Ribociclib plus Endocrine Therapy in Early Breast Cancer.

BACKGROUND: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear. METHODS: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy. RESULTS: As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points - distant disease-free survival and recurrence-free survival - also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals. CONCLUSIONS: Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.).

Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment. METHODS: We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres (hospitals and specialty cancer centres in Asia, Europe, USA, and Canada). Eligible participants were aged 18 years or older with centrally confirmed HER2-positive stage II-III operable breast cancer (>2 cm tumour size), an Eastern Cooperative Oncology Group performance status of 0-1, and a baseline left ventricular ejection fraction of at least 55% (by echocardiogram or multiple-gated acquisition scan). We randomly assigned participants (1:1) to receive either trastuzumab emtansine plus pertuzumab or docetaxel, carboplatin, and trastuzumab plus pertuzumab. We did the randomisation via an interactive response system under a permuted block randomisation scheme (block size of four), stratified by hormone receptor status, stage at diagnosis, and geographical location. Patients received six cycles (every 3 weeks) of neoadjuvant trastuzumab emtansine plus pertuzumab (trastuzumab emtansine 3·6 mg/kg; pertuzumab 840 mg loading dose, 420 mg maintenance doses) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (docetaxel 75 mg/m2; carboplatin area under the concentration-time curve 6 mg/mL × min; trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance doses) plus pertuzumab [same dosing as in the other group]). All treatments were administered intravenously. The primary objective was to compare the number of patients who achieved a pathological complete response (ypT0/is, ypN0), between groups in the intention-to-treat population (two-sided assessment), based on local evaluation of tumour samples taken at breast cancer surgery done between 14 days and 6 weeks after completion of neoadjuvant therapy. Safety was analysed in patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02131064, and follow-up of the adjuvant phase is ongoing. FINDINGS: Between June 25, 2014, and June 15, 2015, we randomly assigned 444 patients to neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221). A pathological complete response was achieved by 99 (44·4%) of 223 patients in the trastuzumab emtansine plus pertuzumab group and 123 (55·7%) of 221 patients in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group (absolute difference -11·3 percentage points, 95% CI -20·5 to -2·0; p=0·016). During neoadjuvant treatment, compared with patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab, fewer patients receiving trastuzumab emtansine plus pertuzumab had a grade 3-4 adverse event (29 [13%] of 223 vs 141 [64%] of 219) or a serious adverse event (11 [5%] of 223 vs 63 [29%] of 219). The most common grade 3-4 adverse events in the trastuzumab emtansine plus pertuzumab group were decreased platelet count (three [1%] of 223 patients vs 11 [5%] of 219 with docetaxel, carboplatin, and trastuzumab plus pertuzumab), fatigue (three [1%] vs seven [3%]), alanine aminotransferase increase (three [1%] vs four [2%]), and hypokalaemia (three [1%] vs five [2%]). The most common grade 3-4 adverse events in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group were neutropenia (55 [25%] of 219 vs one [<1%] of 223 with trastuzumab emtansine plus pertuzumab), diarrhoea (33 [15%] vs 2 [<1%]), and febrile neutropenia (33 [15%] vs 0). No deaths were reported during neoadjuvant treatment. INTERPRETATION: Traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade (docetaxel, carboplatin, and trastuzumab plus pertuzumab) resulted in significantly more patients achieving a pathological complete response than HER2-targeted chemotherapy plus HER2-targeted blockade (trastuzumab emtansine plus pertuzumab); however, numerically more grade 3-4 and serious adverse events occurred in the chemotherapy plus trastuzumab and pertuzumab group. Further efforts to improve the efficacy of chemotherapy without imparting more toxicity are warranted. FUNDING: F Hoffmann-La Roche and Genentech.

Imaging Radiation Doses and Associated Risks and Benefits in Subjects Participating in Breast Cancer Clinical Trials.

BACKGROUND: Medical imaging is commonly required in breast cancer (BC) clinical trials to assess the efficacy and/or safety of study interventions. Despite the lack of definitive epidemiological data linking imaging radiation with cancer development in adults, concerns exist about the risks of imaging radiation-induced malignancies (IRIMs) in subjects exposed to repetitive imaging. We estimated the imaging radiation dose and IRIM risk in subjects participating in BC trials. MATERIALS AND METHODS: The imaging protocol requirements in 10 phase III trials in the adjuvant and advanced settings were assessed to estimate the effective radiation dose received by a typical and fully compliant subject in each trial. For each study, the excess lifetime attributable cancer risk (LAR) was calculated using the National Cancer Institute's Radiation Risk Assessment Tool, version 3.7.1. Dose and risk calculations were performed for both imaging intensive and nonintensive approaches to reflect the variability in imaging performed within the studies. RESULTS: The total effective imaging radiation dose was 0.4-262.2 mSv in adjuvant trials and 26-241.3 mSv in metastatic studies. The dose variability resulted from differing protocol requirements and imaging intensity approaches, with computed tomography, multigated acquisition scans, and bone scans as the major contributors. The mean LAR was 1.87-2,410/100,000 in adjuvant trials (IRIM: 0.0002%-2.41% of randomized subjects) and 6.9-67.3/100,000 in metastatic studies (IRIM: 0.007%-0.067% of subjects). CONCLUSION: IRIMs are infrequent events. In adjuvant trials, aligning the protocol requirements with the clinical guidelines' surveillance recommendations and substituting radiating procedures with equivalent nonradiating ones would reduce IRIM risk. No significant risk has been observed in metastatic trials, and potential concerns on IRIMs are not justified. IMPLICATIONS FOR PRACTICE: Medical imaging is key in breast cancer (BC) clinical trials. Most of these procedures expose patients to ionizing radiation, and the risk of second cancer development after imaging has prompted recent concerns and controversy. Using accepted calculation models, the number of malignancies were estimated that were potentially attributable to the imaging procedures performed during a patient's participation in BC clinical trials. The results show that for patients participating in metastatic trials, the risk of imaging radiation-induced malignancies is negligible. In adjuvant trials, some second cancers due to imaging could be expected, and measures can be taken to reduce their risk.

Planning cancer control in Latin America and the Caribbean.

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.

Rationale and trial design of NATALEE: a Phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2- early breast cancer.

Background: Ribociclib has demonstrated a statistically significant overall survival benefit in pre- and postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) advanced breast cancer. New Adjuvant Trial with Ribociclib [LEE011] (NATALEE) is a trial evaluating the efficacy and safety of adjuvant ribociclib plus endocrine therapy (ET) versus ET alone in patients with HR+/HER2- early nonmetastatic breast cancer (EBC). Methods/design: NATALEE is a multicenter, randomized, open-label, Phase III trial in patients with HR+/HER2- EBC. Eligible patients include women, regardless of menopausal status, and men aged ⩾18 years. Select patients with stage IIA, stage IIB, or stage III disease (per the anatomic classification in the AJCC Cancer Staging Manual, 8th edition) with an initial diagnosis ⩽18 months prior to randomization are eligible. Patients receiving standard (neo)adjuvant ET are eligible if treatment was initiated ⩽12 months before randomization. Patients undergo 1:1 randomization to ribociclib 400 mg/day (3 weeks on/1 week off) +ET (letrozole 2.5 mg/day or anastrozole 1 mg/day [investigator's discretion] plus goserelin [men or premenopausal women]) or ET alone. Ribociclib treatment duration is 36 months; ET treatment duration is ⩾60 months. The primary end point is invasive disease-free survival. Discussion: The 36-month treatment duration of ribociclib in NATALEE is extended compared with that in other adjuvant cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor trials and is intended to maximize efficacy due to longer duration of CDK4/6 inhibition. Compared with the 600-mg/day dose used in advanced breast cancer, the reduced ribociclib dose used in NATALEE may improve tolerability while maintaining efficacy. NATALEE includes the broadest population of patients with HR+/HER2- EBC of any Phase III trial currently evaluating adjuvant CDK4/6 inhibitor treatment. Trial registration: ClinicalTrials.gov identifier: NCT03701334 (https://clinicaltrials.gov/ct2/show/NCT03701334).

Intensive Imaging Surveillance of Survivors of Breast Cancer May Increase Risk of Radiation-induced Malignancy.

BACKGROUND: Current clinical guidelines recommend mammography as the only imaging method for surveillance in asymptomatic survivors of early breast cancer (EBC). However, non-recommended tests are commonly used. We estimated the imaging radiation-induced malignancies (IRIM) risks in survivors of EBC undergoing different imaging surveillance models. MATERIALS AND METHODS: We built 5 theoretical models of imaging surveillance, from annual mammography only (model 1) to increasingly imaging-intensive approaches, including computed tomography (CT) scan, positron emission tomography-CT, bone scan, and multigated acquisition scan (models 2 through 5). Using the National Cancer Institute's Radiation Risk Assessment Tool, we compared the excess lifetime attributable cancer risk (LAR) for hypothetical survivors of EBC starting surveillance at the ages of 30, 60, or 75 years and ending at 81 years. RESULTS: For all age groups analyzed, there is a statistically significant increase in LAR when comparing model 1 with more intensive models. As an example, in a patient beginning surveillance at the age of 60 years, there is a 28.5-fold increase in the IRIM risk when comparing mammography only versus a schedule with mammography plus CT scan of chest-abdomen and bone scan. We found no differences when comparing models 2 through 5. LAR is higher when surveillance starts at a younger age, although the age effect was only statistically significant in model 1. CONCLUSION: Non-recommended imaging during EBC surveillance can be associated with a significant increase in LAR. In addition to the lack of survival benefit, additional tests may have significant IRIM risks and should be avoided.

EPIDEMIOLOGY AND TREATMENT OF MONTEGGIA LESION IN ADULTS: SERIES OF 44 CASES.

OBJECTIVE: To analyze the epidemiology, treatment and outcome of a series of adult patients with Monteggia lesion treated in Uruguayan institutions. METHODS: This is a retrospective article, we retrospectively identified from two Uruguayan institutions 44 adult patients with Monteggia lesion and analyzed their characteristics including Bado classification, associated injuries, treatment modality and outcome (Morrey score). RESULTS: Using Bado classification, 23 cases (52%) were type II, 12 (27%) type I, seven (16%) type IV and two cases (5%) type III. Associated lesions were radial head fractures, found in 15 patients, coronoid ipsilateral fractures in seven patients, and neurological injuries in four. Radial head dislocation was reduced in 93% of the cases with closed maneuvers. Ulna fractures underwent open reduction and internal fixation in all 30 cases using 3.5 mm DCP plates. Complications after surgery occurred in 21 cases. Revision surgery was done in 15 cases. Outcomes after primary and revision surgery were good or excellent in 37 cases. CONCLUSIONS: In our series we observed that Monteggia lesion in adults is a serious injury with a high number of complications that often require revision surgeries. Level of Evidence IV, Retrospective Study, Case Series.

Synchronous presentation of an Askin tumor and a plasmacytoma in an adult patient.

Askin tumor, or malignant small round cell tumor of the thoracopulmonary region, is an extremely infrequent entity occurring primarily in children and adolescents. Its histopathologic and cytogenetic features suggest that it belongs to the family of Ewing's sarcoma and primitive neuroectodermal tumors. We report the case of a 43-year-old woman affected by an Askin tumor with bone metastases at diagnosis, presenting synchronously with a plasmacytoma. This is the first reported case of the simultaneous occurrence of an Askin tumor and a malignant hemopathy. The progression of the former and the remission of the plasmacytoma during chemotherapy were remarkable, since Askin tumor treatment shares drugs used for the treatment of plasma cell tumors. Given the infrequent presentation of these diseases in a young adult and the coexistence of two neoplasias characterized by typical chromosomal abnormalities, we consider the possibility of a genetic cancer susceptibility in our patient.

EPIDEMIOLOGY AND TREATMENT OF MONTEGGIA LESION IN ADULTS: SERIES OF 44 CASES

ABSTRACT Objective: To analyze the epidemiology, treatment and outcome of a series of adult patients with Monteggia lesion treated in Uruguayan institutions. Methods: This is a retrospective article, we retrospectively identified from two Uruguayan institutions 44 adult patients with Monteggia lesion and analyzed their characteristics including Bado classification, associated injuries, treatment modality and outcome (Morrey score). Results: Using Bado classification, 23 cases (52%) were type II, 12 (27%) type I, seven (16%) type IV and two cases (5%) type III. Associated lesions were radial head fractures, found in 15 patients, coronoid ipsilateral fractures in seven patients, and neurological injuries in four. Radial head dislocation was reduced in 93% of the cases with closed maneuvers. Ulna fractures underwent open reduction and internal fixation in all 30 cases using 3.5 mm DCP plates. Complications after surgery occurred in 21 cases. Revision surgery was done in 15 cases. Outcomes after primary and revision surgery were good or excellent in 37 cases. Conclusions: In our series we observed that Monteggia lesion in adults is a serious injury with a high number of complications that often require revision surgeries. Level of Evidence IV, Retrospective Study, Case Series.

Cambios en la densidad mineral ósea en pacientes que reciben terapia de deprivación androgénica para el cáncer de próstata / Changes in bone mineral density in patients receiving androgen deprivation therapy for prostate cancer

Introducción: el cáncer de próstata (CP) es el tumor maligno más frecuente en hombres en Uruguay. La terapia de deprivación androgénica (TDA) es una herramienta valiosa para su tratamiento. Si bien es altamente eficaz, este tratamiento tiene diversos efectos no deseados, entre los que se encuentra la disminución de la densidad mineral ósea. Material y método: realizamos un estudio longitudinal, observacional y prospectivo cuyo objetivo fue determinar si existe disminución de la densidad mineral ósea en los pacientes que reciben TDA para el CP. Se incluyeron pacientes portadores de CP en cualquier estadio que iniciarían tratamiento con TDA en el Servicio de Oncología del Hospital de Clínicas de Montevideo, Uruguay, en el período setiembre de 2012 a agosto de 2013, en quienes se realizó una densitometría ósea (DMO) previo al inicio de la TDA (DMO1) y se repitió a los seis meses de recibir la primera dosis de tratamiento hormonal (DMO2). Para cada región analizada se compararon las medias de densidad ósea medida en g/cm2 en la DMO1 vs DMO2. Resultados: se hizo seguimiento a diez pacientes con una edad mediana de 77 años. Se observó disminución significativa de la densidad mineral ósea en vértebras L3 y L4 (L3: 1.268 g/cm2 a 1.225 g/cm2 p=0,01; L4: 1.247 g/cm2 a 1.227g/cm2 p=0,005), mientras que en los otros puntos evaluados (L1, L2, cuello de fémur y cadera total) también hubo una disminución pero sin alcanzar significancia estadística. Conclusiones: confirmamos que la TDA disminuye la densidad mineral ósea por lo menos en vértebras lumbares 3 y 4 en un relativamente corto plazo (seis meses). Este efecto adverso debe evaluarse, identificarse y prevenirse oportunamente para evitar complicaciones mayores.

Abstract Introduction: prostate cancer is the most frequent malignant tumor in men in Uruguay. Androgenic deprivation therapy (ADT) is a valuable tool to treat this condition. In spite of it being highly effective, this treatment has several non-desirable effects, a reduction in bone mineral density being among them. Material: we conducted a longitudinal, observational and prospective study whose objective was to determine whether there is a reduction in bone mineral density in patients who receive ADT for prostate cancer. Patients who were carriers of prostate cancer undergoing any stage who would start their ADT treatment at the Oncology Unit of the University Hospital of Montevideo from September 2012 through August 2013 were included in the study. All of them underwent a bone densitometry prior to the initiation of ADT (BD1) treatment and it was repeated six months after they received the first dose of hormone treatment (BD2). Measurements of bone density were compared for every region analysed in g/ cm2 in BD1 versus BD2. Results: Ten patients with an average age of 77 years old were followed-up. A significant reduction in bone mineral density was observed in the L3-L4 spinal segment (L3: 1.268 g/cm2 at 1.225 g/cm2 p=0.01; L4: 1.247g/cm2 at 1.227g/cm2 p=0.005), whereas in the other points assessed (L1, L2, femoral neck and total hip) there was a reduction as well, although it did not represent any statistical significance. Conclusions: we confirmed ADT reduces the bone mineral density in lumbar vertebrae L3 and L4 in a relatively short time (six minths). This negative effect needs to be timely assessed, identified and prevented to avoid greater complications.

Resumo Introdução: o câncer de próstata (CP) é o tumor maligno mais frequente em homens no Uruguai. A terapia de deprivação androgênica (TDA) é uma ferramenta valiosa para seu tratamento. Embora seja altamente eficaz, este tratamento apresenta diversos efeitos não desejados, entre eles a diminuição da densidade mineral óssea. Material e método: realizamos um estudo longitudinal, observacional e prospectivo cujo objetivo foi detectar uma possível redução da densidade mineral óssea em pacientes que recebem TDA para CP. Foram incluídos pacientes portadores de CP em qualquer estadio que iniciaram tratamento com TDA no Serviço de Oncologia do Hospital de Clínicas de Montevidéu, Uruguai, no período setembro de 2012 a agosto de 2013; antes do inicio do tratamento foi realizada una densitometria óssea (DMO1) e uma segunda seis meses depois da primeira dose de tratamento hormonal (DMO2). Para cada região analisada foram comparadas as medias de densidade óssea medida en g/cm2 na DM1 versus DMO2. Resultados: dez pacientes com um mediana de idade de 77 anos foram estudados. Observamos uma diminuição significativa da densidade mineral óssea nas vértebras L3 e L4 (L3: 1.268 g/cm2 a 1.225 g/cm2 p=0,01; L4: 1.247g/cm2 a 1.227g/cm2 p=0,005); em outros pontos avaliados (L1, L2, colo de fêmur e quadril total) também houve diminuição porém não era estatisticamente significativa. Conclusões: confirmamos que a TDA diminui a densidade mineral óssea pelo menos nas vértebras lombares 3 e 4 em um prazo relativamente curto (seis meses). Este efeito adverso deve ser avaliado, identificado e prevenido oportunamente para evitar maiores complicações.

Análisis de sobrevida según perfil biológico de pacientes uruguayas con cáncer de mama / Survival data analysis by biological profile of uruguayan patients with breast cancer

Introducción: el cáncer de mama (CM) constituye una enfermedad heterogénea reconociéndose subtipos con diferentes características mediante, entre otras técnicas, el estudio del nivel de expresión tumoral de los receptores hormonales (RRHH) y del HER2. Previamente reportamos la relación entre estos subtipos y características clínico-patológicas en pacientes uruguayas. Objetivo:analizar la sobrevida libre de enfermedad (SVLE) de pacientes uruguayas con cáncer de mama de acuerdo a su subtipo biológico, definido en base a la expresión tumoral de HER2 y RRHH evaluada mediante inmunohistoquímica. Material y método:se revisaron historias clínicas de pacientes intervenidas quirúrgicamente por CM estadios I-III en un período de dos años, realizándose el cálculo de SVLE para todas las pacientes y según subtipo biológico. Resultados:con seguimiento mediano de 40 meses, la SVLE a dos años para el total de las pacientes fue de 92,3%; 94% para las pacientes RRHH+/HER2-, 91% para las triple negativas (TN) y 71,4% para las HER2+. La comparación de las curvas de SVLE, según los diferentes subtipos, mostró menor SVLE para las pacientes HER2+ (p = 0,03) y similar SVLE de las pacientes RRHH+/HER2- y TN (p = 0,86). Conclusiones: las pacientes uruguayas con CM presentan una SVLE a dos años acorde a los reportes internacionales. Las pacientes HER2+ presentan una mayor tasa de recidivas,lo cual también es coincidente a lo reportado. La similar SVLE a dos años de las pacientes RRHH+/HER 2- y de las TN no se explicaría por diferencias en características clínico-patológicas, planteándose como hipótesis una mayor proporción de pacientes del subtipo luminal B entre las pacientes RRHH+/ HER 2-.

Introduction: breast cancer constitutes an heterogeneous disease. Two sub-types have been distinguished through the study of the tumor expression level of hormone receptors tumors, and level of HER2 expression, among other techniques. We previously reported therelation between these sub-types and the clinical and pathological characteristics of Uruguayan women.Objective: to analyse the disease-free survival (DFS) of Uruguayan patients with breast cancer, according to their biological sub-type, defined based on the tumor expression of hormone receptors and HER2 expression which were assessed by immune-histologicalchemistry staining. Method: all clinical records of patients who had undergone breast cancer surgery (Stages I-III) during a two year period were reviewed. The disease-free survival rate was calculated for all patients and according to their biological profile.Results: forty months follow up revealed disease-free survival upon two years of 92.3% for all patients;94% for hormone receptor positive /HER2 negative patients, 91% for triple negative patients, and 71.4% for hormone receptor positive patients.Comparing the DFS curves, for the different sub-types, evidenced a lower DFS for HER2+ patients (p = 0.03), and similar DFS for hormone receptor positive/HER2 negative and triple negative (p = 0.86). Conclusions:uruguayan patients with breast cancershow a two-year-DFS that matches international reports. HER2+ patients evidence a higher relapse rate, also consistent with international reports. Similar DFS upon two years, between hormone receptor positive/HER2 negative patients and triple negative patients cannot be due to differences in the clinical-pathologicalcharacteristics, thus a hypothesis is considered: there is a larger proportion of patients of the luminal B breast cancer sub-type among hormone receptor positive/HER2 negative patients.

Introdução: o câncer de mama (CM) é uma patologia heterogênea, apresentando subtipos com diferentes características determinadas, entre outras técnicas, pelo estudo do nível de expressão tumoral dos receptoreshormonais (RRHH) e do HER2. Em um artigo anterior descrevemos a relação entre esses subtipos e as características clínico-patológicas em pacientes uruguaias. Objetivo: analisar a sobrevida livre de enfermidade(SVLE) de pacientes uruguaias com CM de acordo a seu subtipo biológico, definido pela expressão tumoral deHER2 e RRHH avaliada por imunohistoquímica. Material e método:foram revisados os prontuários de pacientes operadas por cirurgia por CM estadios I-III em um período de dois anos; realizou-se o cálculo de SVLE de todas as pacientes e de acordo com o subtipo biológico. Resultados: o seguimento com uma mediana de 40meses mostrou uma SVLE aos dois anos para todas as pacientes de 92,3%; 94% para as pacientesRRHH+/HER2-, 91% para a triple negativa (TN) e 71,4% para as HER2+.A comparação das curvas de SVLE, segundo os diferentes subtipos, mostrou uma menor SVLE para as pacientes HER2+ (p = 0,03) e similar SVLE para as pacientes RRHH+/HER2- y TN (p = 0,86). Conclusões: as pacientes uruguaias com CM apresentam uma SVLE a dois anos compatível com resultados internacionais. As pacientes HER2+ apresentaram uma taxa maior de recidivas, resultados que coincidemcom resultados internacionais. A SVLE aos dois anos similar para pacientes RRHH+/HER2- e TN não pode serexplicada pelas diferenças nas características clínico-patológicas, considerando-se como hipótese umaproporção maior de pacientes do subtipo luminal B entre as pacientes RRHH+/HER2-.

Expresión tumoral de HER-2, receptores de estrógenos y de progesterona y su relación con características clínico-patológicas en pacientes uruguayas con cáncer de mama / Tumor expression of HER-2, estrogen and progesterone receptors and their relationship with clinical-pathological characteristics in Uruguayan patients with breast cancer

Introducción: el cáncer de mama (CM), principal causa de muerte por cáncer en la mujer uruguaya, constituye una enfermedad heterogénea. El estudio de la expresión tumoral del receptor del factor de crecimiento epidérmico-2 (HER2), el receptor de estrógenos (RE) y el receptor de progesterona (RP) permite reconocer subtipos con diferentes características clínico-patológicas y evolutivas. Objetivos: conocer el perfil de expresión tumoral de HER2, RE y RP y su relación con características clínico-patológicas en pacientes uruguayas con CM. Material y método: se revisaron las historias clínicas de pacientes intervenidas quirúrgicamente por CM invasivo en un período de dos años, seleccionándose las que contaban con la determinación de RE, RP y HER2 mediante inmunohistoquímica. Se comparó el perfil de expresión de estos marcadores con la edad al diagnóstico, tipo y grado histológico (GH) y estadio patológico (TNM). Resultados: se seleccionaron 197 pacientes cuyas características fueron edad media: 55 años, carcinoma ductal: 85%, GH 1-2: 59%, estadio: I-II: 75%, metástasis axilares: 51%, RE/RP+: 78%, HER2+: 10%. Se definieron tres subtipos: HER2- RE/RP+ (73%), HER2+ (10%) y triple negativo (TN) (17%). Los subtipos TN y HER2+ se asociaron con mayor grado histológico (p<0,05) y el TN con menor edad al diagnóstico (p<0,05) que el subtipo HER2-, RE/RP+. Conclusiones: el porcentaje de pacientes con CM invasivo subtipo HER2+ (10%) es menor que el reportado por otros estudios (17%-28%). En concordancia con estudios previos, los subtipos TN y HER2+ se correlacionaron con tumores más indiferenciados y el TN se presentó en pacientes más jóvenes

Summary Introduction: breast cancer, the main cause of death of Uruguayan women, is an heterogeneous disease. Study of the tumoral expression of the Human Epidermal growth factor Receptor-2 (HER2), the estrogen receptor and the progesterone receptor enables the recognition of sub-types with different clinical, and pathological characteristics and evolution. Objectives: to learn about the HER2, estrogen receptor and progesterone receptor tumoral expression profile and their relationship with clinical-pathological characteristics in Uruguayan patients with breast cancer. Method: we reviewed the medical record of patients who underwent surgery for invasive breast cancer within a two year period, and we selected those who had determination of estrogen receptor, progesterone receptor and HER2 through immune-histochemestry. We compared the expression profile of these markers with the age at the time of diagnosis, the histological type and degree and the pathological status. Results: we selected 197 patients with the following characteristics: average age: 55 years old, ductal carcinoma: 85%, histological degree 1-2: 59%; stage I-II: 75%, axillary metastasis: 51%, progesterone receptor/estrogen receptors+ (RE/RP+): 78%, HER2+: 10%. Three subtypes were defined: HER2- RE/RP+ (73%), HER2+ (10%) and triple negative (TN) (17%). Subtypes TN and HER2+ were associated with a greater histological degree (GH) (p<0,05) and the TN with lower age at the time of diagnosis than the HER2-, RE/RP+ subtype. Conclusions: the percentage of patients with HER2+ subtype invasive breast cancer (10%) is lower than the one reported in others studies. In accordance with previous studies, TN and HER2+ subtypes correlated with less differentiated tumors and TN subtype occurred in younger patients

Résumé Introduction: le cancer de sein (CS), principal responsable de mort par cancer des uruguayennes, est une maladie hétérogène. L’étude de l’expression tumorale du récepteur du facteur de croissance épidermique 2 (HER-2), le récepteur d’oestrogène (RE) et le récepteur de progestérone (RP) permet de reconnaître des sous-types à caractéristiques cliniques pathologiques et évolutives variées. Objectif: connaître le profil de expression tumorale de HER-2, RE et RP et leur lien avec des données cliniques pathologiques chez des patientes uruguayennes atteintes de cancer de sein. Matériel et méthode: on fait la révision clinique des patientes atteintes de CS ayant subi une intervention chirurgicale pour une période de deux ans, choisissant celles portant la détermination de HER-2, RP et RE par immunohistochimie. On compare le profil de manifestation de ces marqueurs à l’âge au diagnostic, type et degré histologique (GH) et stade pathologique (TNM). Résultats: 197 patientes furent sélectionnées dont voici les caractéristiques: 55 ans (moyenne), 85% carcinome ductal, 59% GH 1-2; 75% stade I- II; 51% métastase axillaire; 78% RE-RP +; 10% HER2+; trois sous-types furent définis: HER2- RE/RP+ (73%), HER2+ (10%) et triple négatif (TN) (17%). Les sous-types TN et HER2+ furent associés à un degré histologique plus grand (p<0,05) et le TN à un âge plus bas au diagnostic (p<0,05) que le sous-type HER2-, RE/RP+. Conclusions: le pourcentage de patientes avec CM invasif sous-type HER2+ (10%) est inférieur à celui reporté par d’autres études (17%-28%). En concordance avec des études préalables, les sous-types TN y HER2+ ont été mis en relation avec des tumeurs plus indifférenciées et le TN a été présent chez des patientes plus jeunes.

Resumo Introdução: o câncer de mama (CM), principal causa de morte por câncer em mulheres uruguaias, é uma doença heterogênea. O estudo da expressão tumoral do receptor do fator de crescimento epidérmico-2 (HER2), do receptor de estrógeno (RE) e do receptor de progesterona (RP) permite reconhecer subtipos com diferentes características clínico-patológicas e de evolução. Objetivos: conhecer o perfil de expressão tumoral de HER2, RE e RP e sua relação com as características clínico-patológicas em pacientes uruguaias com CM. Material e método: os prontuários de pacientes submetidas a cirurgia por CM invasivo em um período de dois anos foram revisados. Foram selecionadas as que incluíam a determinação de RE, RP e HER2 por imuno-histoquímica. O perfil de expressão destes marcadores foi comparado com a idade no momento do diagnóstico, tipo e grau histológico (GH) e estádio patológico (TNM). Resultados: foram selecionadas 197 pacientes cujas características eram idade media: 55 anos, carcinoma ductal: 85%, GH 1-2: 59%, estádio: I-II: 75%, metástases axilares: 51%, RE/RP+: 78%, HER2+: 10%. Foram definidos três subtipos: HER2- RE/RP+ (73%), HER2+ (10%) e triplo negativo (TN) (17%). Os subtipos TN e HER2+ estavam associados a um maior grau histológico (p<0,05) e o TN com menor idade no momento do diagnóstico (p<0,05) que o subtipo HER2-, RE/RP+. Conclusões: a porcentagem de pacientes com CM invasivo subtipo HER2+ (10%) é menor que o informado por outros estudos (17%-28%). No entanto houve concordância com estudos anteriores nos quais os subtipos TN e HER2+ estavam correlacionados com tumores mais indiferenciados e o TN em pacientes más jovens.

Seguimiento en cáncer de colon: ¿cómo y hasta cuándo? / Follow up in colon cancer: how and until when?

Introducción: No existe consenso en la forma en que debe realizarse el seguimiento de los pacientes operados curativamente de cáncer colónico (CC). Es frecuente que el mismo sea exhaustivo, causando innecesaria sobrevigilancia y considerable costo sanitario. El objetivo de este estudio es pautar el seguimiento de los pacientes operados de CC, confeccionando un protocolo basado en la evidencia científica y la experiencia de nuestro grupo de trabajo. Pacientes y Métodos: se analizaron retrospectivamente todos los pacientes operados de CC en el Hospital Central de las Fuerzas Armadas (Uruguay) entre 1988 y 2003. En todos se realizó el seguimiento con: control clínico, CEA, TAC abdomen-pelvis, Rx tórax, ultrasonografia hepática, hemograma, enzimograma hepático. Los eventos de interés fueron: recaída local, a distancia, pólipos, cánceres metacrónicos, fallecimiento. Resultados: En los pacientes con tumores estadio 1 se detectó un único evento (pólipo hiperplásico). En estadios II-III, la mayoría de los eventos se detectaron clínicamente o por elevación CEA, siendo los métodos imagenológicos de escaso aporte. Sólo permitieron la detección más temprana de un 22,7 por ciento de los pacientes con recaída hepática, no pudiendo realizar en la mayoría un tratamiento curativo. Fueron excepcionales los eventos superados los 5 años. Conclusiones: Luego de 5 años de la cirugía proponemos limitar el seguimiento al control clínico y endoscópico cada 3-5 años. En los pacientes con pólipos la frecuencia de la endoscopía debe ajustarse a las características de los mismos. Consideramos innecesaria la realización de estudios imagenológicos durante todo el seguimiento y de CEA una vez superados los 5 años.

Recomendaciones para la prevención y el tratamiento de náuseas y vómitos inducidos por quimioterapia / Nausea and vomiting induced by chemotherapy: prevention and treatment guidelines

Las náuseas y los vómitos son uno de los efectos adversos más frecuentes de la quimioterapia, y uno de los más temidos por los pacientes. El adecuado control de la emesis aguda y tardía redunda en una mejor calidad de vida y una mayor adhesión de los pacientes al tratamiento. A pesar de disponerse actualmente de estrategias antieméticas más efectivas, es frecuente su empleo inadecuado ya sea por sobre o subutilezación. El objetivo de este trabajo es establecer guías precisas para la prevención y el tratamiento de náuseas y vómitos inducidos por quimioterapia, aplicables a nuestro medio, procurando mantener una adecuada relación costo-beneficio. Los factores de riesgo para las náuseas y vómitos inducidos por quimioterapia son dependientes del paciente y del tratamiento, siendo la emetogenicidad propia del plan de quimioterapia el más importante. En las situaciones de alto riesgo de náuseas y vómitos inducidos por quimioterapia (cisplatino, ciclofosfamida, adriamicina, entre otras), la combinación de un antagonista 5HT3 más corticoide previene efectivamente la emesis aguda que otras combinaciones previamente empleadas. En la profilaxis de la emesis tardía no se ha demostrado la superioridad del uso de antagonistas 5HT3 por lo que su mayor costo no justifica su empleo inicial. En las situaciones de riesgo intermedio (5-Fu, taxanos, etopósido) el tratamiento con corticoides o metoclopramida sería suficiente, no recomendándose de inicio profilaxis de la emesis tardía. Para las situaciones de bajo riesgo (bleomicina, vinca) no se sugiere profilaxis de náuseas y vómitos inducidos por quimioterapia. Los antiémeticos vía oral son igualmente efectivos que los intravenosos, por lo que su costo y su conveniencia serían de preferencia.