Clinical Course of Breast Cancer Patients with Local-Regional Progression During Neoadjuvant Systemic Therapy.

BACKGROUND: Neoadjuvant systemic therapy (NST) is standard for locally advanced breast cancer and is now frequently considered for those with early-stage and node-positive disease. We aimed to evaluate the treatment course and outcomes in patients with disease progression during NST. METHODS: Patients diagnosed with unilateral stage I-III breast cancer between 2005 and 2015 with documented local-regional progression while receiving NST, by clinical examination and/or imaging after two or more cycles of chemotherapy, were identified from a prospective database, stratified by receipt of surgery and outcomes analyzed. RESULTS: Of 6362 patients treated with NST during the study period, 124 (1.9%) developed disease progression. At a median live follow-up of 71 months, 23.4% were alive without disease and 70.2% had died from breast cancer. Median overall survival (OS) time for patients with progression was 26 months and median distant disease-free survival (DFS) was 14 months. Triple-negative breast cancer was associated with a higher likelihood of death (p < 0.001) and development of distant metastasis (p = 0.002). Among patients who had surgery (104, 89.3%), 40 (38.5%) developed local-regional recurrence, 67 (64.4%) developed distant metastasis, and 69 (66.3%) died from breast cancer. Median OS and median distant DFS in this subgroup was 31 and 16 months, respectively. CONCLUSIONS: High rates of local-regional and distant failure were seen following disease progression while receiving NST. This suggests aggressive tumor biology and the need to study novel systemic therapies. Poor survival outcomes despite surgical management highlight the importance of careful patient selection when considering operative intervention after progression while receiving NST.

Opioid Use after Breast-Conserving Surgery: Prospective Evaluation of Risk Factors for High Opioid Use.

BACKGROUND: Responsible opioid prescribing for postoperative pain control is critical. We sought to identify both patient and surgical factors associated with increased opioid use after breast-conserving surgery (BCS). METHODS: Patients (N = 316) undergoing BCS were surveyed to determine postoperative opioid use. Univariate and multivariate analyses were used to determine factors contributing to increased opioid use (highest quartile of use). All opioid prescriptions were converted to oral morphine equivalents (OME) for analysis. RESULTS: The mean opioid prescription was 33.2 OMEs. Fourteen patients (4.4%) did not receive a narcotic prescription at discharge. Seventy-eight patients (24.7%) did not take any opioids after discharge. Those in the highest quartile of use consumed more than 50 OMEs. Surgical factors, such as bilateral oncoplastic surgery (60.8 OMEs vs. 33.1 OMEs, p = 0.0001), axillary lymph node dissection (ALND) (61.5 vs. 30.5, p = 0.0003), and drain use (2 drains 71.1, 1 drain 40.4, no drains 26.2, p = 0.0001), were associated with higher opioid use. In a multivariate analysis, smoking, preoperative opioid use, bilateral oncoplastic surgery, high postoperative reported pain score, placement of at least one surgical drain, and receiving a discharge prescription greater than 150 OMEs were associated with the highest quartile of opioid use. CONCLUSIONS: Smoking, preoperative opioid use, bilateral oncoplastic surgery, ALND, use of surgical drains, high reported postoperative pain score, and receiving a higher OME discharge prescription are associated with higher postoperative opioid use. Given the wide variability of analgesic needs, these criteria should be used to guide the appropriate tailoring of opioid prescriptions.

A Clinical Feasibility Trial for Identification of Exceptional Responders in Whom Breast Cancer Surgery Can Be Eliminated Following Neoadjuvant Systemic Therapy.

OBJECTIVE: To determine the accuracy of fine-needle aspiration (FNA) and vacuum-assisted core biopsy (VACB) in assessing the presence of residual cancer in the breast after neoadjuvant systemic therapy (NST). SUMMARY BACKGROUND DATA: Pathologic complete response (pCR) rates after NST have improved dramatically, suggesting that surgery might be avoided in some patients. Safe avoidance of surgery would require accurate confirmation of no residual invasive/in situ carcinoma. METHODS: Forty patients with T1-3N0-3 triple-negative or HER2-positive cancer receiving NST were enrolled in this single-center prospective trial. Patients underwent ultrasound-guided or mammography-guided FNA and VACB of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting residual breast disease after NST. RESULTS: Median initial clinical tumor size was 3.3 cm (range, 1.2-7.0 cm); 16 patients (40%) had biopsy-proven nodal metastases. After NST, median clinical tumor size was 1.1 cm (range, 0-4.2 cm). Nineteen patients (47.5%) had a breast pCR and were concordant with pathologic nodal status in 97.5%. Combined FNA/VACB demonstrated an accuracy of 98% (95% CI, 87%-100%), false-negative rate of 5% (95% CI, 0%-24%), and negative predictive value of 95% (95% CI, 75%-100%) in predicting residual breast cancer. VACB alone was more accurate than FNA alone (P = 0.011). CONCLUSIONS: After NST, image-guided FNA/VACB can accurately identify patients with a breast pCR. Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.

Clostridium difficile Infections after Blunt Trauma: A Different Patient Population?

BACKGROUND: The epidemiology of Clostridium difficile-associated infection (CDI) has changed, and it is evident that susceptibility is related not only to exposures and bacterial potency, but host factors as well. Several small studies have suggested that CDI after trauma is associated with a different patient phenotype. The purpose of this study was to examine and describe the epidemiologic factors associated with C. difficile in blunt trauma patients without traumatic brain injury using the Trauma-Related Database as a part of the "Inflammation and Host Response to Injury" (Glue Grant) and the University of Florida Integrated Data Repository. METHODS: Previously recorded baseline characteristics, clinical data, and outcomes were compared between groups (67 C. difficile and 384 uncomplicated, 813 intermediate, and 761 complicated non-C. difficile patients) as defined by the Glue Grant on admission and at days seven and 14. RESULTS: The majority of CDI patients experienced complicated or intermediate clinical courses. The mean ages of all cohorts were less than 65 y and CDI patients were significantly older than uncomplicated patients without CDI. The CDI patients had increased days in the hospital and on the ventilator, as well as significantly higher new injury severity scores (NISS), and a greater percentage of patients with NISS >34 points compared with non-CDI patients. They also had greater Marshall and Denver multiple organ dysfunction scores than non-CDI uncomplicated patients, and greater creatinine, alkaline phosphatase, neutrophil count, lactic acid, and PiO2:FiO2 compared with all non-CDI cohorts on admission. In addition, the CDI patients had higher glucose concentrations and base deficit from uncomplicated patients and greater leukocytosis than complicated patients on admission. Several of these changes persisted to days seven and 14. CONCLUSION: Analysis of severe blunt trauma patients with C. difficile, as compared with non-CDI patients, reveals evidence of increased inflammation, immunosuppression, worse acute kidney injury, higher NISS, greater days in the hospital and on the ventilator, higher organ injury scores, and prolonged clinical courses. This supports reports of an increased prevalence of CDI in a younger population not believed previously to be at risk. This unique population may have specific genomic or inflammation-related risk factors that may play more important roles in disease susceptibility. Prospective analysis may allow early identification of at-risk patients, creation of novel therapeutics, and improved understanding of how and why C. difficile colonization transforms into infection after severe blunt trauma.