Intensive breast screening in BRCA2 mutation carriers is associated with reduced breast cancer specific and all cause mortality.

BACKGROUND: The addition of annual MRI screening to mammography has heightened optimism that intensive screening along with improved treatments may substantially improve life expectancy of women at high risk of breast cancer. However, survival data from BRCA2 mutation carriers undergoing intensive combined breast screening are scarce. METHODS: We have collated the results of screening with either annual mammography or mammography with MRI in female BRCA2 mutation carriers in Manchester and Oslo and use a Manchester control group of BRCA2 mutation carriers who had their first breast cancer diagnosed without intensive screening. RESULTS: Eighty-seven BRCA2 mutation carriers had undergone combined (n = 34) or mammography (n = 53) screening compared to 274 without such intensive screening. Ten year breast cancer specific survival was 100 % in the combined group (95 % CI 82.5-100 %) and 85.5 % (95 % CI 72.6-98.4 %) in the mammography group compared to 74.6 % (95 % CI 66.6-82.6 %) in the control group. Better survival was driven by lymph node status (negative in 67 % of screened vs 39 % of unscreened women; p < 0.001) and a significantly greater proportion of intensively screened women had invasive breast cancers <2 cm at diagnosis (74.6 % vs 50.4 %; p = 0.002). CONCLUSION: Intensive combined breast cancer screening with annual MRI and mammography appears to improve survival from breast cancer in BRCA2 mutation carriers. Data from larger groups are required to confirm the effectiveness of combined screening in BRCA2 carriers.

Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients.

Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. However, its clinical significance remains to be established. In this study, the main aims were to discover whether reclassification of breast cancer into molecular subtypes provides more precise information regarding outcome compared to conventional histopathological grading and to study breast cancer-specific survival in the different molecular subtypes. Cases of breast cancer occurring in a cohort of women born between 1886 and 1928 with long-term follow-up were included in the study. Tissue microarrays were constructed from archival formalin-fixed, paraffin-embedded tissue from 909 cases. Using immunohistochemistry and in situ hybridisation as surrogates for gene expression analyses, all cases were reclassified into the following molecular subtypes: Luminal A; Luminal B (HER2-); Luminal B (HER2+); HER2 subtype; Basal phenotype; and five negative phenotype. Kaplan-Meier survival curves and Cox proportional hazards models were used in the analyses. During the first 5 years after diagnosis, there were significant differences in prognosis according to molecular subtypes with the best survival for the Luminal A subtype and the worst for HER2 and five negative phenotype. In this historic cohort of women with breast cancer, differences in breast cancer-specific survival according to subtype occur almost exclusively amongst the histopathological grade 2 tumours. From 5 years after time of diagnosis until the end of follow-up, there appears to be no difference in survival according to molecular subtype or histopathological grade.

Risk of recurrence following delayed large flap reconstruction after mastectomy for breast cancer.

BACKGROUND: The aim of this retrospective matched cohort study was to evaluate the rate of recurrence among women with delayed large flap breast reconstruction after mastectomy for breast cancer. The recurrence rate among women treated at a single hospital was compared with that in an individually matched control group of women with breast cancer who did not have reconstruction after mastectomy. METHODS: Between 1982 and 2001, 125 women with previous invasive breast carcinoma underwent delayed large flap breast reconstruction with pedicled musculocutaneous or microvascular flaps (a median of 32 months after mastectomy). They were matched individually with 182 women with breast cancer who had a mastectomy but did not undergo breast reconstruction. Matching criteria were year of diagnosis, age at diagnosis and treating hospital. Medical records were evaluated until October 2007. Histopathological specimens for all included women were re-evaluated. The endpoint was locoregional or distant breast cancer recurrence. The risk of recurrent disease was calculated using a Cox proportional hazards analysis, adjusted for established prognostic factors. RESULTS: Median follow-up for the entire cohort was 146 months. The reconstruction group had a 2·08 (95 per cent confidence interval 1·07 to 4·06) times higher risk of recurrent disease than the mastectomy only group. CONCLUSION: Women with breast cancer who had delayed reconstruction with a large flap in this study had a higher risk of recurrent disease than those with mastectomy alone.

Topical moistening of mastectomy wounds with diluted tranexamic acid to reduce bleeding: randomized clinical trial.

BACKGROUND: Topical administration of tranexamic acid (TXA) may be an alternative to intravenous administration to reduce bleeding with a lower risk of systemic adverse events. The aim of this study was to investigate whether moistening a surgical wound with TXA before closure, leaving a thin film of drug only, would reduce postoperative bleeding. METHODS: This was a two-centre, stratified, parallel-group, placebo-controlled, double-blind RCT. Patients undergoing mastectomy with or without axillary lymph node clearance were randomized 1 : 1 to moistening of wound surface before closure with either 25 mg/ml TXA or 0·9 per cent sodium chloride (placebo). The primary endpoint was postoperative bleeding as measured by drain production in the first 24 h. Secondary endpoints were early haematoma, total drain production, postoperative complications and late aspirations of seroma within 3 months. RESULTS: Between 1 January 2016 and 31 August 2018, 208 patients were randomized. Two patients were converted to a different surgical procedure at surgery, and four did not receive the intervention owing to technical error. Thus, 202 patients were included in the study (101 in the TXA and 101 in the placebo group). TXA reduced mean drain production at 24 h (110 versus 144 ml; mean difference 34 (95 per cent c.i. 8 to 60) ml, P = 0·011). One patient in the TXA group had early haematoma compared with seven in the placebo group (odds ratio (OR) 0·13 (95 per cent c.i. 0·02 to 1·07); P = 0·057). There was no significant difference in postoperative complications between TXA and placebo (13 versus 10; OR 1·11 (0·45 to 2·73), P = 0·824) or need for late seroma aspirations (79 versus 67 per cent; OR 1·83 (0·91 to 3·68), P = 0·089). CONCLUSION: Moistening the wound with TXA 25 mg/ml before closure reduces postoperative bleeding within the first 24 h in patients undergoing mastectomy. Registration number: NCT02627560 (https://clinicaltrials.gov).

ANTECEDENTES: La administración tópica de ácido tranexámico (tranexamic acid, TXA) puede ser una alternativa a la administración por vía intravenosa para reducir la hemorragia, con menor riesgo de eventos sistémicos adversos. El objetivo de este estudio fue investigar si humedecer la herida quirúrgica con TXA 25 mg/ml antes del cierre de la incisión dejando solo una fina película de fármaco, reducía la hemorragia postoperatoria. MÉTODOS: Se trata de un ensayo clínico aleatorizado, a doble ciego, controlado con placebo, de grupos paralelos, estratificado por dos centros. Las pacientes sometidas a mastectomía con/sin resección de los ganglios linfáticos axilares se asignaron al azar 1:1 para la humidificación de la superficie de la herida antes del cierre con TXA 25 mg/ml o con NaCl al 0,9% (placebo). El objetivo primario fue la hemorragia postoperatoria medida por el débito del drenaje durante las primeras 24 horas. Los objetivos secundarios fueron el desarrollo de hematoma precoz, el débito total del drenaje, las complicaciones postoperatorias y la necesidad de aspiración de un seroma tardío durante los primeros 3 meses tras la cirugía. RESULTADOS: Entre el 1 de enero de 2016 y el 31 de agosto de 2018, 208 pacientes fueron asignadas al azar. En dos pacientes tuvo que realizarse un procedimiento quirúrgico diferente durante el periodo perioperatorio y cuatro pacientes no recibieron la intervención por errores técnicos. Por lo tanto, se incluyeron 202 pacientes en el estudio (101 fueron tratadas con TXA y 101 con placebo). El TXA redujo el débito medio del drenaje a las 24 horas (110 versus 144 ml, diferencia media 34 ml, i.c. del 95%: 8 a 60 ml, P = 0,010). Se presentó un hematoma precoz en una paciente del grupo del TXA versus siete pacientes tratadas con placebo (razón de oportunidades, odds ratio, OR 0,13, i.c. del 95% 0,02-1,07, P = 0,057). No hubo diferencias significativas en las complicaciones postoperatorias entre TXA y placebo (13 versus 10, OR 1,11, i.c. del 95% 0,45-2,73, P = 0,824) o la necesidad de aspiración tardía de seromas (79,3 versus 66,6%, OR 1,83, i.c. del 95% 0,91-3,68, P = 0,089). CONCLUSIÓN: Humedecer la herida antes del cierre con TXA 25 mg/ml reduce la hemorragia postoperatoria durante las primeras 24 horas en pacientes sometidas a mastectomía.

Changes in bone and lipid metabolism in postmenopausal women with early breast cancer after terminating 2-year treatment with exemestane: a randomised, placebo-controlled study.

Aromatase inhibitors improve relapse-free survival in early breast cancer, but there is concern about possible detrimental effects on bone mineral density (BMD) and plasma lipids. This paper presents the results of a 2-year study evaluating the effects of exemestane versus placebo on BMD, bone markers, plasma lipids and coagulation factors, including a 1-year follow-up after termination of treatment in 147 patients. During treatment, the mean annual rate of loss of BMD in the lumbar spine was 2.17% in the exemestane group versus 1.84% in the placebo group (n.s.) and 2.72% versus 1.48%, respectively, in the femoral neck (P=0.024). A loss of BMD above that expected in both arms of this study could be due to low vitamin D status (88% of all patients had vitamin D levels <30 ng/ml). The changes observed with exemestane were partially reversed during a 1-year follow-up, with no significant difference between the two arms. Similarly, the moderate decrease in high-density lipoprotein (HDL)-cholesterol was reversed. The bone marker values decreased, although a difference at 6 months of follow-up was still recorded, in particular for the markers of bone synthesis.

Surgery for ruptured abdominal aortic aneurysm and early mortality in women. Risk factors and complication profile.

AIM: Repair of ruptured abdominal aortic aneurysm (rAAA) is reported to have a higher mortality in women than in men. The aim was to study whether this difference could be verified in our institution and secondary if difference in risk- and complication profiles could explain the higher 30 day mortality after surgery for rAAA in women. METHODS: During the period 1983-2009 1649 patients, 1348 men and 301 women, were operated consecutively for infrarenal abdominal aortic aneurysm (AAA); 430 patients had rAAA, 98 women and 332 men. Co-morbidities were identified from the patients' medical records. Outcome measures within 30 days were mortality, cardiac disease (heart attack, heart failure), cerebrovascular disease (stroke, TIA), renal insufficiency (serum creatinine >140 µmol/L), major amputation, bowel infarction, pancreatitis and graft related complications. RESULTS: Compared to men, women had higher 30 d mortality after surgery for rAAA (54.1% vs. 36.3%, P=0.002). Women were significantly older than men (76 years vs. 73 years, P=0.001). In the period 1995-2009 women had more autoimmune diseases than men (P=0.045). There was no significant difference between men and women for the other measured outcomes. CONCLUSION: During the period 1995-2009, autoimmune disease were more common among women than men. For all other parameters recorded, there were no differences in risk - or complication profile that could explain the higher 30 d mortality in female patients after surgery for rAAA.