Evolving indications and long-term oncological outcomes of risk-reducing bilateral nipple-sparing mastectomy.

Background: Bilateral nipple-sparing mastectomy (NSM) is a technically feasible operation and is associated with excellent cosmetic outcomes. The aim of this study was to evaluate trends in patient characteristics, indications for surgery and long-term outcomes of bilateral NSM for breast cancer risk reduction over time. Methods: A review of a single-centre experience with bilateral NSM performed between 2001 and 2017 for breast cancer risk reduction in patients without breast cancer was performed. Trends in patient characteristics and indications for surgery were evaluated over four time intervals: 2001-2005, 2006-2009, 2010-2013 and 2014-2017. Statistical analysis was performed using χ2 tests. Results: Over the study period, 272 NSMs were performed in 136 patients; their median age was 41 years. The number of bilateral NSMs performed increased over time. The most common indication was a mutation in breast cancer-associated genes (104 patients, 76·5 per cent), which included BRCA1 (62 patients), BRCA2 (35), PTEN (2), TP53 (3) and ATM (2). Other indications were family history of breast cancer (19 patients, 14·0 per cent), lobular carcinoma in situ (10, 7·4 per cent) and a history of mantle irradiation (3, 2·2 per cent). The proportion of patients having a bilateral NSM for mutation in a breast cancer-associated gene increased over time (2001-2005: 2 of 12; 2006-2009: 9 of 17; 2010-2013: 34 of 41; 2014-2017: 61 of 66; P < 0·001). Mean follow-up was 53 months; no breast cancers were found during follow-up. Conclusion: The use of bilateral NSM for breast cancer risk reduction is increasing and the indications have evolved over the past 16 years. These excellent long-term oncological results suggest that bilateral NSM is a good option for surgical breast cancer risk reduction.

A multi-institutional analysis of intraoperative radiotherapy for early breast cancer: Does age matter?

BACKGROUND: Single-session intraoperative radiation therapy (IORT) minimizes treatment demands associated with traditional whole breast radiation therapy (WBRT) but outcomes on local disease control and morbidity among the elderly is limited. METHODS: A multi-institutional retrospective registry was established from 19 centers utilizing IORT from 2007 to 2013. Patient, tumor, and treatment variables were analyzed for ages <70 and ≥70. RESULTS: We evaluated 686 patients (<70 = 424; ≥70 = 262) who were margin and lymph node negative. Patients <70 were more likely to have longer operative time, oncoplastic closure, higher rates of IORT used as planned boost, and receive chemotherapy and post-operative WBRT. Wound complication rates were low and not significantly different between age groups. Median follow-up was 1.06 (range 0.51-1.9) years for < 70 and 1.01 (range 0.5-1.68) years for ≥ 70. There were 5 (0.73%) breast recurrences (4 in <70 and 1 ≥ 70, p = 0.65) and no axillary recurrences during follow-up. CONCLUSIONS: IORT was associated with a low rate of wound complication and local recurrence on short-term follow-up in this cohort.

Inmunogenicidad, inocuidad y eficacia de una vacuna tetravalente obtenida por recombinación genética de rotavirus aislados de monos rhesus y seres humanos en Belém, Brasil / Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil

Se evaluó la inocuidad, inmunogenicidad y eficacia de una vacuna tetravalente obtenida por recombinación genética de rotavirus aislados de monos rhesus y seres humanos (RRV-TV) (4 x 104 unidades formadoras de placas por dosis) en un ensayo prospectivo, aleatorio, a doble ciego y controlado con placebo que se efectuó con 540 lactantes brasileños. Se administraron dosis de vacuna o de placebo a la edad de 1, 3 y 5 meses. No se observaron diferencias significativas en la frecuencia de diarrea o vómito en los bebés de ninguno de los dos grupos después de administrar la dosis correspondiente. De 2 a 3% de los vacunados tuvieron fiebre baja los días tercero a quinto después de recibir la primera dosis, pero no después de las dosis segunda o tercera. Se observó una respuesta de anticuerpos del tipo IgA al rotavirus aislado de monos rhesus (RRV) en 58% de los vacunados y en 33% de quienes recibieron placebo. La respuesta de anticuerpos neutralizantes a cada serotipo no pasó de 20% cuando se determinó con la prueba de reducción de focos de fluorescencia, pero fue superior a 40% al medirse con la prueba de neutralización a base de reducción de placas. Se presentaron 91 casos de diarrea causada por rotavirus entre los niños que recibieron las tres dosis (de vacuna o de placebo) durante un seguimiento de 2 años, 36 de ellos en los niños vacunados. La eficacia general de la vacuna fue de 8% (P = 0,005) contra toda clase de diarrea y de 35% (P = 0,03) contra la diarrea causada por rotavirus. La protección durante el primer año de seguimiento, cuando predominó el rotavirus G del serotipo 1, fue de 57% (P = 0,008), pero se redujo a 12% en el segundo año. Se obtuvieron resultados similares al restringir el análisis a episodios en que el rotavirus fue el único agente patógeno identificado. Se observó en la vacuna una mayor tendencia a proteger contra casos de enfermedad con un promedio de seis o más deposiciones diarias. Estos resultados son lo suficientemente...

A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 104 plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages, 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3­5 in 2­3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy.