Biosimilar Versus Originator Pegfilgrastim for Preventing Chemotherapy-Induced Neutropenia: A Phase III Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study.

PURPOSE: This study evaluated the efficacy, safety, and immunogenicity of biosimilar pegfilgrastim (PegFilBS) and originator pegfilgrastim (PegFilOR) in patients with stage 2-4 breast cancer. METHODS: This phase III randomized, multicenter, evaluator-blinded, noninferiority study recruited women with stage 2-4 breast cancer in Argentina who were scheduled to receive chemotherapy. Stratification was based on the breast cancer stage. The primary end point was the duration of severe neutropenia (DSN, noninferiority margin: 1 day) in the first chemotherapy cycle. Secondary end points assessed were incidence of severe neutropenia, grade 3 neutropenia, febrile neutropenia, infections, postchemotherapy hospitalization and duration, and the incidence of adverse drug reactions (ADRs). RESULTS: A total of 120 patients were randomly assigned to receive PegFilBS (58 patients) or PegFilOR (62 patients). Severe neutropenia occurred in 52 of 283 cycles (18.4%) for 27 patients who received PegFilBS and in 48 of 297 cycles (16.2%) for 20 patients who received PegFilOR (P = .48). During the first cycle, severe neutropenia occurred in 16 patients who received PegFilBS (DSN: 0.78 ± 1.53 days) and in 11 patients who received PegFilOR (DSN: 0.53 ± 1.25 days; 95% CI, -0.26 to 0.76 days). In the intention-to-treat analysis, the mean DSN values were 0.90 ± 1.79 days for the PegFilBS group and 0.50 ± 1.21 for the PegFilOR group (95% CI, -0.15 to 0.95 days). No significant differences were observed for the secondary efficacy end points. Three patients experienced seven ADRs in the PegFilBS group while 10 patients experienced 31 ADRs in the PegFilOR group. The most common ADR was myalgia. CONCLUSION: Relative to PegFilOR, PegFilBS provided noninferior efficacy outcomes in Argentinian women with stage 2-4 breast cancer who were treated using myelosuppressive chemotherapy.

Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice.

BRCA1/2 mutations in Latin America are scarcely documented and in serious need of knowledge about the spectrum of BRCA pathogenic variants, information which may alter clinical practice and subsequently improve patient outcome. In addition, the search for data on testing policies in different regions constitutes a fundamental strength for the present study, which analyzes BRCA1/2 gene sequences and large rearrangements in 940 probands with familial and/or personal history of breast/ovary cancer (BOC). In non-mutated DNA samples, Multiplex Ligation-dependent Probe Amplification assays (MLPA) were used for the analysis of large rearrangements. Our studies detected 179 deleterious mutations out of 940 (19.04%) probands, including 5 large rearrangements and 22 novel mutations. The recurrent mutations accounted for 15.08% of the total and only 2.87% of the probands analyzed, very different from a Hispanic panel previously described. IN CONCLUSION: a) this first comprehensive description of the spectrum in BRCA1/2 sheds light on the low frequency of recurrent mutations; b) this information is key in clinical practice to select adequate sequencing studies in our population, subsequently improve patient outcome and prevent damage associated to false normal reports resulting from the use of invalid population panels; c) panels of mutations from other populations should be cautiously validated before imported, even those of apparently similar origin, a concept to be considered beyond significance in Argentina.

Carcinoma micropapilar invasivo de mama: nuestra experiencia en el Hospital de Clínicas José de San Martín / Micropapillary invasive breast carcinoma: our experience at the Hospital de Clínicas José de San Martín

Introducción: El carcinoma micropapilar invasivo de la mama (CMI) es una variante agresivapoco frecuente caracterizada por gran linfotropismo y alta frecuencia de metástasis ganglionares. Se correlaciona con tumores con alto grado histológico. La expresión de receptores hormonales es similar al carcinoma ductal y el HER2/neu se encuentra elevado en mayor proporción. Objetivos: Describir nuestra experiencia con los casos de CMI diagnosticados en el servicio del hospital, detallando los factores de pronóstico y predicción de tratamientos presentes en cada caso. Material y métodos: Se analizaron 26 casos de CMI diagnosticados entre los años 2000 y 2012 en la Sección Patología Mamaria del Hospital de Clínicas José de San Martín. Resultados: De 878 pacientes, 26 casos presentaron CMI (2,96%), edad media de 66 años (37-87 años). El tamaño tumoral varió de 0,4 a 10,0 cm (mediana de 2,1 cm). El 47,6% se presentaron clínicamente como estadio III; 12 casos eran G2 (46,1%) y 14 casos G3 (53,9%). Presentó invasión linfovascular el 73% de los casos. Presentaron compromiso ganglionar 13/19 pacientes (68,4%). Los receptores de estrógeno fueron positivos en el 100% de los casos y los de progesterona en el 63,6%. El HER2/neu fue positivo en 30% de los casos (6/20). El Ki67 fue evaluado en 6 casos, siendo positivo en el 50% (3 casos). Conclusión: El CMI se manifiesta como un tumor altamente agresivo. Se presenta clínicamente con estadios avanzados, alto grado histológico y marcada invasión linfovascular del estroma, alta expresión positiva para receptores hormonales y un nivel algo superior, con respecto al carcinoma ductal, de inmunorreactividad para HER2/neu (30% vs. 15%).