Comparison of estrogens and estrogen metabolites in human breast tissue and urine

<p>Abstract</p> <p>Background</p> <p>An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens.</p> <p>Methods</p> <p>This study compares 15 estrogen and estrogen metabolite levels in breast tissue and urine of 9 women with primary breast cancer using a quantitative liquid chromatography-mass spectrometry method.</p> <p>Results</p> <p>The average levels of estrogens (estrone, 17 beta-estradiol) were significantly higher in breast tissue than in urine. Both the 2 and the 16-hydroxylation pathways were less represented in breast tissue than urine; no components of the 4-hydroxypathway were detected in breast tissue, while 4-hydroxyestrone was measured in urine. However, the 2/16 ratio was similar in urine and breast tissue. Women carrying the variant CYP1B1 genotype (Leu/Val and Val/Val) showed significantly lower overall estrogen metabolite, estrogen, and 16-hydroxylation pathway levels in breast tissue in comparison to women carrying the wild type genotype. No effect of the CYP1B1 polymorphism was observed in urinary metabolites.</p> <p>Conclusions</p> <p>The urinary 2/16 ratio seems a good approximation of the ratio observed in breast tissue. Metabolic genes may have an important role in the estrogen metabolism locally in tissues where the gene is expressed, a role that is not readily observable when urinary measurements are performed.</p

Prognostic significance of transcription factors FOXA1 and GATA-3 in ductal carcinoma in situ in terms of recurrence and estrogen receptor status

Aim: The aim was to analyze the expression of novel biological transcription markers, forkhead-box A1 (FOXA1), GATA binding protein 3 (GATA-3), and established markers such as Ki-67 (MIB-1) and human epidermal growth factor receptor 2 (HER2) in estrogen receptor (ER(+)) and ER(-) ductal carcinoma in situ (DCIS) patients with/without recurrence.Methods: Two hundred and ninety-one cases of DCIS were retrieved from our pathology database, with complete data available for 219 cases. The follow-up period is from 1988 to 2009. Recurrence is defined in terms of DCIS or invasive carcinoma (IC). No recurrence was seen in 88% (196/219) of cases; 12% (26/219) had a recurrence (IC: 13, DCIS: 13). We are reporting the results of biological marker expression in terms of recurrence and ER status.Results: Our study demonstrates strong expression of GATA-3 in the ER(+) DCIS in recurrence and nonrecurrence groups similar to previously described in IC. A reduced expression of GATA-3 was observed in ER(-) recurrence and nonrecurrence groups. A strong HER2 protein expression, as well as high proliferation index, was seen in recurrence group (DCIS and IC). FOXA1 expression is reduced across the groups though not statistically significant.Conclusion: This is the first study to analyze novel transcription markers FOXA1 and GATA-3 in DCIS. Further work needs to be done on a larger cohort of DCIS cases with recurrence to better understand, which variables are best able to predict recurrence and guide therapy decision strategies. Maintenance of FOXA1 and GATA-3 expression in ER(-) DCIS may offer new promising targets for therapy in future

Reassessing Opioid Use in Breast Surgery

This study aims to assess multimodal pain management and opioid prescribing practices in patients undergoing breast surgery. A retrospective review of patients undergoing breast surgery at an academic medical center between April 1, 2018 and September 30, 2019, was performed. Patients with a history of recent opioid use or conditions precluding use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen (APAP) were excluded. Opioid-sparing pain regimens were assessed. Opioids prescribed on discharge were recorded as oral morphine equivalents (OMEs) and concordance with the Opioid Prescribing Engagement Network (OPEN) determined. The total study population consisted of 518 patients. 358 patients underwent minor outpatient procedures (sentinel lymph node biopsy, lumpectomy, and excisional biopsy), 10-40% of whom were appropriately prescribed as per the OPEN. Perioperatively, 53.9% of patients received APAP, 24.6% NSAIDs, 20.4% gabapentin, and 0.3% blocks; intraoperatively, 95.8% received local anesthetic and 25.7% ketorolac. For mastectomy without reconstruction, 63-88% of prescriptions were concordant with the OPEN. For mastectomy with reconstruction, discharge opioids ranged from 25 to 400 OMEs with a mean of 134.4 OMEs; 25% of patients received a refill. Of all patients undergoing mastectomy ± reconstruction, 62.5% received APAP, 18.8% NSAIDs, 38.8% pregabalin, and 20.6% locoregional block perioperatively; 37.5% received local anesthetic and 15.6% ketorolac intraoperatively. Of 143 inpatient stays, 89% received APAP, 38% NSAID, and 29% benzodiazepines; 29 patients received no opioids inpatient but were still prescribed 25-200 OMEs on discharge. There is need for a multidisciplinary approach to pain management with the use of enhanced recovery after surgery protocols as potential means to standardize perioperative regimens and mitigate opioid overprescription. •A persistence in opioid overprescription exists despite established guidelines.•Perioperative multimodal pain regimens are not currently optimized.•Enhanced recovery after surgery presents opportunity for standardization.•Further study of the opioid use in immediate reconstruction is needed

Evaluation of opioid prescribing preferences among surgical residents and faculty

Background: Residents report that faculty preference is a significant driver of opioid prescribing practices. This study compared opioid prescribing preferences of surgical residents and faculty against published guidelines and actual practice and assessed perceptions in communication and transparency around these practices. Methods: Surgical residents and faculty were surveyed to evaluate the number of oxycodone tablets prescribed for common procedures. Quantities were compared between residents, faculty, Opioid Prescribing Engagement Network guidelines, and actual opioids prescribed. Frequency with which faculty communicate prescribing preferences and the desire for feedback and transparency in prescription practices were assessed. Results: Fifty-six (72%) residents and 57 (59%) faculty completed the survey. Overall, faculty preferred a median number of tablets greater than recommended by Opioid Prescribing Engagement Network in 5 procedures, while residents did so in 9 of 14 procedures. On average, across all operations, faculty reported prescribing practices compliant with Opioid Prescribing Engagement Network 56.1% of the time, whereas residents did so 47.6% of the time (P 1/4 .40). Interestingly, opioids actually prescribed were significantly less than recommended in 7 procedures. Among faculty, 62% reported often or always specifying prescription preferences to residents, while only 9% of residents noted that faculty often did so. Residents (80%) and faculty (75%) were amenable to seeing regular reports of personal opioid prescription practices, and 74% and 65% were amenable to seeing practices compared with peers. Only 34% of residents and 44% of faculty wanted prescription practices made public. Conclusion: There is a disconnect between opioid prescribing preferences and practice among surgical residents and faculty. Increased transparency through individualized reports and education regarding Opioid Prescribing Engagement Network guidelines with incorporation into the electronic medical record as practice advisories may reduce prescription variability. (c) 2021 Published by Elsevier Inc

Resident Opioid Prescribing Habits Do Not Reflect Best Practices in Post-Operative Pain Management: An Assessment of the Knowledge and Education Gap

To evaluate deficiencies in knowledge and education in opioid prescribing and to compare surgical resident opioid-prescribing practices to Opioid Prescribing Engagement Network (OPEN) procedure-specific guidelines. Anonymous web-based survey distributed to all general surgery residents to evaluate prior education received and confidence in knowledge in opioid prescribing. The number of 5 milligram oxycodone tablets prescribed for common procedures was assessed and compared with OPEN for significance using Wilcoxon signed rank tests. General surgery residency program within large university-based tertiary medical center. Categorical general surgery residents of all postgraduate years. Fifty-six of 72 (78%) categorical residents completed the survey. Few reported receiving formal education in opioid prescribing in medical school (32%) or residency (16%). While 82% of residents felt confident in opioid side effects, fewer felt the same with regards to opioid pharmacokinetics (36%) or proper opioid disposal (29%). Opioids prescribed varied widely with residents prescribing significantly more than recommended by OPEN in 9 of 14 procedures. Tackling the evolving opioid epidemic requires a multidisciplinary approach that addresses prescribing at all steps of the process, starting with trainee education