Defining the Biology of Estrogen Receptor-Low-Positive Breast Cancer.

BACKGROUND: We sought to better define estrogen receptor-low-positive (ER-low+) breast cancer biology and determine the utility of the Oncotype DX Breast Recurrence Score® (RS) assay in this population. METHODS: Patients with information regarding percentage ER positivity and PAM50 subtype were identified in The Cancer Genome Atlas (TCGA) and subtype distribution was determined. Next, patients with ER-low+ (ER 1-10%), HER2- breast cancer undergoing upfront surgery with known RS result were identified in the National Cancer Database (NCDB) and our institutional Dana-Farber Brigham Cancer Center (DF/BCC) database; RS distribution was examined. Finally, patients with ER-low+, HER2- breast cancer treated at DF/BCC from 2011 to 2020 without prior RS results and in whom tissue was available to perform the assay were identified. RS results, treatment, recurrence and breast cancer-specific survival (BCSS) were determined. RESULTS: Of 1033 patients in TCGA, ER percentage and PAM50 subtype were available for 342 (33.1%) patients. Forty-six (13.5%) had ER-low+/HER2- tumors, among whom 82.6% were basal and 4.3% were luminal A. Among 3423 patients with ER-low+/HER2- disease in the NCDB, RS results were available for 689 (20.1%) patients; 67% had an RS ≥26. In our institutional database, only two patients with ER-low+/HER2- disease and an RS were identified, both with RS ≥26. Among 37 patients in our institutional cohort without prior RS, 35 (97.4%) had an RS ≥26, determined with testing. After a median follow-up of 40 months (range 3-106), three patients, all treated with chemotherapy, recurred. Three-year BCSS was 97.0% (95% confidence interval 96.9-97.1%). CONCLUSIONS: Most ER-low+/HER2- breast cancers are basal-like, with RS ≥26 suggesting these tumors are similar to triple-negative disease.

Identification of Populations at Risk for "Choosing Un-Wisely": A SEER Population-Based Study.

BACKGROUND: Since 2016, the Choosing Wisely campaign has recommended against routine axillary surgery in elderly patients with early stage, hormone receptor positive (ER+) breast cancer. The objective was to evaluate factors associated with axillary surgery in breast cancer patients meeting criteria for sentinel lymph node biopsy (SLNB) omission and identify potential disparities. METHODS: Female patients age ≥70 years with cT1-2N0M0, ER+, HER2-negative breast cancer diagnosed after publication of the Choosing Wisely recommendations, between 2016 and 2019, were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patient demographics and tumor characteristics associated with axillary surgery were analyzed. RESULTS: Of the 31 756 patients meeting omission criteria, 25 771 (81.2%) underwent axillary surgery. Hispanic ethnicity, median household income between $35,000 and $70,000, treatment in rural areas, poor differentiation, lobular and mixed lobular with ductal histology, T2 tumors, radiation therapy, and systemic therapy were factors associated with receiving axillary surgery on multivariable analysis. In the axillary surgery cohort, a median of 2 (IQR = 2) nodes were examined and 529 (2.1%) patients were found to have 1 or more positive lymph nodes. DISCUSSION: Among elderly patients meeting Choosing Wisely criteria for SLNB omission, particular racial, ethnic, socioeconomic, and geographic populations may be at increased risk for potential over treatment. Identification of these factors provides specific opportunities for education and implementation of de-escalation of unnecessary procedures.

Reconstruction among patients undergoing mastectomy: the effect of surgical deserts.

BACKGROUND: Surgical deserts (SDs) are defined as the geographic maldistribution of general surgeons of six or less per 100,000 population in underserved/rural counties. Disparities have been reported in breast cancer outcomes; however, the effect of SDs remains unknown. We sought to examine the effect of SDs on breast reconstruction (BR) after mastectomy and the differences between patients in both the cohorts. METHODS: Using the Nationwide Inpatient Sample database years 2007-2011, we identified International Classification of Diseases 9th edition codes for breast cancer, mastectomy, and BR in California. SDs were identified using the American College of Surgeons Health Policy Research Institute workforce atlas. Data included patient demographics and socioeconomic status, and the primary outcome was the rates of BR. RESULTS: A total of 9325 mastectomy patients, with or without BR, were identified. Of this, 12.8% patients were in SDs, whereas 87.2% patients were in nonsurgical deserts (NSDs). Overall, 35.8% of patients received BR, whereas 64.2% did not. Of the patients in SDs, only 14% received BR, whereas in NSDs, 39% received BR. On multivariate analysis, SD patients were significantly less likely to receive BR than NSD patients (odds ratio [95% confidence interval], 0.29 [0.24-0.35]; P < 0.001). SDs had higher rates of low household income, Medicare insurance, and comorbidities. NSDs had higher rates of high household income, Health Maintenance Organization/private insurance, and lower rates of comorbidities. CONCLUSIONS: Patients in SDs are significantly less likely to receive BR. This disparity may be magnified because of differences in demographics and income levels, and decreased access to reconstructive surgeons. Interventions aimed at decreasing disparities caused by SDs are needed.

Lobular Carcinoma In Situ: A 15-Year Single Institution Review.

The optimal management of lobular carcinoma In Situ (LCIS) has largely been debated. This study evaluated practice patterns and outcomes in women diagnosed with LCIS at a single institution from 2000 to 2014. Patient characteristics, histology, method of diagnosis, and management were examined in relation to disease-free survival, and overall survival (OS). A total of 209 patients were identified. Surgical management in the majority of patients was excisional biopsy or local excision. Patients diagnosed with LCIS by core biopsy were less likely to have mastectomy as compared with other methods of initial diagnosis (P = 0.01). A total of 108 (90.8%) patients received chemoprevention (CP) counseling, and 47 (43.5%) used chemoprevention. Estimated five-year disease-free survival rate was 96.3 per cent (95% confidence interval (CI): 92.0-98.3%) and OS rate was 98.6 per cent (95% CI: 94.6-99.7%). Older age was associated with a higher risk of subsequent breast cancer (hazard ratio (HR): 1.04; 95% CI: 1.01-1.07; P = 0.01). Older age (HR: 1.06; 95% CI: 1.02-1.11; P = 0.004) and diagnosis in the earlier years of the study period (HR: 0.65; 95% CI: 0.48-0.89; P = 0.007) were significantly associated with worse OS in multivariate analysis. LCIS has a favorable prognosis and is most commonly managed conservatively.

Noncardiac surgery in patients on mechanical circulatory support.

This study examined outcomes in patients with left ventricular assist device (LVAD) and extracorporeal membrane oxygenation (ECMO) requiring noncardiac surgical procedures and identified factors that influence outcomes. All patients with mechanical circulatory support (MCS) devices at our institution from 2002 to 2013 undergoing noncardiac surgical procedures were reviewed. There were 148 patients requiring MCS during the study period, with 40 (27.0%) requiring 62 noncardiac surgical procedures. Of these, 29 (72.5%) had implantable LVAD and 11 (27.5%) were supported with ECMO. The two groups were evenly matched with regard to age (53.6 vs. 54.5 years, p = 0.87), male sex (71.4 vs. 45.5%, p = 0.16), and baseline creatinine (1.55 vs. 1.43 mg/dl, p = 0.76). Patients on ECMO had greater demand for postoperative blood products (0.8 vs. 2.8 units of packed red blood cells, p = 0.002) and greater postoperative increase in creatinine (0.07 vs. 0.44 mg/dl, p = 0.047). Median survival was markedly worse in ECMO patients. Factors associated with mortality included ECMO support, history of biventricular assist device, and postoperative blood transfusion. Preoperative aspirin was associated with survival. These findings demonstrate the importance of careful surgical hemostasis and minimizing perioperative blood transfusions in patients on MCS undergoing noncardiac surgical procedures. In addition, low-dose antiplatelet therapy should be continued perioperatively.

"Permissive hypoventilation" in a swine model of hemorrhagic shock.

BACKGROUND: Many penetrating trauma patients in severe hemorrhagic shock receive positive pressure ventilation (PPV) upon transport to definitive care, either by intubation (INT) or bag-valve mask (BVM). Using a swine hemorrhagic shock model that simulates penetrating trauma, we proposed that severely injured patients may have better outcomes with "permissive hypoventilation," where manual breaths are not given and oxygen is administrated passively via face mask (FM). We hypothesized that PPV has harmful physiologic effects in severe low-flow states and that permissive hypoventilation would result in better outcomes. METHODS: The carotid arteries of Yorkshire pigs were cannulated with a 14-gauge catheter. One group of animals (n = 6) was intubated and manually ventilated, a second received PPV via BVM (n = 7), and a third group received 100% oxygen via FM (n = 6). After placement of a Swan-Ganz catheter, the carotid catheters were opened, and the animals were exsanguinated. The primary end point was time until death. Secondary end points included central venous pressure, cardiac output, lactate levels, serum creatinine, CO2 levels, and pH measured in 10-minute intervals. RESULTS: Average survival time in the FM group (50.0 minutes) was not different from the INT (51.1 minutes) and BVM groups (48.5 minutes) (p = 0.84). Central venous pressure was higher in the FM group as compared with the INT 10 minutes into the shock phase (8.3 mm Hg vs. 5.2 mm Hg, p = 0.04). Drop in cardiac output (p < 0.001) and increase in lactate (p < 0.05) was worse in both PPV groups throughout the shock phase. Creatinine levels were higher in both PPV groups (p = 0.04). The FM group was more hypercarbic and acidotic than the two PPV groups during the shock phase (p < 0.001). CONCLUSION: Although permissive hypoventilation leads to respiratory acidosis, it results in less hemodynamic suppression and better perfusion of vital organs. In severely injured penetrating trauma patients, consideration should be given to immediate transportation without PPV.

Prehospital intubation does not decrease complications in the penetrating trauma patient.

Intubation in the prehospital setting does not result in a survival benefit in penetrating trauma. However, the effect of prehospital intubation (PHI) on the development of in-hospital complications has yet to be determined. The goal of this study was to determine if PHI in patients with penetrating trauma results in reduced mortality and in-hospital complications. Patient records for all Category 1 trauma activations as a result of penetrating injury admitted to our institution from 2006 to 2010 were reviewed. There were 1615 Category 1 trauma activations with 152 (9.8%) intubated in the field. A total of 1311 survived initial resuscitative efforts to permit hospital admission with 55 (4.2%) being intubated in the field. For patients surviving to admission, prehospital intubation was associated with increased mortality (hazard ratio, 8.266; 95% confidence interval [CI, 4.336 to 15.758; P < 0.001). After correcting for Injury Severity Score, PHI was not protective against pulmonary complications (odds ratio [OR], 0.724; 95% CI, 0.229 to 2.289; P = 0.582), deep vein thrombosis/pulmonary embolus (OR, 0.838; 95% CI, 0.281 to 2.494; P = 0.750), sepsis (OR, 0.572; 95% CI, 0.201 to 1.633; P = 0.297), wound infections (OR, 1.739; 95% CI, 0.630 to 4.782; P = 0.286), or complications of any kind (OR, 1.020; 95% CI, 0.480 to 2.166; P = 0.959). For victims of penetrating trauma, immediate transportation by emergency medical personnel may result in improved outcomes.