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INTRODUCTION: Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors in this context. However, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Identifying non-responsive patients early and extending treatment for responsive ones would be ideal, yet optimal strategies are awaited. AIMS: This non-randomized phase 2 clinical trial aims to assess NET feasibility and efficacy in postmenopausal stage II and III luminal BC patients, identifying predictive therapeutic response biomarkers. Efficacy will be gauged by patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) scores 0 post-surgery. Study feasibility will be determined by participation acceptance rate (recruitment rate ≥50%) and inclusion rate (>2 patients/month). METHODS: Postmenopausal women with luminal, HER2-tumors in stages II and III undergo neoadjuvant anastrozole treatment, evaluating continuing NET or receiving chemotherapy through early Ki67 analysis after 2 to 4 weeks. The study assesses NET extension for up to 10 months, using serial follow-ups with standardized breast ultrasound and clinical criteria-based NET suspension. Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.

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Anastrozole, an aromatase inhibitor, induces painful musculoskeletal symptoms, which affect patients' quality of life and lead to therapy discontinuation. Efforts have been made to understand the mechanisms involved in these painful symptoms to manage them better. In this context, we explored the role of the Transient Receptor Potential Vanilloid 4 (TRPV4), a potential transducer of several nociceptive mechanisms, in anastrozole-induced musculoskeletal pain in mice. Besides, we evaluated the possible sensibilization of TRPV4 by signalling pathways downstream, PLC, PKC and PKCε from kinin B2 (B2R) and B1 (B1R) receptors activation in anastrozole-induced pain. Anastrozole caused mechanical allodynia and muscle strength loss in mice. HC067047, TRPV4 antagonist, reduced the anastrozole-induced mechanical allodynia and muscle strength loss. In animals previously treated with anastrozole, the local administration of sub-nociceptive doses of the TRPV4 (4α-PDD or hypotonic solution), B2R (Bradykinin) or B1R (DABk) agonists enhanced the anastrozole-induced pain behaviours. The sensitizing effects induced by local injection of the TRPV4, B2R and B1R agonists in animals previously treated with anastrozole were reduced by pre-treatment with TRPV4 antagonist. Furthermore, inhibition of PLC, PKC or PKCε attenuated the mechanical allodynia and muscle strength loss induced by TRPV4, B2R and B1R agonists. The generation of painful conditions caused by anastrozole depends on direct TRPV4 activation or indirect, e.g., PLC, PKC and PKCε pathways downstream from B2R and B1R activation. Thus, the TRPV4 channels act as sensors of extracellular and intracellular changes, making them potential therapeutic targets for alleviating pain related to aromatase inhibitors use, such as anastrozole.

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Objective: This research aimed to evaluate retrospectively the effect of anastrozole on height gain and sex hormone levels in pubertal boys receiving growth hormone (GH). Materials and methods: Pubertal boys who received both GH and anastrozole (GH+A) were one-to-one matched with boys who received only GH (GH-Only) for chronological and bone age, pubertal stage and height before the GH initiation, treatment duration and midparental height. Anthropometric measurements throughout treatment and adult heights were compared between the groups. Sex hormone levels were evaluated longitudinally in the GH+A group. Results: Forty-eight cases (24 in each group) were included. There was no statistical difference in adult height between the GH+A and GH-Only (p = 0.071). However, when the analysis was limited to those receiving anastrozole for at least 2 years, mean adult height was higher in the GH+A than in the GH-Only group (173.1 ± 6.2/169.8 ± 5.6 cm, p = 0.044). Despite similar growth rates between the two groups, bone age advancement was slower in the GH+A than in the GH-Only in a mean anastrozole treatment period of 1.59 years (1.37 ± 0.80/1.81 ± 0.98 years, p = 0.001). The greatest increase for FSH, LH, total and free testosterone and decrease for estradiol levels were observed in the third month after anastrozole was started, albeit remaining within the normal ranges according to the actual pubertal stages. Conclusion: Using anastrozole with GH for at least 2 years decelerates the bone age advancement resulting in adult height gain with no abnormality in sex hormone levels. These results suggest anastrozole can be used as an additional treatment to GH for further height gain in pubertal boys.

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PURPOSE: Self-administered oncology drugs contribute disproportionately to Medicare Part D spending; prices often remain high even after generic entry. Outlets for low-cost drugs such as Mark Cuban Cost Plus Drug Company (MCCPDC) offer opportunities for decreased Medicare, Part D, and beneficiary spending. We estimate potential savings if Part D plans obtained prices such as those offered under the MCCPDC for seven generic oncology drugs. METHODS: Using the 2020 Medicare Part D Spending dashboard, Q3-2022 Part D formulary prices, and Q3-2022 MCCPDC prices for seven self-administered generic oncology drugs, we estimated Medicare savings by replacing Q3-2022 Part D unit costs with costs under the MCCPDC plan. RESULTS: We estimate potential savings of $661.8 million (M) US dollars (USD; 78.8%) for the seven oncology drugs studied. Total savings ranged from $228.1M USD (56.1%) to $2,154.5M USD (92.4%) compared with 25th and 75th percentiles of Part D plan unit prices. The median savings replacing Part D plan prices were abiraterone $338.0M USD, anastrozole $1.2M USD, imatinib 100 mg $15.6M USD, imatinib 400 mg $212.0M USD, letrozole $1.9M USD, methotrexate $26.7M USD, raloxifene $63.8M USD, and tamoxifen $2.6M USD. All 30-day prescription drug prices offered by MCCPDC generated cost savings except for three drugs offered at the 25th percentile Part D formulary pricing: anastrozole, letrozole, and tamoxifen. CONCLUSION: Replacing current Part D median formulary prices with MCCPDC pricing could yield significant savings for seven generic oncology drugs. Individual beneficiaries could save nearly $25,200 USD per year for abiraterone or between $17,500 USD and $20,500 USD for imatinib. Notably, Part D cash-pay prices for abiraterone and imatinib under the catastrophic phase of coverage were still more expensive than baseline MCCPDC prices.

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OBJECTIVE: To map the evidence available in the literature on the health-related quality of life of women with breast cancer using hormone therapy. DATA SOURCES: This review followed the Joanna Briggs Institute methodological recommendations and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. Searches were performed in nine databases using descriptors, synonyms and keywords; grey literature was also included. The review protocol was registered with the Open Science Framework under doi: http://doi.org/10.17605/OSF.IO/347FM. Inclusion criteria were established according to the Population, Concept, and Context strategy. The selection of studies was performed by two independent reviewers with the aid of RAYYAN software and disagreements were resolved by a third reviewer. The main information from the included articles was grouped into textual categories and presented by means of a narrative synthesis. DATA SUMMARY: A total of 5419 records were identified, of which 42 studies fully met the eligibility criteria. Most were multicenter studies (42.9%) and randomized controlled trials (62%). Most studies addressed anastrozole (39.5%), letrozole (34.2%), and tamoxifen (26.3%), which were studied alone or in combination. The most widely used health-related quality-of-life assessment tool was the EORTC-QLQ-C30. The concomitant use of hormone therapy and cyclin-dependent kinase inhibitors 4 and 6 showed improvement in health-related quality of life. CONCLUSION: In recent years there has been an increase in studies focused on health-related quality of life, and the evidence pointed to relevant information on health-related quality of life and the use of endocrine therapy, tamoxifen in combination with aromatase inhibitors, as well as aromatase inhibitor alone and the use of cyclin-dependent kinase 4 and 6.

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ANTECEDENTES: El presente dictamen preliminar expone la evaluación de la eficacia y seguridad de fulvestrant (monoterapia), en comparación con la quimioterapia, en el tratamiento de pacientes posmenopáusicas con cáncer de mama metastásico (CMM), receptor hormonal (RH) positivo, receptor 2 del factor de crecimiento epidérmico humano (HER2, por sus siglas en inglés) negativo, sin crisis visceral, con intolerancia o progresión a anastrozol y exemestano. SPECTOS GENERALES Los aspectos generales del cáncer de mama se han descrito previamente en los Dictámenes Preliminares N.° 022-DETS-IETSI-2021 (IETSI-EsSalud 2021a), N° 008- DETS-IETSI-2021 (IETSI-EsSalud 2021b) y N° 050-SDEPFyOTS-DETS-IETSI-2016 (IETSI-EsSalud 2016). Brevemente, el cáncer de mama es la primera causa de muerte por neoplasia maligna en mujeres en el mundo (Institute for Health Metrics and Evaluation 2021). En el 2019, en Perú se detectaron 4,743 casos nuevos de cáncer de mama en mujeres, y cerca de 1,840 muertes debido a esta condición clínica (Institute for Health Metrics and Evaluation 2021). El cáncer de mama con RH positivo es el tipo más común de cáncer de mama, y representa el 75 % de todos los cánceres de mama (Pritchard 2021). El tratamiento de elección del cáncer de mama con RH positivo es la terapia endocrina (Pritchard 2021; National Cancer Institute 2021). Específicamente, en las mujeres posmenopáusicas con CMM, RH positivo, HER2 negativo, la terapia endocrina de primera línea más utilizada son los IA, como el agente no esteroideo anastrozol y el agente esteroideo exemestano (National Cancer Institute 2021). Muchos de estos pacientes eventualmente presentan intolerancia o enfermedad progresiva durante la terapia endocrina con IA. En este contexto, las opciones de tratamiento son limitadas, e incluyen el uso de la quimioterapia (National Cancer Institute 2021; Ma and Sparano 2021). TECNOLOGÍA SANITARIA DE INTERÉS: FULVESTRANT: La información detallada sobre esta tecnología sanitaria se encuentra disponible en los Dictámenes Preliminares N.° 022-DETS-IETSI-2021 (IETSI-EsSalud 2021a) y N.° 050- SDEPFyOTS-DETS-IETSI-2016 (IETSI-EsSalud 2016). El fulvestrant es un antagonista competitivo del receptor del estrógeno que bloquea las acciones tróficas de los estrógenos sin poseer actividad agonista parcial (de tipo estrógeno). El mecanismo de acción está asociado con la regulación a la baja de los niveles de la proteína del receptor de estrógeno (U.S. Food and Drug Administration 2021; European Medicines Agency 2021). METODOLOGÍA: Se realizó una búsqueda sistemática de literatura con el objetivo de identificar evidencia sobre la eficacia y seguridad de fulvestrant (monoterapia) en comparación con la quimioterapia en pacientes posmenopáusicas con CMM, RH positivo, HER2 negativo, sin crisis visceral, con intolerancia o progresión durante la terapia endocrina con anastrozol y exemestano. Se utilizaron las bases de datos PubMed, Cochrane Library y LILACS. Asimismo, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), incluyendo el Scottish Medicines Consortium (SMC), el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institut für Qualitát und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), el Instituto de Evaluación Tecnológica en Salud de Colombia (IETS), la Comissáo Nacional de Incorpornáo de Tecnologias no Sistema Único de Saúde (CONITEC), entre otros; además de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en el manejo del cáncer de mama como National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) y American Society of Clinical Oncology (ASCO). Se hizo una búsqueda adicional en la página web del registro de ensayos clínicos administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.qov/)e International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/), para poder identificar ensayos clínicos en curso o cuyos resultados no hayan sido publicados para, de este modo, disminuir el riesgo de sesgo de publicación. RESULTADOS: Guías de práctica clínica Publicaciones incluidas en la evaluación de la evidencia: Cardoso et al., 2020. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5) (Cardoso et al. 2020). National Comprehensive Cancer Network (NCCN). NCCN Guidelines: Breast Cancer. Version 8.2021 - September 13, 2021 (NCCN 2021). Moy et al., 2021. Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2­Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor­Negative: ASCO Guideline Update (Moy et al. 2021). El siguiente documento se excluyó por tratarse de un consenso de expertos. Pritchard et al., 2013. Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: A Canadian consensus statement (Pritchard et al. 2013). CONCLUSIONES: El objetivo del presente dictamen preliminar fue evaluar la mejor evidencia científica sobre la eficacia y seguridad de fulvestrant (monoterapia) en comparación con la quimioterapia en pacientes posmenopáusicas con CMM, RH positivo, HER2 negativo, sin crisis visceral, con intolerancia o progresión durante la terapia endocrina con anastrozol y exemestano. La búsqueda de literatura permitió identificar tres GPC realizadas por la ESMO, la NCCN y la ASCO. En cuanto a las GPC identificadas, hubo discordancia entre las recomendaciones elaboradas para el tratamiento de mujeres posmenopáusicas con CMM, RH positivo, HER2 negativo, sin crisis visceral, con progresión durante la terapia endocrina. La NCCN recomienda el uso de la terapia endocrina, incluido fulvestrant, en el subgrupo de pacientes sin resistencia a la terapia endocrina, y la quimioterapia en el subgrupo con resistencia a la terapia endocrina. La ESMO recomienda el uso de la terapia endocrina, incluido fulvestrant, en la población objetivo, y no elabora recomendaciones sobre la quimioterapia. La ASCO recomienda el uso de la terapia endocrina con o sin terapia dirigida y la quimioterapia de un solo agente, sin preferencias entre una u otra. Sobre la evidencia utilizada para realizar las recomendaciones, la ESMO no citó evidencia alguna, mientras que la NCCN y la ASCO citaron evidencia que no respondía a la pregunta PICO establecida en el presente dictamen. En el momento actual no hay evidencia que compare la terapia endocrina con fulvestrant (monoterapia) versus la quimioterapia en mujeres posmenopáusicas con CMM, RH positivo, HER2 negativo, con intolerancia o progresión durante la terapia endocrina. En ese sentido, existe incertidumbre sobre el beneficio adicional del uso de fulvestrant sobre la quimioterapia en la población objetivo. La quimioterapia de agente único es una opción de tratamiento recomendada por la guía de la ASCO para la población objetivo de la presente evaluación. En EsSalud, hay varias opciones de quimioterapia disponibles en la Petitorio Farmacológico y existe una amplia experiencia en el uso de la quimioterapia en el tratamiento del CMM. Por lo expuesto, el IETSI no aprueba el uso de fulvestrant en pacientes posmenopáusicas con CMM, RH positivo, HER2 negativo, sin crisis visceral, con intolerancia o progresión durante la terapia endocrina con anastrozol y exemestano.

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Introdução: Entre os cânceres de mama, aproximadamente 75% das mulheres são receptores hormonais positivos, sendo estas mais propensas a responderem à hormonioterapia com anastrozol e tamoxifeno. Apesar de eficazes, apresentam taxas significativas de não adesão. Objetivo: Avaliar a adesão à terapia hormonal adjuvante com tamoxifeno e anastrozol em pacientes atendidos nos Ambulatórios da Mastologia e de Quimioterapia do Hospital São Paulo entre os anos de 2019 e 2020. Método: Estudo transversal com 102 mulheres, realizado entre os meses de setembro de 2019 e março de 2020. A adesão à terapia hormonal adjuvante foi avaliada utilizando-se as escalas Morisky Medication Adherence Scale (MMAS-4) e Adherence to Refills and Medications Scale of 12 items (ARMS-12). Resultados: A média de idade foi de 61,5 anos (59,3-63,6). Entre as pacientes, 27,7% faziam uso de tamoxifeno e 72,3% de anastrozol. Relataram desconforto em relação ao uso do medicamento 84,4%, sendo as ondas de calor (42,2%) e as dores articulares (55,9%) os mais frequentes. A escala de ARMS>12 foi pontuada por 79,2%; cerca de 90% das mulheres pontuaram a MMAS-4 até dois pontos, porém não houve diferença significativa entre os tipos de hormônios utilizados para escalas de adesão (p=0,815 e p=0,489). Conclusão: A adesão à hormonioterapia observada foi relativamente baixa, independentemente da endocrinoterapia, podendo essas pacientes estarem em risco de inadequação quanto à resposta clínica

Introduction: Among breast cancers, approximately 75% of women are hormone receptors-positive, and these are more likely to respond to hormone therapy with anastrozole and tamoxifen. Although effective, they have significant rates of non-adherence. Objective: To evaluate adherence to adjuvant hormone therapy with tamoxifen and anastrozole in patients consulted at the Mastology and Chemotherapy Outpatient Clinic of Hospital São Paulo between 2019 and 2020. Method: Cross-sectional study carried out with 102 women between September 2019 and March 2020. Adherence to hormone therapy was evaluated using the Morisky Medication Adherence Scale (MMAS-4) and Adherence to Refills and Medications Scale of 12 items (ARMS-12). Results: The mean age was 61.5 years (59.3-63.6). Among the patients, 27.7% used tamoxifen and 72.3%, anastrozole. 84.4% of them reported discomfort in using the medication, the most frequent were hot flashes (42.2%) and joint pain (55.9%). 79.2% scored the ARMS>12 scale, about 90% of the women scored MMAS-4 up to 2 points, but there was no significant difference between the types of hormones used for adhesion scales (p=0.815 to p=0.489). Conclusion: Adherence to hormone therapy was relatively low, regardless of the hormone used, and these patients may be at risk of inadequate clinical response

Introducción: Entre los cánceres de mama, aproximadamente el 75% de las mujeres son receptores hormonales positivos, y estas son más propensas a responder a la terapia hormonal con anastrozol y tamoxifeno. Aunque son eficaces, tienen tasas significativas de no adherencia. Objetivo: Evaluar la adhesión a la terapia hormonal adyuvante con tamoxifeno y anastrozol en pacientes atendidas en las Clínicas Ambulatorias de Mastología y Quimioterapia del Hospital São Paulo entre 2019 y 2020. Método: Este es un estudio transversal realizado con 102 mujeres entre septiembre de 2019 y marzo de 2020. La terapia hormonal adjunta se evaluó utilizando las escalas Morisky Medication Adherence Scale (MMAS-4) e Adherence to Refills and Medications Scale of 12 items (ARMS-12). Resultados: La edad media fue de 61,5 años (59,3-63,6). Entre las pacientes, el 27,7% utilizaron tamoxifeno y el 72,3% anastrozol. El 84,4% de ellas reportaron molestias en relación con el uso del medicamento, siendo los más frecuentes los sofocos (42,2%) y el dolor articular (55,9%). 79,2% puntuaron la escala ARMS>12, alrededor del 90% de las mujeres obtuvieron MMAS-4 hasta dos puntos, pero no hubo diferencia significativa entre los tipos de hormonas utilizadas para escalas de adhesión (p=0,815 a p=0,489). Conclusión: La adherencia de la terapia hormonal observada fue relativamente baja, independientemente de la hormona utilizada, y estas mujeres pueden estar en riesgo de respuesta clínica inadecuada

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Occult breast cancer (OBC) is characterized by metastatic presentation of undetectable breast tumor on imaging exams. OBC is a rare disease (accounting for 0.3% to 1.0% of all breast cancers) that represents a major diagnostic challenge. The aim of this study was to report a case of OBC with primary presentation of multiple cutaneous metastases with subsequent emergence of bone metastasis. A 70-year female patient had multiple cutaneous metastatic lesions in the left cervical region, left breast, left axillary region, left subscapular region, in three chirodactylus of the right hand and three chirodactylus of the left hand. Imaging tests (mammogram, ultrasonography and magnetic resonance imaging of the breast) did not show alterations. Biopsy, histology sections and immunohistochemistry of the left cervical cutaneous lesion were compatible with OBC. After two years of anastrozole treatment (1mg/day), there was regression of all cutaneous lesions and stabilization of bone metastasis. OBC has a better prognosis. It may exhibit spontaneous regression or respond to less aggressive treatment strategies, as described in this case.

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Abstract Objective The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer. Methods This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017. Results From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, 'disease progression' was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, 'presence of side effects' was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities. Conclusion The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.

Resumo Objetivo O objetivo do presente estudo foi analisar os motivos que levaram às mudanças no esquema hormonioterápico (HT) em mulheres com câncer de mama. Métodos Estudo transversal retrospectivo realizado no Hospital da Mulher de Campinas e consequente pesquisa de prontuários de mulheres diagnosticados com câncer de mama entre janeiro de 2012 e janeiro de 2017. Resultados De 1.555 mulheres em tratamento com HT, 213 (13,7%) mulheres tiveram HT alterado, tamoxifeno para anastrozol ou vice-versa. A maioria das mulheres incluídas no presente estudo que tiveram mudança de HT tinha > 50 anos, estava na pós-menopausa, era caucasiana e tinha pelo menos uma comorbidade. Os principais motivos de troca de HT foram devido a 'progressão da doença', ocorrendo em 124 (58,2%) casos e a 'presença de efeitos colaterais' (n = 65; 30,5%). Das mulheres que sofreram efeitos colaterais, 24 (36,9%) apresentaram comorbidades. Conclusão O presente estudo demonstrou uma baixa taxa na alteração de tamoxifeno para anastrozol. Entre as razõesmais comuns para alterar a HT estava a progressão da doença, que inclui recorrência do câncer, metástase ou aumento do tumor. Os efeitos colaterais foram a segunda causa e, além disso, a idade e as comorbidades foram fatores de risco para efeitos colaterais.

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INTRODUCCIÓN: El presente dictamen preliminar expone la evaluación de la eficacia y seguridad de ribociclib más fulvestrant, en comparación con exemestano o anastrozol, en mujeres posmenopáusicas con cáncer de mama metastásico, RH-positivo y HER2-negativo, sin tratamiento previo o con una línea previa de terapia endocrina para enfermedad metastásica. El cáncer de mama es la primera causa de muerte por neoplasia maligna en mujeres en el mundo. En el 2019, en Perú se detectaron 4,743 casos nuevos de cáncer de mama en mujeres; causando cerca de 1,840 muertes en el mismo año. El cáncer de mama metastásico (CMM) es una condición incurable. Se estima que la mediana de sobrevida global en pacientes con CMM es de aproximadamente tres años y que la tasa de sobrevida global hasta los 5 años es de aproximadamente 27%. Los tipos de medicamentos que se usan para el CMM dependen del estado menopáusico de la paciente, del estado del receptor hormonal (RH) y del receptor 2 del factor de crecimiento epidérmico humano (HER2) del cáncer. En el contexto de EsSalud, las mujeres posmenopáusicas con CMM, RH-positivo, HER2-negativo, sin tratamiento previo o con una línea previa de terapia endocrina para enfermedad metastásica, a menudo se tratan con un inhibidor de la aromatasa (anastrozol o exemestano). El IETSI-EsSalud recibió una solicitud de evaluación de ribociclib más fulvestrant como una alternativa terapéutica al uso de inhibidores de la aromatasa, argumentándose una potencial prolongación de la sobrevida global de los pacientes, junto con un perfil de seguridad aceptable. Al respecto, el IETSI-EsSalud consideró que existe la necesidad de terapias nuevas y efectivas para los pacientes con CMM que proporcionen mejoras en la sobrevida global del paciente, tengan perfiles de toxicidad más favorables y mejoren la calidad de vida. METODOLOGÍA: Se realizó una búsqueda sistemática de literatura con el objetivo de identificar evidencia sobre la eficacia y seguridad de ribociclib más fulvestrant, en comparación con exemestano o anastrozol, en mujeres posmenopáusicas con CMM, RH-positivo y HER2-negativo, sin tratamiento previo o con una línea previa de terapia endocrina para enfermedad metastásica. Se utilizaron las bases de datos PubMed, Cochrane Library y LILACS, priorizándose la evidencia proveniente de ensayos clínicos controlados aleatorizados. Asimismo, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan ETS y GPC, incluyendo el Healthcare Improvement Scotland, el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), además de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en el manejo del cáncer de mama como National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) y American Society of Clinical Oncology (ASCO). Se hizo una búsqueda adicional en la página web del registro de ensayos clínicos administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.gov/) e International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/), para poder identificar ensayos clínicos en curso o cuyos resultados no hayan sido publicados para, de este modo, disminuir el riesgo de sesgo de publicación. RESULTADOS: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de ribociclib más fulvestrant, en comparación con exemestano o anastrozol, en mujeres posmenopáusicas con CMM, RH-positivo y HER2-negativo, sin tratamiento previo o con una línea previa de terapia endocrina para enfermedad metastásica. CONCLUSIONES: El presente dictamen preliminar tuvo como objetivo evaluar la mejor evidencia sobre la eficacia y seguridad sobre la eficacia y seguridad de ribociclib más fulvestrant, en comparación con anastrozol y exemestano, en mujeres posmenopáusicas con CMM, RH-positivo y HER2-negativo, sin tratamiento previo o con una línea previa de terapia endocrina para enfermedad metastásica. La evidencia clave para evaluar el uso de ribociclib en combinación con fulvestrant en la población de interés proviene de MONALEESA-3, un ECA de fase III, doble ciego, controlado con placebo, de grupos paralelos. El estudio MONALEESA-3 tuvo la limitación de no responder directamente a la pregunta PICO de interés, ya que evaluó el uso de ribociclib más fulvestrant en comparación con fulvestrant solo, y no versus el comparador de interés del presente dictamen (anastrozol o exemestano). Cabe señalar que el uso de fulvestrant como monoterapia no está aprobado en EsSalud porque no se ha demostrado que sea diferente del exemestano, en términos de calidad de vida y eventos adversos en pacientes posmenopáusicas con CMM, RH-positivo y tratamiento endocrino previo, y no hay evidencia que permita generar conclusiones definitivas respecto a la sobrevida global (Dictamen Preliminar de Evaluación de Tecnología Sanitaria N.° 050-SDEPFyOTS-DETS-IETSI-2016). Los resultados de MONALESSA-3 no permiten determinar un beneficio neto con ribociclib más fulvestrant en comparación con fulvestrant más placebo por las siguientes razones: i) los resultados disponibles de SG son aún preliminares (corresponden a análisis interinos) y requieren de un mayor seguimiento (resultados del análisis final de SG) para determinar si realmente existe un beneficio en la prolongación de la vida de los pacientes, más aun en vista de una modesta reducción en el riesgo de mortalidad y una gran incertidumbre en las estimaciones reportadas (amplio intervalo de confianza, con valores cercanos al valor de la no diferencia), ii) los resultados muestran que ribociclib más fulvestrant no mejora la calidad de vida de los pacientes y, iii) los resultados muestran que ribociclib más fulvestrant aumenta significativamente el riesgo de EA serios y discontinuación debido a EA asociados a la medicación. Debido a la incertidumbre en la relación de riesgo-beneficio con ribociclib más fulvestrant, en comparación con anastrozol y/o exemestano, dada principalmente por la ausencia de evidencia que responda directamente a la pregunta PICO establecida en el presente dictamen, la aprobación de uso de ribociclib más fulvestrant no sería una decisión costo-oportuna; dada la disponibilidad de tratamientos efectivos, con perfiles de seguridad aceptables y menos costosos en la institución (anastrozol y exemestano), los cuales son recomendados en las GPC internacionales más recientes para la población de interés del presente dictamen. Por lo expuesto, el IETSI no aprueba el uso de ribociclib más fulvestrant en mujeres posmenopáusicas con CMM, RH-positivo y HER2-negativo, sin tratamiento previo o con una línea previa de terapia endocrina para enfermedad metastásica.

RESUMO

OBJECTIVE: The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer. METHODS: This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017. RESULTS: From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, 'disease progression' was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, 'presence of side effects' was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities. CONCLUSION: The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.

OBJETIVO: O objetivo do presente estudo foi analisar os motivos que levaram às mudanças no esquema hormonioterápico (HT) em mulheres com câncer de mama. MéTODOS: Estudo transversal retrospectivo realizado no Hospital da Mulher de Campinas e consequente pesquisa de prontuários de mulheres diagnosticados com câncer de mama entre janeiro de 2012 e janeiro de 2017. RESULTADOS: De 1.555 mulheres em tratamento com HT, 213 (13,7%) mulheres tiveram HT alterado, tamoxifeno para anastrozol ou vice-versa. A maioria das mulheres incluídas no presente estudo que tiveram mudança de HT tinha > 50 anos, estava na pós-menopausa, era caucasiana e tinha pelo menos uma comorbidade. Os principais motivos de troca de HT foram devido a 'progressão da doença', ocorrendo em 124 (58,2%) casos e a 'presença de efeitos colaterais' (n = 65; 30,5%). Das mulheres que sofreram efeitos colaterais, 24 (36,9%) apresentaram comorbidades. CONCLUSãO: O presente estudo demonstrou uma baixa taxa na alteração de tamoxifeno para anastrozol. Entre as razões mais comuns para alterar a HT estava a progressão da doença, que inclui recorrência do câncer, metástase ou aumento do tumor. Os efeitos colaterais foram a segunda causa e, além disso, a idade e as comorbidades foram fatores de risco para efeitos colaterais.

RESUMO

Anastrozole (ANZ) is a breast cancer drug that was introduced onto the pharmaceutical market in the 1990s and is still one of the most widely consumed cytotoxic compounds. Due to the persistence of the drug, its continued presence after passing through wastewater treatment plants can lead to harm to aquatic environments. The present study investigates use of the solar photo-Fenton (SPF) process applied for ANZ degradation, considering the fate of ANZ and its transformation products (TPs). The SPF process was performed using different concentrations of ferrous iron (Fe2+) and H2O2 in solutions produced with deionized water (DW) and hospital wastewater (HWW), at pH close to neutrality. When solar irradiation in the SPF process was carried out the best ANZ removal rates were found under the following conditions: (i) for the DW matrix, [ANZ]0 = 50 µg L-1, [Fe2+] = 5 mg L-1, and [H2O2]0 = 25 mg L-1, achieving 95% primary ANZ elimination; (ii) for the HWW matrix, [ANZ]0 = 50 µg L-1, [Fe2+] = 10 mg L-1(multiple additions), and [H2O2]0 = 25 mg L-1, achieving 51% primary ANZ elimination. LC-QTOF MS analysis allowed to identify tentatively five transformation products (TPs) formed during the ANZ degradation process in DW, and two TPs when HWW was used. The main proposed degradation pathways were demethylation and hydroxylation. Different in silico models free available (quantitative) structure-activity relationship ((Q)SAR) software were used to predict the ecotoxicities and environmental fates of ANZ and the TPs. The in silico (Q)SAR predictions indicated that ANZ and the TPs were non-biodegradable compounds. In silico (Q)SAR predictions for mutagenicity and carcinogenicity end-points identified some TPs that require further study. Attention is drawn to the formation of several TPs for which statistical and rule-based positive alerts for mutagenic activities were found, requiring further confirmatory in vitro validation tests.

RESUMO

OBJECTIVE: The objective of the present study is to observe the frequency and severity of urinary symptoms in women with breast cancer (BC) being treated with oral hormone therapy, associating them to drug adherence. METHODS: The participants were interviewed once from June to October 2016. The evaluation of urinary symptoms was performed by two questionnaires: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB). Adherence was evaluated by the Morisky-Green method. Statistical analysis was performed by the Mann-Whitney test, linear regression, and Spearman correlation. RESULTS: Fifty-eight women were interviewed: 42 treated with tamoxifen and 16 with aromatase inhibitor. Twenty-seven women (46.5%) presented urinary incontinence symptoms and 15 (25.8%) presented stress urinary incontinence (SUI). Fourteen (24.1%) women had symptoms of overactive bladder (OAB). There was no statistical difference in symptoms between both treatments and duration of treatments. Higher scores in the ICIQ-SF questionnaire were associated with low/medium adherence and advanced age. Higher scores in the ICIQ-OAB questionnaire were associated with low/medium adherence. CONCLUSION: The present study showed a high prevalence of urinary symptoms, such as urinary incontinence and OAB, associated with low/medium adherence and older age in women with BC being treated with oral hormone therapy. Health professionals should be alert to these symptoms since it could influence life quality and adherence to treatment.

OBJETIVO: O objetivo do presente estudo foi observar a frequência e a gravidade dos sintomas urinários em mulheres com câncer de mama em uso de terapia hormonal oral, associando estes com a adesão ao tratamento. MéTODOS: As pacientes foram entrevistadas uma única vez, entre junho e outubro de 2016. A avaliação dos sintomas urinários foi realizada por dois questionários: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF, na sigla em inglês) e o Questionário Sobre Bexiga Hiperativa (ICIQ-OAB, na sigla em inglês). A adesão foi avaliada pelo método Morisky-Green. A análise estatística foi realizada pelo teste de Mann-Whitney, regressão linear e correlação de Spearman. RESULTADOS: Foram entrevistadas 58 mulheres: 42 tratadas com tamoxifeno e 16 com inibidor de aromatase. Vinte e sete mulheres (46,5%) apresentaram sintomas de incontinência urinária (IU) e 15 (25,8%) apresentaram incontinência urinária por estresse (IUS). Quatorze (24,1%) das mulheres tinham sintomas de bexiga hiperativa. Não houve diferença estatística nos sintomas entre os tratamentos e a duração dos tratamentos. Os escores mais elevados no questionário ICIQ-SF estiveram associados à baixa/média adesão e à idade avançada. Os escores mais elevados no questionário da ICIQ-OAB foram associados à baixa/média adesão. CONCLUSãO: O presente estudo mostrou alta prevalência de sintomas urinários, como IU e bexiga hiperativa, associadas à baixa/média adesão e à idade mais avançada em mulheres com câncer de mama em tratamento com hormonioterapia oral. Os profissionais de saúde devem estar atentos a esses sintomas, pois eles podem influenciar a qualidade de vida e a adesão ao tratamento.

RESUMO

Abstract Objective: The objective of the present study is to observe the frequency and severity of urinary symptoms in women with breast cancer (BC) being treated with oral hormone therapy, associating them to drug adherence. Methods: The participants were interviewed once from June to October 2016. The evaluation of urinary symptoms was performed by two questionnaires: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB). Adherence was evaluated by the Morisky-Green method. Statistical analysis was performed by the Mann-Whitney test, linear regression, and Spearman correlation. Results: Fifty-eight women were interviewed: 42 treated with tamoxifen and 16 with aromatase inhibitor. Twenty-seven women (46.5%) presented urinary incontinence symptoms and 15 (25.8%) presented stress urinary incontinence (SUI). Fourteen (24.1%) women had symptoms of overactive bladder (OAB). There was no statistical difference in symptoms between both treatments and duration of treatments. Higher scores in the ICIQ-SF questionnaire were associated with low/medium adherence and advanced age. Higher scores in the ICIQ-OAB questionnaire were associated with low/medium adherence. Conclusion: The present study showed a high prevalence of urinary symptoms, such as urinary incontinence and OAB, associated with low/medium adherence and older age in women with BC being treated with oral hormone therapy. Health professionals should be alert to these symptoms since it could influence life quality and adherence to treatment.

Resumo Objetivo: O objetivo do presente estudo foi observar a frequência e a gravidade dos sintomas urinários em mulheres com câncer de mama em uso de terapia hormonal oral, associando estes com a adesão ao tratamento. Métodos: As pacientes foram entrevistadas uma única vez, entre junho e outubro de 2016. A avaliação dos sintomas urinários foi realizada por dois questionários: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF, na sigla em inglês) e o Questionário Sobre Bexiga Hiperativa (ICIQ-OAB, na sigla em inglês). A adesão foi avaliada pelo método Morisky-Green. A análise estatística foi realizada pelo teste de Mann-Whitney, regressão linear e correlação de Spearman. Resultados: Foram entrevistadas 58 mulheres: 42 tratadas com tamoxifeno e 16 com inibidor de aromatase. Vinte e sete mulheres (46,5%) apresentaram sintomas de incontinência urinária (IU) e 15 (25,8%) apresentaram incontinência urinária por estresse (IUS). Quatorze (24,1%) das mulheres tinham sintomas de bexiga hiperativa. Não houve diferença estatística nos sintomas entre os tratamentos e a duração dos tratamentos. Os escores mais elevados no questionário ICIQ-SF estiveram associados à baixa/média adesão e à idade avançada. Os escores mais elevados no questionário da ICIQ-OAB foram associados à baixa/média adesão. Conclusão: O presente estudo mostrou alta prevalência de sintomas urinários, como IU e bexiga hiperativa, associadas à baixa/média adesão e à idade mais avançada em mulheres com câncer de mama em tratamento com hormonioterapia oral. Os profissionais de saúde devem estar atentos a esses sintomas, pois eles podem influenciar a qualidade de vida e a adesão ao tratamento.

RESUMO

OBJECTIVES: Aromatase inhibitors are the first-choice drugs for the treatment of hormone sensitive breast cancer. However, in addition to the scarcity of studies, there are controversies about their effects on vaginal epithelial cell proliferation in rats, especially those in persistent estrus. METHODS: To investigate vaginal epithelial cell proliferation by Ki-67 antigen expression, persistent estrus was induced in 42 randomly selected rats. These rats were randomly divided into 2 groups: group I (control, n=21), which received 0.1 mL of propylene glycol (vehicle) daily, and group II (experimental, n=21), which received 0.5 mg/kg or 0.125 mg/day of anastrozole diluted with 0.1 mL of propylene glycol. RESULTS: Light microscopy showed a higher concentration of cells with brown Ki-67 stained nuclei in the control compared to the experimental group. The mean percentage of Ki-67 stained nuclei per 500 cells in the vaginal epithelium was 68.64±2.64 and 30.46±2.00 [mean±standard error of the mean (SEM)] in the control and experimental groups, respectively (p<0.003). CONCLUSION: This study showed that anastrozole, at the dose and treatment duration selected, significantly decreased cell proliferation in the vaginal mucosa of the rats in persistent estrus.

RESUMO

An alternative hyper-ovulator inducer to replace clomiphene citrate (CC) is needed as it is unsuitable for women with polycystic ovarian syndrome and is associated with low pregnancy rates. Anastrozole is an effective hyper-ovulator inducer, but has not been well researched. In order to determine the effectiveness of anastrozole as a hyper-ovulator inducer and to an extent compare it with CC in similar situations, this study ascertained the effects of these drugs on the expression of the focal adhesion proteins, paxillin and FAK, which are uterine receptivity markers in the surface luminal uterine epithelial cells of day 1 and day 6 pregnant Wistar rats. The results show that paxillin is localized in focal adhesions at the base of the uterine epithelial cells at day 1 of pregnancy whereas at day 6, paxillin disassembles from the basal focal adhesions and localizes and increases its expression apically. FAK is faintly expressed at the basal aspect of the uterine epithelial cells while moderately expressed at the cell-to-cell contact at day 1 in all groups from where it disassembles and relocates apically and becomes more intensely expressed at day 6 of pregnancy in untreated and anastrozole treated rats. Although paxillin is localized apically at day 6, its expression is significantly down-regulated with CC treatment suggesting its interference with the implantation process. These findings seem to suggest that anastrozole could favor implantation.

Para reemplazar el citrato de clomifeno (CC) es necesario un inductor de hiperovulación alternativo, ya que no es adecuado para mujeres con síndrome de ovario poliquístico y está asociado con tasas bajas de embarazo. El anastrozol es un inductor eficaz del hiper-ovulador, pero no se ha investigado adecuadamente. Con el fin de determinar la efectividad del anastrozol como inductor del hiper-ovulador y, en cierta medida, compararlo con CC en situaciones similares, este estudio determinó los efectos de estos fármacos en la expresión de las proteínas de adhesión focal, paxillin y FAK, uterinas marcadores de receptividad en la superficie luminal de células uterinas epiteliales, del día 1 y día 6 en ratas Wistar preñadas. Los resultados muestran que la paxilina se localiza en adherencias focales en la base de las células epiteliales uterinas en el día 1 del embarazo, mientras que en el día 6, la paxilina se desmonta de las adherencias focales basales y localiza y aumenta su expresión apicalmente. FAK se expresa débilmente en el aspecto basal de las células epiteliales uterinas, mientras que se expresa moderadamente en el contacto de célula a célula en el día 1 en todos los grupos, donde se separa y se reubica apicalmente y se expresa con mayor intensidad el día 6 de la preñez, en pacientes no tratados y tratados. ratas tratadas con anastrozol. Aunque la paxillina se localiza apicalmente en el día 6, su expresión está significativamente disminuida con el tratamiento con CC, lo que sugiere su interferencia con el proceso de implantación. Estos hallazgos sugieren que el anastrozol podría favorecer el proceso de implantación.

RESUMO

OBJECTIVES: Aromatase inhibitors are the first-choice drugs for the treatment of hormone sensitive breast cancer. However, in addition to the scarcity of studies, there are controversies about their effects on vaginal epithelial cell proliferation in rats, especially those in persistent estrus. METHODS: To investigate vaginal epithelial cell proliferation by Ki-67 antigen expression, persistent estrus was induced in 42 randomly selected rats. These rats were randomly divided into 2 groups: group I (control, n=21), which received 0.1 mL of propylene glycol (vehicle) daily, and group II (experimental, n=21), which received 0.5 mg/kg or 0.125 mg/day of anastrozole diluted with 0.1 mL of propylene glycol. RESULTS: Light microscopy showed a higher concentration of cells with brown Ki-67 stained nuclei in the control compared to the experimental group. The mean percentage of Ki-67 stained nuclei per 500 cells in the vaginal epithelium was 68.64±2.64 and 30.46±2.00 [mean±standard error of the mean (SEM)] in the control and experimental groups, respectively (p<0.003). CONCLUSION: This study showed that anastrozole, at the dose and treatment duration selected, significantly decreased cell proliferation in the vaginal mucosa of the rats in persistent estrus.

RESUMO

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) is a low incidence disability with a multifactorial etiology and a wide array of symptoms. The main symptom is a thunderclap headache, accompanied sometimes with various neurological deficits that can lead to death. RCVS is usually diagnosed through radiological imaging technology. The treatment includes adopting general measures of monitoring, symptomatic management, identifying the etiology and acting on it to avoid recurrence. CASE REPORT: A 71-year-old woman with a history of breast cancer originally treated with tamoxifen. Due to urticaria, the anastrozole management was staggered. She was admitted for aphasia, drowsiness and a thunderclap headache. The patient reported a similar event two weeks prior admission. In brain resonance, there was evidence of small sub-arachnoidal haemorrhage (SAH) of the left parietal temporal convexity and cerebral angiography. As well as documented vasospasm in the posterior parietal region confirming the diagnosis of RCVS plus SAH. During the stay, she presented three events with the same characteristics, requiring intensive monitoring and two therapeutic panangiographies with intra-arterial nimodipine with subsequent resolution of the vessel spasm. The patient remains asymptomatic six months later. CONCLUSION: RCVS is difficult to diagnose given its wide array of symptoms and multifactorial etiology. In this case, RCVS plus SAH is associated with the use of anastrozole. So far there are no reported cases of aromatase inhibitors associated with this pathology and should be reported in the literature for pharmacovigilance.

TITLE: Sindrome de vasoconstriccion cerebral reversible asociado a anastrozol: una causa inusual de alto impacto.Introduccion. El sindrome de vasoconstriccion cerebral reversible (SVCR) es una entidad de baja incidencia, de etiologia multifactorial y amplio espectro de presentacion. El principal sintoma es la cefalea de tipo trueno. Puede estar acompañado de focalizacion neurologica y cursar con desenlaces clinicos variable que incluso pueden llevar a la muerte. El diagnostico es clinico e imaginologico, y el tratamiento incluye adoptar medidas generales de monitorizacion, manejo sintomatico, identificar la etiologia y actuar sobre ella para evitar recurrencia. Caso clinico. Mujer de 71 años con antecedente de cancer de seno, tratada inicialmente con tamoxifeno; por presentar urticaria, se escalono tratamiento con anastrozol. Ingreso por cefalea de tipo trueno, afasia anterior y somnolencia. La paciente refirio un evento similar una semana antes del ingreso. En la resonancia magnetica cerebral evidencio una hemorragia subaracnoidea (HSA) pequeña de la convexidad temporoparietal izquierda, y la panangiografia documento vasoespasmo en la region parietal posterior, lo que confirmo el diagnostico de SVCR mas HSA. Durante el ingreso presento tres eventos de iguales caracteristicas, que requirieron monitorizacion intensiva y dos panangiografias terapeuticas con nimodipino intraarterial, con posterior resolucion del vasoespasmo. Permanece asintomatica seis meses despues. Conclusion. El SVCR constituye un reto diagnostico dada su presentacion variable y su etiologia multifactorial. En este caso, el SVCR mas HSA esta asociado al uso de anastrozol. Hasta el momento no hay casos descritos de inhibidores de la aromatasa asociados a esta patologia, que debe comunicarse para su farmacovigilancia.

RESUMO

OBJECTIVE: Antiandrogen, aromatase inhibitor, and gonadotropin-releasing hormone analog (GnRHa) treatment normalizes growth rate and bone maturation and increases predicted adult height (AH) in boys with familial male-limited precocious puberty (FMPP). To evaluate the effect of long-term antiandrogen, aromatase inhibitor, and GnRHa on AH, boys with FMPP who were treated were followed to AH. STUDY DESIGN: Twenty-eight boys with FMPP, referred to the National Institutes of Health, were started on antiandrogen and aromatase inhibitor at 4.9 ± 1.5 years of age; GnRHa was added at 6.9 ± 1.5 years of age. Treatment was discontinued at 12.2 ± 0.5 years of age (bone age, 14.4 ± 1.3). AH was assessed at 16.4 ± 1.3 years of age (bone age, 18.5 ± 0.6). RESULTS: AH (mean ± SD) for all treated subjects was 173.6 ± 6.8 cm (-0.4 ± 1.0 SD relative to adult US males). For 25 subjects with pretreatment predicted AH, AH significantly exceeded predicted AH at treatment onset (173.8 ± 6.9 vs 164.9 ± 10.7 cm; P < .001), but fell short of predicted AH at treatment discontinuation (177.3 ± 9.0 cm; P < .001). For 11 subjects with maternal or sporadic inheritance, the mean AH was 3.1 cm (0.4 SD score) below sex-adjusted midparental height (175.4 ± 5.8 vs 178.5 ± 3.1 cm [midparental height]; P = .10). For 16 subjects with affected and untreated fathers, AH was significantly greater than fathers' AH (172.8 ± 7.4 vs 168.8 ± 7.2 cm; P < .05). CONCLUSIONS: Long-term treatment with antiandrogen, aromatase inhibitor, and GnRHa in boys with FMPP results in AH modestly below sex-adjusted midparental height and within the range for adult males in the general population.