C19 steroids are converted to estrogens in a number of tissues by a specific form of cytochrome P450, namely aromatase cytochrome P450 (P450arom). Adipose tissue is the principal site of estrogen formation in postmenopausal women. Aromatase activity as well as P450arom transcripts primarily reside in the stromal cell component of the adipose tissue. Studies designed to investigate whether increased local aromatase activity in breast adipose tissue influences the growth of breast cancers have yielded discrepant results. In an attempt to clarify this controversy, adipose tissue was obtained from the four breast quadrants at the time of mastectomy (n = 13) performed for removal of a tumor. Breast fat P450arom messenger RNA levels were quantified and compared between the four quadrants within each specimen using competitive polymerase chain reaction after reverse transcription in which 10 micrograms human adipose total RNA together with 1 pg rat complementary RNA (internal standard) were reverse transcribed and coamplified. In 9 out of 13 patients (69%), highest P450arom transcript levels colocalized to the quadrants bearing tumors. This correlation was statistically significant (P < 0.001). The regional distribution of P450arom transcripts in breast adipose tissue of disease-free individuals, obtained during reduction mammoplasty (control group, n = 9), did not favor any particular region of the breast. We also quantified by morphometry the histological components of the adipose tissue samples from each quadrant in mastectomy specimens. The distribution of stromal cells significantly correlated with the distribution of P450arom transcript levels, in that quadrants containing highest proportions of stromal cells matched to highest transcript levels (P < 0.01). Although the quadrants bearing tumors contained the highest percentage of stromal cells, this correlation was not statistically significant. The adipose tissue surrounding a breast tumor displays increased estrogen biosynthesis, which may promote tumor growth. It is further suggested that the distribution of stromal cell components in breast adipose tissue gives rise to locally elevated P450arom expression, which in turn may favor neoplastic development and growth in these predisposed areas of the breast. The correlation between the presence of a tumor and elevated P450arom levels in the proximal adipose tissue is independent of tumor size, node involvement, histological type or grade, estrogen/progesterone receptor status, DNA index, or S-phase fraction.
Background The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown.
Local production of estrogen in breast tissue may influence the growth of breast cancers. Peripheral conversion of C19 steroids to estrogens is catalyzed by the aromatase enzyme complex which is comprised of a specific form of cytochrome P450, aromatase cytochrome P450 (P450AROM) and the flavoprotein, NADPH-cytochrome P450 reductase. To evaluate P450AROM mRNA levels in breast tissue, a specific competitive polymerase chain reaction amplification procedure was devised. In this method, a rat P450AROM complementary RNA is coamplified as an internal standard in order to compare amplification reactions. The amplification products are recognized by hybridization with 32P-labeled oligonucleotides specific for each species. Densitometry is used to quantitate autoradiographs. Initial studies using RNA from whole breast tissue obtained from reduction mammoplasty revealed linearity of the relationship between the densitometer signal from the human amplification product and total RNA concentration. Breast tissue was then separated into a floating adipocyte fraction and a pelleted fraction containing the other cellular elements by collagenase digestion and centrifugation. Comparison of specific content of aromatase amplification product per unit weight of RNA extracted from adipocytes and pelleted cells revealed considerably higher levels in the RNA from the nonadipocyte fraction. Immunocytochemical characterization of this fraction revealed the presence of several cell types including macrophages, ductal epithelial cells, and endothelial cells, but primary cells of stromal origin.
The Australian National Non-Acute Inpatient Project (NAIP) reported its findings on casemix in rehabilitation and slow stream geriatric medicine in October 1992. It proposed a per diem NAIP classification of 19 classes using six major clinical groups and the resource utilisation groups version three activities of daily living index (RUG III ADL index). Weightings were determined based on time spent by clinical staff in treating these patients. A quality management study was undertaken in the rehabilitation, geriatrics, and palliative care wards of the Illawarra Area Health Service for three months in 1993, analysing length of stay and cost against the predictive weights of the NAIP classification. The study concluded that this classification was an acceptable predictor of per diem costs of care in these wards of the Illawarra but was not a good predictor of length of stay.
The aromatase enzyme complex is responsible for the conversion of C19 steroids to estrogens. Aromatase activities ranging from moderate to very low have been measured in human fetal tissues. The inability to demonstrate aromatase cytochrome P450 (P450AROM) messenger RNA (mRNA) in several fetal tissues by northern blotting has been attributed to low levels of specific message. In order to identify and compare P450AROM mRNA levels in fetal tissues, we developed a specific competitive polymerase chain reaction amplification technique. This reaction uses coamplification of a rat P450AROM complementary RNA to normalize differences in amplification efficiencies. Using this technique, P450AROM mRNA was identified in all fetal tissues studied including; liver, lung, brain, skin, intestine, kidney, spleen, and heart. Fetal liver contained far more P450AROM mRNA per total RNA than any other tissues studied. Fetal brain and intestine also tended to have slightly higher levels than other tissues.
Background Recommendations for mastectomy by multidisciplinary teams (MDTs) may contribute to variation in mastectomy rates. The primary aim of this multicentre prospective observational study was to describe current practice in MDT decision-making for recommending mastectomy. A secondary aim was to determine factors contributing to variation in mastectomy rates. Methods Consecutive patients undergoing mastectomy between 1 June 2015 and 29 February 2016 at participating units across the UK were recruited. Details of neoadjuvant systemic treatment (NST), operative and oncological data, and rationale for recommending mastectomy by MDTs were collected. Results Overall, 1776 women with breast cancer underwent 1823 mastectomies at 68 units. Mastectomy was advised by MDTs for 1402 (76·9 per cent) of these lesions. The most common reasons for advising mastectomy were large tumour to breast size ratio (530 women, 29·1 per cent) and multicentric disease (372, 20·4 per cent). In total, 202 postmenopausal women with oestrogen receptor-positive (ER+) unifocal tumours were advised mastectomy and not offered NST, owing to large tumour to breast size ratio in 173 women (85·6 per cent). Seventy-five women aged less than 70 years with human epidermal growth factor receptor 2-positive (HER2+) tumours were advised mastectomy and not offered NST, owing to large tumour to breast size ratio in 45 women (60 per cent). Conclusion Most mastectomies are advised for large tumour to breast size ratio, but there is an inconsistency in the use of NST to downsize tumours in patients with large ER+ or HER2+ cancers. The application of standardized recommendations for NST could reduce the number of mastectomies advised by MDTs.
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