Trends in Neoadjuvant Endocrine Therapy Use and Impact on Rates of Breast Conservation in Hormone Receptor-Positive Breast Cancer: A National Cancer Data Base Study.

BACKGROUND: The American College of Surgeons Oncology Group Z1031 trial demonstrated that neoadjuvant endocrine therapy (NET) increased breast-conserving surgery (BCS) rates for postmenopausal patients with clinical tumor stage 2-4c estrogen receptor-positive breast cancer. We evaluated national trends in NET use in relation to the conduct of the Z1031 trial and the impact of NET on the rates of BCS. METHODS: Using the National Cancer Data Base (NCDB), we identified all cT2-4c hormone receptor (HR)-positive breast cancer patients age ≥50 years from 2004 to 2012. The time intervals of pre-Z1031 (2004-2006), during Z1031 (2007-2009), and post-Z1031 (2010-2012) were examined, and adjusted analyses were performed using multivariable logistic regression. RESULTS: Of 77,272 patients, 2294 (3.0 %) received NET. Clinical T-stage distribution was 66,885 (86.6 %) for cT2, 7318 (9.5 %) for cT3, and 3069 (4.0 %) for cT4a-c. A small but statistically significant increase in NET use was noted, from 2.7 % pre-Z1031 to 3.2 % post-Z1031; the adjusted odds ratio (OR) for NET was 1.28 [95 % confidence interval (CI) 1.13-1.45; p < 0.001] for post-Z1031 versus pre-Z1031. NET use varied by clinical T stage, increasing from 1.8 % pre-Z1031 to 2.4 % post-Z1031 in cT2 patients (p < 0.001) and from 6.3 % pre-Z1031 to 7.4 % post-Z1031 in cT3 patients (p = 0.02). Patients receiving NET were more likely to undergo BCS compared with patients undergoing primary surgery (46.4 vs. 43.9 %; p = 0.02) with an adjusted OR of 1.60 (95 % CI 1.46-1.75; p < 0.001). CONCLUSIONS: NET use has increased slowly since the Z1031 trial; however, overall use remains low. NET significantly increased the rates of BCS in patients with HR-positive clinical T2-4c breast cancer. Clinicians should consider NET use for patients with HR-positive breast cancer interested in BCS.

Characterization of perioperative infection risk among patients undergoing radical cystectomy: Results from the national surgical quality improvement program.

OBJECTIVES: To evaluate the incidence, risk factors, and timing of infections following radical cystectomy (RC). METHODS: The American College of Surgeons National Surgical Quality Improvement Project database was queried to identify patients undergoing RC for bladder cancer from 2006 to 2013. Characteristics including year of surgery, age, sex body mass index, diabetes, smoking, renal function, steroid usage, preoperative albumin, preoperative hematocrit, perioperative blood transfusion (PBT), and operative time were assessed for association with the risk of infection within 30 days of RC using multivariable logistic regression. RESULTS: A total of 3,187 patients who had undergone RC were identified, of whom 766 (24.0%) were diagnosed with a postoperative infection, at a median of 13 days (interquartile ranges 8-19) after RC. Infections included surgical site infection (SSI) (404; 12.7%), sepsis/septic shock (405; 12.7%), and urinary tract infection (UTI) (309; 9.7%). On multivariable analysis, body mass index≥30kg/m2 (odds ratios [OR] = 1.52; P<0.01), receipt of a PBT (OR = 1.27; P<0.01), and operative time≥480 minutes (OR = 1.72; P<0.01) were significantly associated with the risk of infection. When the outcomes of UTI, SSI, and sepsis were analyzed separately, operative time≥480 minutes remained independently associated with increased infection risk in each model (OR = 2.11 for UTI, OR = 1.63 for SSI, and OR = 1.80 for sepsis/septic shock; all P<0.05), whereas PBT was associated with SSI and sepsis/septic shock (OR = 1.33 and OR = 1.29, respectively; both P< 0.05). CONCLUSIONS: Approximately 25% of patients undergoing RC experience an infection within 30 days of surgery. Several potentially modifiable risk factors for infection were identified, specifically PBT and prolonged operative time, which may represent opportunities for future care improvement.

Impact that Timing of Genetic Mutation Diagnosis has on Surgical Decision Making and Outcome for BRCA1/BRCA2 Mutation Carriers with Breast Cancer.

BACKGROUND: Deleterious BRCA mutation carriers with breast cancer are at increased risk for additional breast cancer events. This study evaluated the impact that timing of identification of BRCA+ status has on surgical decision and outcome. METHODS: The authors reviewed all BRCA carriers at their institution whose breast cancer was diagnosed between January 1996 and June 2015. Patient surveys, medical records, and institutional databases were used to collect data. Differences in surgical choice were analyzed using the chi-square test, and rates of subsequent breast cancer events were estimated using the Kaplan-Meier method. RESULTS: The study investigated 173 BRCA carriers with breast cancer (100 BRCA1, 73 BRCA2). Of the women with known BRCA mutation before surgery and unilateral stages 0 to 3 breast cancer (n = 63), 12.7 % underwent lumpectomy, 4.8 % underwent unilateral mastectomy (UM), and 82.5 % underwent bilateral mastectomy (BM). These surgical choices differed significantly (p < 0.0001) from those of patients unaware of their mutation at the time of surgery (n = 93) (51.6 % had lumpectomy, 19.4 % had UM, 29 % had BM). Of the patients with BRCA mutation identified after surgery who underwent lumpectomy or UM, 36 (59 %) of 66 underwent delayed BM. The patients with BRCA+ known before diagnosis presented with significantly lower-stage disease (p = 0.02) at diagnosis (69 % stage 0 or 1) than those whose BRCA mutation was identified after cancer diagnosis (40 % stage 0 or 1). CONCLUSIONS: The study findings showed that BRCA mutation status influences surgical decision. The rates of BM were higher for the patients with BRCA mutation known before surgery. Identification of BRCA mutation after surgery frequently leads to subsequent breast surgery. Genetic testing before surgery is important for patients at elevated risk for BRCA mutation.

Validation of the CPS + EG Staging System for Disease-Specific Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

BACKGROUND: CPS + EG staging, which incorporates estrogen receptor (ER) status and tumor grade with pretreatment clinical stage (CS) and post-treatment pathologic stage (PS), has been reported to have better correlation with outcome than classic TNM staging for patients treated with neoadjuvant chemotherapy (NAC). Our goal was to evaluate the performance of CPS + EG staging system in an external cohort treated with NAC. METHODS: We reviewed patients with stages I-IIIC breast cancer treated with NAC and surgery at our institution between 1988 and 2014. ER status, Nottingham grade, treatment, American Joint Committee on Cancer (AJCC) CS before NAC and PS after NAC, and follow-up data were collected. The discrimination of CPS + EG and pathologic AJCC stage were assessed using area under the curve (AUC) for survival data. RESULTS: A total of 769 patients were analyzed with a median follow-up of 2.6 (range 0.0-19.4) years; 103 patients died of breast cancer. Overall, the 5-year breast cancer cause-specific survival was 81.5 % [95 % confidence interval (CI) 77.6-85.5]. The 5-year, cause-specific survival by CPS + EG score was 93.8 % score 0, 89.9 % score 1, 90.7 % score 2, 84.8 % score 3, 67.7 % score 4, and 43.4 % score 5/6. CPS + EG score was significantly associated with cause-specific survival (p < 0.001) with an AUC of 0.69 (95 % CI 0.62-0.77) at 5 years. This was higher than the AUC of 0.63 (95 % CI 0.56-0.70) for AJCC PS (p = 0.10). CONCLUSIONS: This study validates the CPS + EG staging system using Nottingham grade in an external cohort. Addition of tumor biology and treatment response shows promise in improving survival estimates for patients treated with NAC.

Impact of neoadjuvant chemotherapy on pathologic axillary nodal status in HER-2 positive patients presenting with clinically node-negative disease.

OBJECTIVES: We investigated the impact of neoadjuvant chemotherapy (NAC) on axillary disease burden in clinically node-negative (cN0) HER-2 positive breast cancer patients. METHODS: We studied 215 cN0 patients with HER-2 positive tumors. Multivariable logistic regression was used to compare NAC versus primary surgery (PS) with respect to outcome of pathologic nodal disease. RESULTS: Of 215 patients, 42 (20%) received NAC. NAC use correlated with higher clinical T stage (P < 0.0001) and younger age (P = 0.03) with no difference in ER/PR status or tumor grade. Despite higher clinical T stage in the NAC group, rate of pathologic positive axillary nodes was non-significantly lower (NAC 5/42 = 11.9%, PS 27/173 = 15.6%, P = 0.54). In multivariable analysis, after adjustment for confounders including clinical T stage, age, and multifocal/multicentric disease, NAC showed significant reduction in odds of pathologic nodal disease (OR 0.26, 95%CI:0.06-0.90, P = 0.03). Further, among those with pathologic nodal disease, the number of positive nodes was lower after NAC (adjusted P = 0.03). Extranodal extension was present in 8/27 (30%) PS patients vs. 1/5 (20%) of the NAC patients (adjusted P = 0.36). CONCLUSION: NAC in cN0 HER-2 positive breast cancers reduces the rate of pathologic node-positive disease at operation and nodal disease burden and may decrease the need for axillary node dissection.

Increasing Use of Neoadjuvant Treatment for T1 and T2 HER2-Positive Tumors.

BACKGROUND: Use of targeted therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer has led to improvements in survival. Furthermore, neoadjuvant chemotherapy (NAC) with dual HER2 agents demonstrated improved pathological complete response (pCR) rates. With these data, and with US FDA approval in September 2013 of pertuzumab in the neoadjuvant setting, we hypothesized that the use of NAC for early-stage HER2-positive patients is increasing. METHODS: With Institutional Review Board approval, we reviewed 267 patients with 268 clinical T1 and T2 HER2-positive tumors treated from October 2008 to September 2014. We compared treatment in the early (October 2008-September 2013) to recent (October 2013-September 2014) periods. Statistical analysis was performed using Chi square tests. RESULTS: Mean patient age was 59 years. Clinical T stage included 6 (2%) T1mic, 11 (4%) T1a, 41 (15%) T1b, 95 (35%) T1c, and 115 (43%) T2. Targeted therapy included combinations of trastuzumab, lapatinib, pertuzumab, and neratinib. NAC use increased from 53/219 (24.2%) in the early group to 19/49 (38.8%) in the recent group (p = 0.04). Forty-two percent (8/19) of patients in the recent group received neoadjuvant pertuzumab versus 0/53 in the early group (p < 0.0001). More clinically node-negative (cN0) patients received NAC in the recent (12/41, 29.3%) versus early (20/167, 12.0%) period (p = 0.01). For T1 tumors, the use of NAC more than doubled between the two time periods (5.6-17.2%; p = 0.06), while NAC use increased from 48 to 70% for T2 tumors (p = 0.08). The overall pCR rate after NAC was 48.6% (35/72). CONCLUSIONS: NAC for HER2-positive breast cancer patients is increasing. Most striking was a substantial increase in NAC for patients with T1 tumors and cN0 disease.

On-pump coronary artery bypass graft operation: Is one crossclamp application better than two?

OBJECTIVES: Several factors may increase the risk of stroke during coronary artery bypass grafting. These include age and atherosclerosis, which are not modifiable, and aortic manipulation, which may be modifiable. This study reports our experience with variable degrees of aortic manipulation (ie, single vs double [partial occlusion] aortic crossclamp techniques) and its influence on rate of operative stroke. METHODS: We performed a retrospective review of 8497 patients treated with isolated on-pump coronary artery bypass grafting from 1993 to 2010. Demographics included an age of 66.8 ± 10.3 years and male sex in 6548 patients (77.1%). Operative technique used the single aortic crossclamp in 2051 patients (24.1%) and the partial aortic crossclamp in 6446 patients (75.9%). To adjust for differences in baseline patient characteristics, 2 propensity-matched cohorts of 1333 patients each were created using Society of Thoracic Surgeons risk calculator variables. RESULTS: In the unmatched cohorts, stroke occurred in 25 patients (1.2%) in the single aortic crossclamp cohort and in 98 patients (1.5%) in the partial aortic crossclamp cohort (P = .320). Logistic regression analysis demonstrated no significant relationship between stroke and aortic occlusion clamp technique (single clamp odds ratio, 0.80; 95% confidence interval, 0.51-1.24; P = .321). In the matched cohorts, stroke occurred in 16 patients (1.2%) in both the single and partial occlusion clamp cohorts (P = 1.00). CONCLUSIONS: Given the methods and limitations of the data analysis, the single and partial aortic crossclamp techniques result in similar rates of stroke during on-pump coronary artery bypass grafting.