Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study.

BACKGROUND: Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer. METHODS: PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II-III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients were randomly assigned (1:1) in permuted blocks of random size (4 or 6), stratified by anatomic stage, previous chemotherapy, age, and geographical region, by use of central telephone-based and web-based interactive response technology, to receive either 2 years of palbociclib (125 mg orally once daily on days 1-21 of a 28-day cycle) with ongoing standard provider or patient-choice adjuvant endocrine therapy (tamoxifen or aromatase inhibitor, with or without concurrent luteinising hormone-releasing hormone agonist), or endocrine therapy alone, without masking. The primary endpoint of the study was invasive disease-free survival in the intention-to-treat population. Safety was assessed in all randomly assigned patients who started palbociclib or endocrine therapy. This report presents results from the second pre-planned interim analysis triggered on Jan 9, 2020, when 67% of the total number of expected invasive disease-free survival events had been observed. The trial is registered with ClinicalTrials.gov (NCT02513394) and EudraCT (2014-005181-30). FINDINGS: Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877). At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9-29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone had invasive disease-free survival events. 3-year invasive disease-free survival was 88·2% (95% CI 85·2-90·6) for palbociclib plus endocrine therapy and 88·5% (85·8-90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76-1·15]; log-rank p=0·51). As the test statistic comparing invasive disease-free survival between groups crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. The most common grade 3-4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths. INTERPRETATION: At the planned second interim analysis, addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing. FUNDING: Pfizer.

Combining Wire Localization of Clipped Nodes with Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer: Preliminary Results from a Prospective Study.

BACKGROUND: The ideal technique for lymph node staging for patients with pathologically confirmed node-positive breast cancer at diagnosis and neoadjuvant chemotherapy (NAC) is unclear. OBJECTIVE: The aim of this study was to analyze the feasibility of wire/clip localization and sentinel lymph node biopsy (SLNB) for the axillary staging of these patients. METHODS: We conducted a prospective study in which lymph node staging was performed using wire localization of positive lymph nodes and an SLNB with dual tracer. All patients who presented no metastatic involvement of the sentinel lymph node (SLN) or clip/wire-marked lymph node were spared an axillary lymph node dissection (ALND). The multidisciplinary committee agreed on axillary treatment for patients with lymph node involvement. RESULTS: Forty-two patients met the inclusion criteria. We identified and extirpated the clip/wire-marked node in all patients (100%), with SLNB performed successfully in 95.3% of patients. The SLN and wire-marked node matched in 80% of patients; 73.8% of patients did not undergo ALND. DISCUSSION AND CONCLUSIONS: Several studies have evaluated the efficacy of various procedures for lymph node marking for women with prechemotherapy lymph node involvement. Most of the studies reported high identification rates (> 94.8%), with false negative rates of < 7%. Similarly, our study allows us to conclude that combined axillary marking (clip and SLNB) in patients with metastatic lymph node at diagnosis and NAC offers a high identification rate (100%) and a high correlation between the wire-marked lymph node and the SLN (80%). This procedure has enabled the suppression of ALND for a significant number of patients (73%).

SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer (2022).

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody-drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM.

Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).

INTRODUCTION: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain. MATERIAL AND METHODS: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients. RESULTS: A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment. CONCLUSION: The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.

[Proposal for a new multidisciplinary therapeutic strategy in the breast cancer patient with sentinel lymph node metastasis]. / Propuesta de una nueva estrategia terapéutica multidisciplinar en la mujer con cáncer de mama y afectación del ganglio centinela.

Sentinel lymph node (SLN) biopsy is the standard of practice for assessing axillary spread in clinically node-negative breast cancer patients. On the other hand, axillary lymph node dissection (ALND) is the ideal procedure for patients with SLN metastasis. Different studies over the last few years have suggested that some patients with positive SLN can be treated without ALND. This article presents a literature review carried out by our multidisciplinary group and its strategy for avoiding routine ALND in women with SLN metastases. In this new strategy ALND should not be performed on women with T1 tumours, with 1-2 positive SLN and undergoing breast conservative surgery. On the other hand, ALND would be indicated in those patients with three or more positive SLN, presence of extracapsular invasion, mastectomised women and triple negative subtype or HER2+ tumours that have not received biological treatment with antibodies.

SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer (2022)

Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody–drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM (AU)

[Venous thrombosis of atypical location in patients with cancer]. / Trombosis venosa de localización atípica en pacientes con cáncer.

Venous thromboembolism (VTE) is a complication that frequently occurs in patients with neoplastic diseases. Several models have therefore been developed to identify patient subgroups diagnosed with cancer who are at increased risk of developing VTE. The most common forms of thromboembolic episodes are deep vein thrombosis in the lower limbs and pulmonary thromboembolism. However, venous thrombosis is also diagnosed in atypical locations. There are few revisions of unusual cases of venous thrombosis. In most cases, VTE occurs in the upper limbs and in the presence of central venous catheters, pacemakers and defibrillators. We present the case of a patient diagnosed with breast cancer and treated with surgery, chemotherapy and radiation therapy who developed a thrombosis in the upper limbs (brachial and axillary).

Recaídas locorregionales tras mastectomías preservadoras y reconstrucción inmediata en mujeres con cáncer de mama / Locoregional relapse after sparing mastectomies and immediate reconstruction in women with breast cancer

Introducción: Durante los últimos años, los cambios culturales de la sociedad actual y la mejora en la valoración del riesgo han incrementado la indicación de las mastectomías en mujeres con cáncer de mama. Diversos estudios han confirmado la seguridad oncológica de la mastectomías preservadoras y reconstrucción inmediata. El objetivo de este estudio es analizar la incidencia de recaídas locorregionales de este procedimiento y su impacto en la reconstrucción y la supervivencia global. Pacientes y métodos: Estudio prospectivo de pacientes con un carcinoma de mama que realizaron una mastectomía preservadora y reconstrucción inmediata. Se analizaron las recaídas locorregionales, el tratamiento de las mismas y la capacidad de preservar la reconstrucción, así como su impacto en la supervivencia. Resultados: El grupo a estudio lo constituyen 271 mujeres con carcinoma mamario tratadas mediante una mastectomía ahorradora de piel y reconstrucción inmediata. El seguimiento medio fue de 7,98 años y durante el mismo se diagnosticaron 18 recaídas locorregionales (6,6%): 72,2% en el colgajo de la mastectomía y 27,8% ganglionares. No se evidenciaron diferencias significativas en las características patológicas del tumor primario entre las pacientes con y sin una recaída locorregional, aunque el porcentaje de mujeres con tumores hormonosensibles fue superior en el grupo sin recaída. Las pacientes con recaída ganglionar presentaban tumores de mayor tamaño (el 80% T2-T3) y el 60% tenían metástasis axilares al diagnóstico vs. 7,7% de las mujeres con recaída en piel (p = 0,047). Todas las pacientes intervenidas de una recaída locorregional preservaron su reconstrucción. La incidencia de metástasis y muertes fue significativamente mayor en las pacientes con una recaída, causando una disminución no significativa de la supervivencia global. (AU)

Introduction: In recent years, cultural changes in today's society and improved risk assessment have increased the indication for mastectomies in women with breast cancer. Various studies have confirmed the oncological safety of sparing mastectomies and immediate reconstruction. The objective of this study is to analyze the incidence of locoregional relapses of this procedure and its impact on reconstruction and overall survival. Patients and methods: Prospective study of patients with breast carcinoma who underwent a sparing mastectomy and immediate reconstruction. Locoregional relapses and their treatment and their impact on survival were analyzed. Results: The study group is made up of 271 women with breast carcinoma treated with a skin-sparing mastectomy and immediate reconstruction. The mean follow-up was 7.98 years and during the same 18 locoregional relapses (6.6%) were diagnosed: 72.2% in the mastectomy flap and 27.8% lymph node. There were no significant differences in the pathological characteristics of the primary tumor between patients with and without locoregional relapse, although the percentage of women with hormone-sensitive tumors was higher in the group without relapse. Patients with lymph node relapse had larger tumors (80% T2–T3) and 60% had axillary metastases at diagnosis, compared to 7.7% of women with skin relapse (p = 0.047). All patients operated on for locoregional relapse preserved their reconstruction. The incidence of metastases and deaths was significantly higher in patients with a relapse, causing a non-significant decrease in overall survival. (AU)

Repercusión de los criterios ACOSOG Z0011 sobre la indicación de la linfadenectomía axilar y el control locorregional en mujeres con ganglio centinela metastásico. Resultados preliminares tras cuatro años de aplicación clínica / Repercussion of the ACOSOG-Z0011 criteria for the indication of axillary lymph node dissection and locoregional control in women with metastatic sentinel lymph node. Preliminary results after four years of clinical application

Objetivo. Evaluar los cambios en la indicación de la linfadenectomía axilar (LA), su eficacia para eliminar enfermedad residual y control locorregional, tras la adopción de los criterios del estudio ACOSOG Z0011. Pacientes y método. Estudio observacional retrospectivo en mujeres con carcinoma infiltrante de mama tratadas quirúrgicamente, entre febrero 2010 y mayo de 2014. Todas las pacientes fueron valoradas según los criterios del ensayo clínico ACOSOG Z0011 para el manejo del ganglio centinela (GC) metastatizado. Resultados. Un total de 118 enfermas presentaron afectación del GC, y de ellas 53 (44,92% de las pacientes con GC metastásico) evitaron la LA por la aplicación de los criterios ACOSOG Z0011. La mayoría de estas mujeres (73,58%) presentaron afectación micrometastásica del GC. El grupo de enfermas con mayor beneficio fueron las pacientes con conservación mamaria, ya que el 58,23% de estas enfermas evitaron la LA. Se realizaron un total de 65 LA por afectación metastásica del GC sin que se evidenciase metástasis en la grasa axilar en 37 (55,2%) pacientes. Conclusiones. La adopción de los criterios ACOSOG Z0011 permite disminuir la indicación de la LA, especialmente en aquellas mujeres sometidas a un procedimiento conservador. A pesar de la introducción de estos criterios, existe un grupo significativo de mujeres (55%) en quienes la LA no demuestra afectación ganglionar de la grasa axilar y no obtienen ningún beneficio con la misma (AU)

Objective. To evaluate changes in the indication of axillary lymph node dissection (ALND), its effectiveness in eliminating residual disease, and locoregional control after the adoption of the ACOSOG Z0011 study criteria. Patients and methods. Retrospective study in women with invasive breast cancer treated surgically from February 2010 to May 2014. All women were evaluated according to the ACOSOG-Z0011 trial criteria for the management of metastasized sentinel lymph node (SLN). Results. A total of 118 women had SLN involvement. Application of the ACOSOG Z0011 criteria avoided ALND in 53 of the 118 patients (44.92% of the patients with metastatic SLN), most of them (73.58%) with micrometastases. The benefit was greater in women undergoing conservative surgery, because 58.23% of these women avoided ALND. A total of 65 ALND were performed for metastatic SLN, of which 37 (55.2%) showed no involvement of axillary fat. Conclusions. Adoption of the ACOSOG Z0011 criteria decreases the indication of ALND, especially in women undergoing conservative surgery. Despite the introduction of these criteria, there is a significant percentage of women (55%) in whom ALND shows no lymph node involvement in axillary fat and produces no benefit (AU)

Angiosarcoma radioinducido de mama en paciente con síndrome de Li-Fraumeni / Radiation-induced angiosarcoma of the breast in a Li-Fraumeni patient

No disponible

Evaluación de un programa de reconstrucción mamaria inmediata mediante expansión-prótesis en mujeres con cáncer de mama / Evaluation of an immediate tissue expander-implant breast reconstruction program in women with breast cancer

Introducción. La reconstrucción mamaria inmediata mediante expansor-prótesis constituye una alternativa en la cirugía del cáncer de mama que precisa mastectomía. El objetivo de este estudio es analizar el impacto asistencial de este procedimiento y su eficacia para la reconstrucción mamaria. Pacientes y método. El grupo a estudio fueron pacientes intervenidas quirúrgicamente de cáncer de mama, por un mismo cirujano, entre enero de 2009 y diciembre de 2012, y a quienes se realizó mastectomía y reconstrucción inmediata con expansor-prótesis. Se excluyeron todas aquellas pacientes con reconstrucción diferida o autóloga, así como a las que se realizó mastectomía profiláctica. Las variables analizadas fueron: edad, tiempo quirúrgico, estancia hospitalaria, retraso en el inicio de quimioterapia, complicaciones, reintervenciones, características histopatológicas del tumor y afectación ganglionar, comparándose, mediante un estudio prospectivo no aleatorizado, con un grupo control, constituido por pacientes intervenidas mediante una cirugía conservadora o mastectomía sin reconstrucción. Resultados. Se incluyeron 69 pacientes en el grupo a estudio y 312 pacientes en el grupo control. El análisis comparativo entre el grupo a estudio y control no mostró diferencias significativas en las demoras asistenciales, el inicio del tratamiento adyuvante y las complicaciones postoperatorias, aunque sí en el tiempo quirúrgico y la estancia hospitalaria. Un total de 61 pacientes (88,4%) finalizaron la expansión y 53 (76,8%) acabaron con éxito su reconstrucción mamaria. El análisis por grupos de tratamiento demostró que el mayor éxito del procedimiento se consiguió en las pacientes sin tratamientos adyuvantes (100%), mientras que las pacientes con tratamiento quimioterápico y radioterápico presentaron la menor tasa de éxito (80%). Conclusión. La reconstrucción mamaria inmediata mediante expansor-prótesis es un procedimiento que precisa mayor tiempo quirúrgico y estancia hospitalaria respecto a otras técnicas oncológicas de la mama. La mayoría de las pacientes culminarán con éxito el proceso reconstructivo, aunque existirá una mayor tasa de fracaso en las pacientes irradiadas

Introduction. Immediate breast reconstruction with an expander-implant is an alternative in breast cancer surgery in patients requiring mastectomy. The objective of this study was to analyze the welfare impact of this procedure and its effectiveness in breast reconstruction. Patients and method. The study group consisted of patients treated for breast cancer who underwent mastectomy and immediate reconstruction with an expander-implant. All patients were treated by a single surgeon between January 2009 and December 2012. We excluded all patients with delayed or autologous reconstruction and prophylactic mastectomy. The variables analyzed were age, operating time, length of hospital stay, delayed initiation of chemotherapy, complications, reoperations, histopathologic features of the tumor, and lymph node involvement. These variables were compared in a prospective non-randomized study with those in a control group consisting of patients who underwent conservative surgery or mastectomy without reconstruction. Results. There were 69 patients in the study group and 312 patients in the control group. Comparison between the study and the control group showed no significant differences in healthcare delays, the start of adjuvant therapy, or postoperative complications, but differences were found in operating time and length of hospital stay. Expansion was completed in 61 patients (88.4%) and breast reconstruction in 53 (76.8%). Analysis by treatment groups showed that greater procedural success was achieved in patients without adjuvant treatments (100%), while patients with chemotherapy and radiotherapy had the lowest success rate (80%). Conclusion. Immediate breast reconstruction with an expander-implant requires longer operating time and hospital stay than other techniques in breast oncology. Most patients will successfully complete the reconstructive process, but the failure rate will be higher in irradiated patients

Trombosis venosa de localización atípica en pacientes con cáncer / Venous thrombosis of atypical location in patients with cancer

La enfermedad tromboembólica venosa (ETEV) es una complicación que se presenta con frecuencia en los pacientes con enfermedades neoplásicas; por ello se han desarrollado varios modelos para identificar subgrupos de pacientes diagnosticados de cáncer con riesgo aumentado de desarrollar ETEV. Las localizaciones más frecuentes de los episodios tromboembólicos son la trombosis venosa profunda en miembros inferiores y la tromboembolia pulmonar, sin olvidar que se diagnostican trombosis venosas en localizaciones atípicas. Apenas hay revisiones sobre trombosis venosas inusuales; en la mayoría de los casos, la localización más frecuente es en miembros superiores y en relación con la presencia de catéteres venosos centrales, marcapasos y desfibriladores. Presentamos el caso de una paciente diagnosticada de cáncer de mama y tratada con cirugía, quimioterapia y radioterapia que presentó una trombosis en miembros superiores (humeral y axilar) (AU)

Venous thromboembolism (VTE) is a complication that frequently occurs in patients with neoplastic diseases. Several models have therefore been developed to identify patient subgroups diagnosed with cancer who are at increased risk of developing VTE. The most common forms of thromboembolic episodes are deep vein thrombosis in the lower limbs and pulmonary thromboembolism. However, venous thrombosis is also diagnosed in atypical locations. There are few revisions of unusual cases of venous thrombosis. In most cases, VTE occurs in the upper limbs and in the presence of central venous catheters, pacemakers and defibrillators. We present the case of a patient diagnosed with breast cancer and treated with surgery, chemotherapy and radiation therapy who developed a thrombosis in the upper limbs (brachial and axillary) (AU)

Propuesta de una nueva estrategia terapéutica multidisciplinar en la mujer con cáncer de mama y afectación del ganglio centinela / Proposal for a new multidisciplinary therapeutic strategy in the breast cancer patient with sentinel lymph node metastasis

La biopsia de ganglio centinela (GC) es la técnica de elección para el estudio de extensión de la axila en la mujer con cáncer de mama sin afectación ganglionar. Por el contrario, la linfadenectomía axilar (LA) constituye el procedimiento idóneo para las pacientes con afectación metastásica del GC. Durante los últimos años diferentes estudios han sugerido que algunas pacientes con afectación del GC pueden ser tratadas sin LA. Este artículo expone la revisión bibliográfica realizada por nuestro grupo multidisciplinar y su estrategia para la supresión de la LA en mujeres con afectación metastásica del GC. En esta nueva estrategia la LA no se llevaría a cabo en mujeres con tumores T1, con afectación de 1-2 GC e intervenidas mediante una técnica quirúrgica conservadora. Por el contrario, se indicaría la LA en aquellas pacientes con tres o más GC afectados, invasión extracapsular del GC, mujeres mastectomizadas y tumores del subtipo triple negativo o HER2+ que no reciban tratamiento biológico con anticuerpos (AU)

Sentinel lymph node (SLN) biopsy is the standard of practice for assessing axillary spread inclinically node-negative breast cancer patients. On the other hand, axillary lymph no dedissection (ALND) is the ideal procedure for patients with SLN metastasis. Different studies over the last few years have suggested that some patients with positive SLN can be treated without ALND. This article presents a literature review carried out by our multidisciplinary group and its strategy for avoiding routine ALND in women with SLN metastases. In this new strategy ALND should not be performed on women with T1 tumours, with 1-2 positive SLN and undergoing breast conservative surgery. On the other hand, ALND would be indicated in those patients with three or more positive SLN, presence of extracapsular invasion, mastectomised women and triple negative subtype or HER2+ tumours that have not received biological treatment with antibodies (AU)