Breast Cancer Patient's Outcomes after Neoadjuvant Chemotherapy and Surgery at 5 and 10 Years for Stage II-III Disease.

Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. Material and Methods: A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years. Kaplan-Meier curves with a log-rank test were calculated for differences according to age, BRCA status, menopausal status, TNM, pathological and molecular surrogate subtype, 20% TIL cut-off, surgical procedure, response to chemotherapy and the presence of vascular invasion. Results: The pCR rate was 25.3% and was greater in HER2 (51.3%) and TNBC (31.7%) and in BRCA carriers (41.9%). The factors independently related to patient survival were pathology and molecular surrogate subtype, type of surgery, response to NACT and vascular invasion. BRCA status was a protective prognostic factor without reaching statistical significance, with an HR 0.5 (95%CI 0.1-1.4). Mastectomy presented a double risk of distant recurrence compared to breast-conservative surgery (BCS), supporting BCS as a safe option after NACT. After a mean follow-up of 126 (SD 43) months, luminal tumors presented a substantial difference in survival rates calculated at 5 or 10 years (81.2% compared to 74.7%), whereas that for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to the response in patients with pCR, who exhibited a 10 years DDFS of 95.5% vs. 72.4% for those patients without pCR, p < 0001. This difference was especially meaningful in TNBC: the 10 years DDFS according to an RCB of 0 to 3 was 100%, 80.6%, 69% and 49.2%, respectively, p < 0001. Patients with a particularly poor prognosis were those with lobular carcinomas, with a 10 years DDFS of 42.9% vs. 79.7% for ductal carcinomas, p = 0.001, and patients with vascular invasion at the surgical specimen, with a 10 years DDFS of 59.2% vs. 83.6% for those patients without vascular invasion, p < 0.001. Remarkably, BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Conclusions: Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions.

The Mode of Grass Supply to Dairy Cows Impacts on Fatty Acid and Antioxidant Profile of Milk.

The optimization of milk production includes a rational use of forages, respect for the environment and offers the best quality to consumers. Milk production based on grass and forages produces healthier milk and it is widely spread throughout the Atlantic arc to maximize milk yield per hectare. However, the mode of offering the grass can have a major influence on milk composition. The aim of this study was to evaluate the effect of grass supply mode (grazing, zero-grazing or ensiling) on dairy cows' performance, with particular reference to fatty acids and fat-soluble antioxidants concentration. A three by three Latin square experiment was performed with 18 dairy cows. Experimental treatments consisted of exclusive feeding with grass silage and zero-grazing, both offered ad libitum indoors, or grazing for 24 h. The results showed that grazing cows had a higher dry matter intake and greater milk yield than cows feeding on grass silage and zero-grazing, as well as higher concentrations of protein, lactose, nonfat-solids and urea in milk than housed cows. Milk fat from grazing cows had a higher proportion of unsaturated fatty acids than from cows feeding on grass silage and zero-grazing, with significant differences in the proportion of vaccenic and rumenic acids. The 18:1 trans-11 to 18:1 trans-10 ratio is proposed as biomarker to identify the milk produced from the management system of grazing cattle. Milk from grazing cows had a greater proportion of lutein than cows eating grass silage, with the zero-grazing system having intermediate values. In conclusion, the mode of grass supply affects fatty acid and antioxidant profiles of milk.

Correction: Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness.

[This corrects the article DOI: 10.1371/journal.pone.0132546.].

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness.

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.

Obstructive sleep apnea in normal weight patients: characteristics and comparison with overweight and obese patients.

OBJECTIVE: To determine the frequency of obstructive sleep apnoea (OSA) and metabolic syndrome (MS) in normal weight patients and their characteristics, and to compare these with overweight and obese patients. METHODS: We studied all patients with suspected OSA referred to the sleep laboratory from January to December 2009. OSA was diagnosed when the apnoea-hypopnoea index (AHI) was >5 and symptoms were present. MS was diagnosed according to International Diabetes Federation (IDF) criteria. The patients were distributed into 3 groups according to body mass index (BMI): normal weight (<25kg/m(2)), overweight (25-29.9kg/m(2)) and obese (≥30kg/m(2)). RESULTS: We studied 475 patients: 7.60% normal weight and 56.4% obese. Most patients in the normal weight group were women, snorers, non-smokers, non-drinkers and were significantly younger and with a smaller neck and waist circumference than obese and overweight patients. OSA was diagnosed in 90.10%: 77.70% normal weight. OSA in these patients was mostly mild, and there were differences between the diagnosis of OSA and the BMI classified. MS was diagnosed in 64.40%: 33.33% normal weight. There was a higher probability of MS as the BMI increased. OSA and MS frequency in normal weight patients was 22% and in obese patients was 70.52%. OSA in normal weight patients was related with gender and age. There was no relationship between OSA and MS, or between otorhinolaryngological malformations and OSA in normal weight patients. Eight normal weight patients with OSA were treated with continuous positive airway pressure (CPAP) therapy. CONCLUSIONS: The frequency of OSA in normal weight patients was lower than in overweight and obese patients. The frequency of concomitant OSA and MS was lower in normal weight patients than in obese subjects. Normal weight patients were mostly women, younger and had no toxic habits. In normal weight patients, age and gender were predictive factors for OSA, but OSA and MS were not related.

[Prevalence of neural tube defects in Asturias (Spain): impact of prenatal diagnosis]. / Frecuencia de los defectos del tubo neural en Asturias: impacto del diagnóstico prenatal.

OBJECTIVE: To describe the frequency and prevalence trend for neural tube defects (NTD) (anencephaly, spina bifida and encephalocele) in Asturias (Spain), as well as the impact of prenatal diagnosis programs. METHODS: All cases of NTD in births and induced abortions were studied, using data from the Registry of Congenital Defects of Asturias for 1990-2004. Total and birth prevalence rates were calculated. RESULTS: The prevalence of NTD for 1990-2004 was 12.2 per 10,000 births (5.9 anencephaly, 5.0 spina bifida and 1.3 encephalocele) and showed a slightly decreasing trend due to a significant decline in spina bifida prevalence. The prevalence of anencephaly and encephalocele remained stable. The percentage of induced abortions after prenatal diagnosis among all NTD was 88% (anencephaly 96.7%, spina bifida 80% and encephalocele 84.6%), leading to a very low birth prevalence (1.4 per 10,000) for the entire period. CONCLUSIONS: The total prevalence of spina bifida has decreased in the last 15 years in Asturias. Secondary prevention through prenatal diagnosis and interruption of affected pregnancies have resulted in a marked decrease in NTD at birth. The recommendation of periconceptional use of folic acid seems not to have achieved the desired effect.