Biomarkers in breast cancer 2024: an updated consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

This revised consensus statement of the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathological Anatomy (SEAP) updates the recommendations for biomarkers use in the diagnosis and treatment of breast cancer that we first published in 2018. The expert group recommends determining in early breast cancer the estrogen receptor (ER), progesterone receptor (PR), Ki-67, and Human Epidermal growth factor Receptor 2 (HER2), as well as BReast CAncer (BRCA) genes in high-risk HER2-negative breast cancer, to assist prognosis and help in indicating the therapeutic options, including hormone therapy, chemotherapy, anti-HER2 therapy, and other targeted therapies. One of the four available genetic prognostic platforms (Oncotype DX®, MammaPrint®, Prosigna®, or EndoPredict®) may be used in ER-positive patients with early breast cancer to establish a prognostic category and help decide with the patient whether adjuvant treatment may be limited to hormonal therapy. In second-line advanced breast cancer, in addition, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and estrogen receptor 1 (ESR1) should be tested in hormone-sensitive cases, BRCA gene mutations in HER2-negative cancers, and in triple-negative breast cancer (TNBC), programmed cell death-1 ligand (PD-L1). Newer biomarkers and technologies, including tumor-infiltrating lymphocytes (TILs), homologous recombination deficiency (HRD) testing, serine/threonine kinase (AKT) pathway activation, and next-generation sequencing (NGS), are at this point investigational.

Pain in Long-Term Cancer Survivors: Prevalence and Impact in a Cohort Composed Mostly of Breast Cancer Survivors.

Cancer survival is becoming more common which means that there is now a growing population of cancer survivors, in whom pain may be common. However, its prevalence has hardly been addressed systematically. We aimed to assess the prevalence and explore the pathophysiology and impact of pain on health outcomes in cancer survivors. We conducted a retrospective-prospective cohort study in cancer-free patients diagnosed with cancer at least five years before the study start date. We used multivariable regression to establish the association of patients' cancer characteristics with pain, and then the association of patients' pain features with health outcomes and related symptoms. Between March and July 2021, 278 long-term cancer survivors were evaluated. Almost half of them (130/278, 46.8%) had pain, of whom 58.9% had a probable neuropathic component, but only 18 (13.8%) were taking specific drugs for neuropathic pain. A history of surgery-related pain syndrome in breast cancer patients was more than twice as frequent in the pain cohort. Post-chemotherapy and post-radiotherapy pain syndromes were uncommon. Pain was associated with lower QoL, emotional functioning, professional performance, and disability scores. Pain is a frequent health determinant in cancer survivors. Referral to specialised pain services may be a reasonable move in some cases.

Excess weight and anti-PD-1 immune checkpoint inhibitor’s outcomes in non-small cell lung cancer

Immune checkpoint inhibitors are one of the most effective treatments available in advanced non-small cell lung cancer. However, at present, there are no clinical or analytical biomarkers that define which patients benefit with certainty from these treatments. In our study, we evaluated whether excess weight could be a good predictive biomarker of benefit from these drugs.MethodsWe studied a population of 79 patients, divided into a study group with 39 patients diagnosed with non-small cell lung cancer treated with immunotherapy and 40 patients in a control group, diagnosed with different advanced cancers, treated with non-immunotherapy treatment. We analyzed according to the presence of excess weight or not, the treatment’s outcome in the study group and in the control group (objective response, and progression-free and overall survival).ResultsIn our study, we detected a better response rate to immunotherapy in patients with excess weight (62.50 vs 26.08%, OR 4.72, p = 0.02), and a better median progression-free survival (14.19 vs 5.03 months, HR 0.50, p = 0.058) and median overall survival (33.84 months vs 20.76 months, HR 0.43, p = 0.01) in the study group. These findings were specific to the immunotherapy group since in the control group, with patients who did not receive immune checkpoint inhibitors, these findings were not found.ConclusionOur study suggests that patients with excess weight who receive anti-PD-1 immune checkpoint inhibitors diagnosed with non-small cell lung cancer have a better outcome. This effect is specific to patients receiving immunotherapy. (AU)

Nivolumab-induced thyroid dysfunction in patients with lung cancer / Disfunción Tiroidea Inducida Por Nivolumab En Pacientes Con Cáncer

Background: Nivolumab is an anti-cancer monoclonal antibody that inhibits PD1 and modulates T-cell response. It has been shown to significantly improve survival in several types of cancer, but clinical trials have also reported an increased risk of developing immune-related adverse events (IRAEs). Endocrine IRAEs may be particularly relevant. Objective: To comprehensively evaluate the clinical presentation of endocrine IRAEs in patients with lung cancer treated with nivolumab. Potential risk factors are analyzed, and strategies for IRAE management are proposed. Methods: Forty consecutive patients treated with nivolumab for advanced non-small cell lung cancer (NSCLC) were studied, paying particular attention to development of endocrine IRAEs (thyroid, hypophyseal, adrenal, or pancreatic) and clinical outcome. Results: Thyroid function changes were found in 9 patients (22.5%), of which six developed hypothyroidism and three had hyperthyroidism after a median of 3.8 and 2.3 cycles of nivolumab respectively. Only one patient had thyroid-related symptoms. Thyroid autoimmunity was negative in all cases. Hyperthyroid patients showed no uptake in iodine scintigraphy, and their hormone values returned to normal in less than six months. Nivolumab was discontinued for toxicity in one patient. One patient with hyperthyroidism also developed autoimmune diabetes, and one patient with hypothyroidism also had hypogonadism. After a median follow-up of 7.6 months, 25 patients (62.5%) showed response to nivolumab. Univariate and multivariate analyses showed no differences between patients who developed thyroid changes and those who did not. Conclusions: Thyroid changes after treatment with nivolumab are common and warrant active laboratory monitoring. The underlying mechanisms and their relevance deserve further research

Introducción: Nivolumab es un anticuerpo monoclonal que ejerce acción anti-tumoral mediante la inhibición de PD1 y modulación de la respuesta de las células T. Ha demostrado un aumento significativo en la supervivencia de distintos tipos de cáncer, pero también se ha reportado un incremento en el riesgo de desarrollar eventos adversos relacionados con la inmunidad (IRAEs). Los IRAEs endocrinos son particularmente relevantes. Objetivos: Evaluar de forma detallada la presentación clínica de los IRAEs endocrinos en pacientes con cáncer de pulmón refractario tratados con nivolumab. Se analizan potenciales factores de riesgo y se proponen estrategias para su manejo. Material y métodos: Se estudiaron 40 pacientes consecutivos con cáncer de pulmón de células no pequeñas (NSCLC) tratados con nivolumab. Se realizó el seguimiento prestando especial atención al desarrollo de los IRAEs endocrinos (tiroides, hipófisis, adrenal o páncreas) y su evolución clínica. Resultados: Se detectaron alteraciones de la función tiroidea en 9 casos (22,5%): 6 hipotiroidismo y 3 hipertiroidismo, tras una mediana de 3,8 y 2,3 ciclos de nivolumab, respectivamente. Solo un paciente desarrolló síntomas relacionados. La autoinmunidad tiroidea fue negativa en todos los casos. La gammagrafía fue negativa en todos los casos de hipertiroidismo y los valores hormonales volvieron a la normalidad en menos de 6 meses. Se suspendió nivolumab en un caso debido a toxicidad. Uno de los pacientes con hipertiroidismo también desarrolló diabetes autoinmune, y uno de los pacientes con hipotiroidismo también presentaba hipogonadismo. Tras una mediana de seguimiento de 7,6 meses, 25 pacientes (62,5%) presentaron respuesta favorable al nivolumab. El análisis uni y multivariante no mostró diferencias entre los pacientes que desarrollaron alteraciones tiroideas y los que no. Conclusiones: Las alteraciones tiroideas tras el tratamiento con nivolumab son frecuentes y requieren una vigilancia activa. Los mecanismos subyacentes y su relevancia aún no se conocen en profundidad

Consenso de la Sociedad Española de Anatomía Patológica y la Sociedad Española de Oncología Médica sobre biomarcadores en cáncer de mama / Consensus statement on biomarkers in breast cancer by the Spanish Society of Pathology and the Spanish Society of Medical Oncology

En este consenso se revisan y actualizan las recomendaciones para el uso de biomarcadores en el diagnóstico y tratamiento del cáncer de mama, de forma conjunta con la Sociedad Española de Anatomía Patológica (SEAP) y la Sociedad Española de Oncología Médica (SEOM). Este grupo de expertos recomienda determinar en todos los casos de cáncer de mama el grado histológico, los receptores de estrógeno (RE)-alfa, los receptores de progesterona, el Ki-67 y el HER2 para evaluar el pronóstico y establecer las opciones terapéuticas, incluyendo hormonoterapia, quimioterapia y tratamiento anti-HER2. En las pacientes con RE-positivos y ganglios negativos se puede realizar una de las cuatro plataformas genéticas disponibles (MammaPrint®, Oncotype DX®, Prosigna® o EndoPredict®) para establecer una categoría de pronóstico y decidir con la paciente si el tratamiento adyuvante puede limitarse a la hormonoterapia. Las tecnologías más recientes, como la secuenciación de nueva generación, la biopsia líquida, la determinación de linfocitos infiltrados en el tumor o la determinación de PD-1, están por ahora en fase experimental (AU)

This consensus statement is a joint initiative of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM). It revises and updates the recommendations for the use of biomarkers in the diagnosis and treatment of breast cancer. The group of experts recommends that, in all cases of breast cancer, the histologic grade and the alpha-estrogen receptor (ER), progesterone receptor, Ki-67 and HER2 status should be determined, in order to assist prognosis and establish therapeutic options, including hormone therapy, chemotherapy and anti-HER2 therapy. One of the four available genetic prognostic platforms (MammaPrint®, Oncotype DX®, Prosigna® or EndoPredict®) may be used in node-negative ER-positive patients to establish a prognostic category and decide, together with the patient, whether adjuvant treatment be limited to hormonal therapy. Newer technologies, including next generation sequencing, liquid biopsy, tumour infiltrating lymphocytes or PD-1 determination, are still investigational (AU)

Grupo de Trabajo Interdisciplinar sobre Biomarcadores en Cáncer SEAP-SEOM: presentación y objetivos / Interdisciplinary Work Group on Biomarkers in Cancer SEAP-SEOM: presentation and objectives

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Complicaciones de unas metástasis intramusculares en un paciente con cáncer de pulmón / Complications of intramuscular metastasis in a patient with lung cancer

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Consenso de la Sociedad Española de Anatomía Patológica (SEAP) y de la Sociedad Española de Oncología Médica (SEOM) sobre la determinación de HER2 en el carcinoma gástrico / HER2 evaluation in gastric carcinoma: A consensus study by the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM)

La identificación de los carcinomas gástricos avanzados con alteraciones de HER2 es esencial en la práctica clínica diaria, ya que estas neoplasias requieren un tratamiento específico con trastuzumab. Por estos motivos, patólogos y oncólogos expertos en carcinoma gástrico y en la determinación de HER2, en representación de las sociedades respectivas (SEAP y SEOM), han trabajado para debatir y consensuar las recomendaciones nacionales de determinación de HER2 en los carcinomas gástricos. Estas recomendaciones se basan no sólo en la experiencia de los participantes en el consenso, sino también en la experiencia internacional publicada. En este consenso se muestran los requisitos mínimos que un laboratorio de anatomía patológica debe cumplir para garantizar la adecuada determinación de HER2 en la práctica diaria. Los laboratorios que carezcan de los estándares mínimos expuestos en esta guía deberían trabajar en alcanzarlo(AU)

The identification of HER2 alterations in advanced gastric carcinomas is critically important in daily clinical practice as such neoplasms require specific treatment with Trastuzumab. For this reason, expert pathologists and oncologists have agreed on national guidelines for HER2 testing in gastric carcinomas. The guidelines are based on the experience of the participants and pertinent recent international publications. They outline the minimum requirements for the Pathology Laboratory in order to guarantee satisfactory routine HER2 testing. The guidelines recommend that any laboratory not fulfilling such requirements make the adjustments necessary for compliance(AU)

Recomendación para la determinación de HER2 en cáncer de mama. Consenso nacional de la Sociedad Españolade Anatomía Patológica (SEAP) y de la SociedadEspañola de Oncología Médica (SEOM) / Guidelines for HER2 testing in breast cancer. A national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

La identificación de los carcinomas de mama con amplificación/sobreexpresión de HER2 es crítica en la práctica clínicadiaria ya que estas neoplasias requieren un tratamientoespecífico que incluye el uso de terapias dirigidas. Tanto lastécnicas de hibridación in situ como las técnicas inmunohistoquímicasson métodos apropiados para la identificación decánceres de mama HER2 positivos. Sin embargo, numerososestudios, incluidos los desarrollados por la Asociación para laGarantía de Calidad en Patología de la SEAP (AGCP) y laexperiencia de centros de referencia nacionales en la determinaciónde HER2 han puesto de manifiesto importantesproblemas de reproducibilidad entre laboratorios. Por estosmotivos, patólogos expertos en la determinación de HER2 deestos centros de referencia, así como oncólogos médicos conuna contrastada actividad en cáncer de mama, en representaciónde las sociedades respectivas (SEAP y SEOM), han trabajadopara debatir y consensuar las recomendaciones nacionalesde determinación de HER2. Estas recomendaciones sebasan no sólo en la experiencia de los participantes en el consenso, sino también en la experiencia internacional publicadaen recientes guías de distintos países, tales como EstadosUnidos, Reino Unido y Canadá.En este consenso, se recomiendan los requisitos mínimosque un laboratorio de Anatomía Patológica debe cumplirpara garantizar la adecuada determinación de HER2 enla práctica diaria. Aquellos laboratorios que carezcan de losestándares mínimos expuestos en esta guía deberían trabajaren alcanzarlos y durante este proceso remitir a laboratoriosde referencia las muestras en las que la determinaciónde HER2 tenga implicaciones clínicas para las pacientes (AU)

Breast cancers with HER2 alterations are critical toidentify because such tumors require unique treatment,including the use of targeted therapies. HER2 alterationsat the DNA (amplification) and protein (overexpression)level usually occur in concert, and both in situ hybridizationand immunohistochemistry can be accurate methodsto assess these alterations. However, recent studies includingthose conducted by the Association for QualityAssessment of the Spanish Society of Pathology and theexperience of several national reference centres for HER2testing have suggested that serious reproducibility issuesexist with both techniques. To address this, a joint committeeof both the Spanish Society of Pathology and theSpanish Society of Medical Oncology has met to reviewguidelines for HER2 testing. Consensus recommendationare based not only on panellist’s experience but also inthose consensus guidelines previously reported in severalcountries, such as United Stated, United Kingdom andCanada . These guidelines include minimal requirements thatPathology Department must meet in order to guaranteeappropriate HER2 testing in breast cancer. Pathology laboratoriesthat do not meet these standards must put effort toreach them and, in the meantime, send clinical cases to referencecentres (AU)

Sintasa de ácidos grasos como nueva diana antitumoral / Fatty acid synthase: a new anti-tumor target

La sintasa de ácidos grasos (FASN), enzima que produce la síntesis de novo de ácidos grasos, está sobreexpresada e hiperactivada en la mayoría de los carcinomas humanos. Estudios clínicos han demostrado que la sobreexpresión de FASN conlleva un mal pronóstico en cáncer de mama y próstata, y su inhibición es selectivamente citotóxica en células tumorales humanas. Por todo ello, FASN y el metabolismo de los ácidos grasos está resultando de especial interés para el diagnóstico y el tratamiento del cáncer. Por dicho motivo, es imprescindible el desarrollo y la identificación de nuevos fármacos antitumorales inhibidores de FASN (AU)

Fatty acid synthase (FASN), an enzyme capable of de novo fatty acid synthesis, is highly expressed and activated in most human carcinomas. FASN is associated with poor prognosis in prostate and breast cancer and its inhibition is selectively cytotoxic to human cancer cells. Thus, FASN and fatty acid metabolism have become an important focus for the diagnostic and treatment of cancer. In this sense, there is an increasing interest in identifying and developing new antitumor compounds that inhibit FASN (AU)

Vacunas y cáncer de mama / No disponible

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Serum endostatin and bFGF as predictive factors in advanced breast cancer patients treated with letrozole

Introduction. To investigate the value of baselineserum levels of VEGF, bFGF, endostatin and theirratio as predictive factors of response to endocrinetherapy in patients with metastatic breast cancer(MBC) and positive ER treated with letrozole aftertamoxifen failure.Materials and method. The serum levels of endostatin,VEGF and bFGF were determined in postmenopausalpatients with progressing MBC fromserum samples obtained before initiation of letrozole.The relation between serum angiogenic factorlevels and TTP was investigated.Results. Seventy-six patients (45.2%) presented ahigh endostatin level (> 24.6 ng/ml), 40% low bFGFlevels (0 pg/ml) and 50.4% low VEGF ( 24.6 ng/ml and bFGF equal 0 pg/mlwas 9.5 months versus 19.5 months in patients withendostatin 0 pg/ml.Conclusions. The baseline levels of bFGF and endostatinare predictive factors of efficacy in patientswith MBC treated with letrozole and can selectgroups with different TTP

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Mediterranean diet, olive oil and cancer

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Olive oil is an integral ingredient of the«Mediterranean diet» and accumulating evidencesuggests that it may have a potential role in loweringthe risk of several types of cancers. The mechanismsby which the carcer-preventing effects ofolive oil can be performed, however, are not known.We recently hypothesized that a novel molecularexplanation concerning the anti-cancer actions ofolive oil may relate to the ability of its monounsaturatedfatty acid (MUFA) oleic acid (OA; 18:1n-9) tospecifically regulate cancer-related oncogenes. Supportingour hypothesis, exogenous supplementationof cultured breast cancer cells with physiologicalconcentrations of OA was found to suppress theover expression of HER2 (Her-2/ neu, erbB-2), awell-characterized oncogene playing a key role inthe etiology, progression and response to che motherapy and endocrine therapy in approximately20% of breast carcinomas. OA treatment was alsofound to synergistically enhance the efficacy oftrastuzumab, a humanized monoclonal antibodybinding with high affinity to the ectodomain (ECD)of the Her2-coded p185HER2 oncoprotein. Moreover,OA exposure significantly diminished the proteolyticcleavage of the ECD of HER2 and, consequently,its activation status, a crucial molecular event thatdetermines both the aggressive behavior and the responseto trastuzumab of Her2-overexpressingbreast carcinomas. Our most recent findings furtherreveal that OA exposure may suppresses HER2 atthe transcriptional level by up-regulating the expressionof the Ets protein PEA3 -a DNA-bindingprotein that specifically blocks HER2 promoter activity-in breast, ovarian and stomach cancer celllines. This anti-HER2 property of OA offers a previouslyunrecognized molecular mechanism by whicholive oil may regulate the malignant behavior ofcancer cells. From a clinical perspective, it couldprovide an effective means of influencing the outcomeof Her-2/ neu-overexpressing human carcinomaswith poor prognosis. Indeed, OA-induced transcriptionalrepression of HER2 oncogene mayrepresent a novel genomic explanation linking «Mediterranean diet», olive oil and cancer as it seems toequally operate in various types of Her-2/ neu-relatedcarcinomas

Intersticial pneumonitis after oxaliplatin treatment in colorectal cancer

Progressive respiratory failure developed in a 68 year-old female who was treated with single-agent oxaliplatin for colorectal cancer. Only one cycle of 5-fluorouracil had been previously administered. Computed tomography of the chest showed lesions that suggested pulmonary fibrosis. There was an unfavourable response to treatment with corticosteroids, antimicrobial and antifungical agents. Lung biopsy findings were compatible with interstitial pneumonitis. The patient died 20 days after admission due to irreversible respiratory failure. This is the first case reported in the literature of interstitial pneumonitis related to single-agent oxaliplatin administration