mean overall survival and disease-free survival with conservative treatment was 36 months (SD 19.9) and 31 months (SD 19.2), respectively, which was not inferior to that in the mastectomy group, with 23 months (SD 19.5) and 20 months (SD 18.9). Dermal invasion was present in 100% of patients with recurrent disease and in none of those without recurrence. Conclusions: Conservative treatment in mammary Paget disease does not worsen overall and free-disease survival. Future studies should analyze dermal invasion as a prognostic factor (AU)

Efficacy and safety of concurrent trastuzumab plus weekly paclitaxel-FEC as primary therapy for HER2-positive breast cancer in everyday clinical practice.

One of the most efficacious primary therapies in HER2-positive breast cancer was published by the M.D. Anderson group in 2005. This randomized trial evaluated the addition of trastuzumab to a taxane-anthracycline based chemotherapy. Despite largely significant differences in pathological complete response (pCR) in the trastuzumab group (65 vs. 26 %) this regimen did not become a common standard due to toxicity concerns and its premature closure with a small sample size. In order to evaluate the efficacy and safety of this regimen in an off-trial setting we conducted a prospectively monitorized series of consecutive patients with early or locally advanced Her-2 positive breast cancer following the same treatment strategy. Stage II-IIIC HER2-positive breast cancer patients, including inflammatory disease, were treated with weekly-trastuzumab for 24 weeks administered concurrently with all primary chemotherapy containing paclitaxel (80 mg/m(2)) for 12 weeks and 4 cycles of FEC-75 (fluorouracil 500 mg/m(2), epirubicine 75 mg/m(2), and cyclophosphamide 500 mg/m(2)) followed by surgery. The objectives were efficacy, in terms of pCR in both the breast and lymph nodes, and safety, with close cardiac monitoring during and after treatment. From August 2004 to February 2009, 83 patients were included. Most patients (73.5 %) had node involvement and 13.2 % had inflammatory disease. Fifty-one patients (61.4 %) achieved a pCR in breast and axilla (95 % CI 50-72 %). HR-negative tumors were associated with higher pCR rate than HR-positive tumors (77 vs. 48 %, P = 0.006). At a median follow-up of 50.2 months no patient developed symptomatic cardiac failure, and 9 patients (10.8 %) presented a transient asymptomatic decrease in left ventricular ejection fraction. Primary therapy with concurrent trastuzumab plus paclitaxel-FEC for HER2-positive breast cancer in everyday practice is highly effective and safe confirming the results observed in a randomized trial stopped prematurely.

Avoiding axillary treatment in sentinel lymph node micrometastases of breast cancer: a prospective analysis of axillary or distant recurrence.

BACKGROUND: The need for axillary lymph node dissection (ALND) in breast cancer patients with sentinel lymph node (SLN) micrometastases remains controversial. The aims of the study were to evaluate the locoregional failure and outcome of breast cancer patients with sentinel node micrometastases who did not undergo completion ALND. METHODS: Between November 2000 and December 2006, SLN biopsy was successfully performed in 1178 patients with invasive breast carcinoma. Only patients with macrometastasis (>2 mm) underwent ALND, while patients with negative SLN or micrometastases did not undergo further treatment of the axilla, by either surgery or radiotherapy. Regarding adjuvant therapy decision, patients with SLN-micrometastases (pN1(mi)) were considered as node-positive patients. RESULTS: Of 1,178 patients, 59 (5%) had micrometastases. Of those with micrometastases, 14 (24%) underwent ALND because the intraoperative study of the SLN yielded a positive result. With a median follow-up of 60 (range, 8-94) months, none of the patients with SLN micrometastases in whom ALND was omitted developed an axillary recurrence, while one patient in whom ALND was performed developed infraclavicular lymph node recurrence. One patient, who declined postoperative breast irradiation, developed breast recurrence and distant metastasis. CONCLUSIONS: Breast cancer patients with SLN micrometastases in whom ALND was omitted had a very low locoregional failure rate. This study supports the theory that ALND might be avoided in these patients, providing that adjuvant systemic treatment equal to treatment provided to treat node-positive disease is administered. However, longer follow-up and results of additional prospective studies are needed.

Patients with breast cancer and negative sentinel lymph node biopsy without additional axillary lymph node dissection: a follow-up study of up to 5 years.

OBJECTIVE: To analyze the rate of axillary recurrences and survival in patients operated on for breast cancer who had not undergone an axillary lymph node dissection (ALND) because of a negative sentinel node biopsy. METHODS: The study includes 97 patients operated on for breast cancer and selective node biopsy from June 2000 to December 2001 who had a negative sentinel node biopsy and did not undergo ALND. Mean age was 58.2 years (55.9-60.5). Follow-up was done up to 5 years. After surgery all patients underwent clinical examination. Complementary treatment depended on the hospital protocol. Rate of axillary recurrences, presence of distant metastases and survival (Kaplan-Meier method) were studied. RESULTS: After a median follow-up of 4.1 years (2.18-5.25), only 2/95 patients (2.1%) developed distant metastases. Four patients died but only the death of the patient who presented multiple metastases was related to the primary breast cancer (1%). The 5-year overall survival rate was 96%. CONCLUSIONS: (1) Only 1/95 patients studied developed nodal extra-axillary recurrence together with distant metastases. (2) The results obtained support the selective sentinel node biopsy as an accurate technique in the axillary stratification of patients with breast cancer, offering in the cases of negative sentinel node biopsy a safe axillary control after a 5-year follow-up.