A Reappraisal of the Comparative Effectiveness of Lumpectomy Versus Mastectomy on Breast Cancer Survival: A Propensity Score-Matched Update From the National Cancer Data Base (NCDB).

BACKGROUND: Recent observational studies are concerning because they document rising mastectomy rates coinciding with more than a dozen reports that lumpectomy has better overall survival (OS) than mastectomy. Our aim was to determine if there were differences in OS of matched breast cancer patients undergoing lumpectomy versus mastectomy in the National Cancer Database (NCDB). PATIENTS AND METHODS: A retrospective cohort of patients with stage I-III breast cancer in the NCDB (2004-2013) was identified. Propensity score matching (PSM), Kaplan-Meier, and multivariate Cox proportional hazards models were used to examine OS by type of surgery. RESULTS: Of 845,136 patients, 464,052 (54.9%) underwent lumpectomy and 381,084 (45.1%) underwent mastectomy. After PSM, the hazard ratio (HR) and confidence interval (CI) for OS in all patients comparing lumpectomy with mastectomy was 1.02 (CI, 1.00-1.04; P = .002). In patients with stage I, II, and III, they were HR 1.27 (CI, 1.23-1.36; P < .001), HR 0.98 (CI, 0.95-1.01; P = .21), and HR 0.83 (CI, 0.80-0.86; P < .001), respectively. In subgroup analyses of all patients by estrogen receptor (ER) status, they were HR 1.05 (CI, 1.03-1.07; P < .001) and HR 1.00 (CI, 0.96-1.03; P = .65) in ER+ and ER- patients. CONCLUSION: In our primary model of all stage I-III matched patients, using the most recent NCDB data and the largest observational sample size to date, the OS after mastectomy was not inferior to lumpectomy. This finding can be reassuring to patients and providers. In subgroup analyses, the association between type of surgery and OS differed by cancer stage and hormone receptor status.

A US Registry-Based Assessment of Use and Impact of Chemotherapy in Stage I HER2-Positive Breast Cancer.

Background: Despite the paucity of evidence supporting chemotherapy in the treatment of node-negative, HER2-positive breast cancer measuring <2 cm, use of trastuzumab-based chemotherapy has increased over the past decade. Therefore, we used the National Cancer Database to evaluate the use and impact of chemotherapy on survival in this population. Methods: We identified female patients aged 18 to 70 years with node-negative, HER2-positive breast cancer measuring <2 cm. A propensity-matched cohort model was used to control for risk factors known to influence survival. Primary end points assessed were receipt of chemotherapy and overall survival (OS). Results: In our propensity-matched cohort model (n=8,222), adjuvant chemotherapy (ACT) was associated with a lower 5-year OS rate in T1mi breast cancer (n=626; 89.1% [95% CI, 81.8%-93.5%] vs 99.1% [96.6%-99.8%]), no significant effect in T1a disease (n=2,901; 95.4% [93.2%-96.9%] vs 96.9% [94.1%-98.3%]), and improved 5-year OS in T1b (n=2,340; 97.1% [95.1%-98.4%] vs 92.3% [88.5%-94.9%]) and T1c tumors (n=2,355; 95.9% [93.5%-97.5%] vs 91.5% [88.4%-93.9%]). In the entire cohort of 21,148 patients who met the inclusion criteria, ACT was associated with lower 5-year OS in T1mi (89.6% [83.7%-93.4%] vs 98.1% [96.6%-98.9%]) and T1a tumors (94.9% [92.9%-96.3%] vs 96.5% [94.6%-97.7%]), and improved 5-year OS in T1b (96.8% [95.6%-97.7%] vs 92.3% [88.7%-94.8%]) and T1c tumors (95.8% [94.9%-96.5%] vs 91.6% [88.5%-93.9%]). Increased use of ACT was observed over the study period. From 2010 to 2013, annual treatment rates were 71.5%, 72.4%, 73.3%, and 74.4%, respectively (trend test, P<.0001). Conclusions: Our data support the use of ACT for HER2-positive, node-negative T1b and T1c breast cancer, whereas no benefit was observed for ACT in T1mi and T1a HER2-positive, node-negative breast cancer. Although use of ACT is increasing in node-negative, HER2-positive breast cancer <2 cm, our findings caution against its use in the smallest of these tumors (T1mi and T1a) due to lack of survival benefit.

A Strategy for Changing Adherence to National Guidelines for Decreasing Laboratory Testing for Early Breast Cancer Patients.

INTRODUCTION: Past studies indicate delays in adoption of consensus-based guideline updates. In June 2016, the National Comprehensive Cancer Network changed its guidelines from routine testing to omission of ordering complete blood cell count (CBC) and liver function tests (LFT) in patients with early breast cancer. In response, we developed an implementation strategy to discontinue our historical practice of routine ordering of these tests in asymptomatic patients. METHODS: The ordering of CBC and LFT for clinical stage I-IIIA breast cancer patients was audited in 2016. In June 2016, we utilized the levers of the National Quality Strategy implementation methodology to enact a system-wide change to omit routine ordering. To measure the plan's effectiveness, guideline compliance for ordering was tracked continually. RESULTS: Of 92 patients with early stage cancer in 2016, the overall rate of compliance with guidelines for ordering a CBC and LFT was 82% (88/107) and 87% (93/107), respectively. Segregated by the pre- and post-guideline change time period, the compliance rates for ordering a CBC and LFT were 78% and 87% (P = 0.076). CONCLUSION: In contrast to historical reports of delays in adoption of new evidence-based guideline changes, we were able to quickly change provider practice during the transition from routine ordering to omission of ordering screening blood tests in newly diagnosed patients with early breast cancer.

Fewer Reoperations After Lumpectomy for Breast Cancer with Neoadjuvant Rather than Adjuvant Chemotherapy: A Report from the National Cancer Database.

BACKGROUND: Reoperations occur frequently after initial lumpectomy for breast cancer. The authors hypothesized that the receipt of neoadjuvant chemotherapy (NAC) is associated with fewer reoperations. METHODS: The association between timing of chemotherapy and reoperation rates (ROR) after lumpectomy was investigated for patients with stages 1-3 breast cancer in the National Cancer Database (NCDB) from 2010 to 2013 by multivariable logistic regression modeling. Then propensity score-matching was performed. RESULTS: The unadjusted ROR for 71,627 stages 1-3 patients was 11.4% for those who had NAC compared with 20.3% for those who had postoperative chemotherapy (p < 0.001) (odds ratio [OR] 0.53; 95% confidence interval [CI] 0.49-0.57; p < 0.001). The ORs for the reoperations performed for patients with stages 1, 2, and 3 cancers who received NAC were respectively 0.65 (95% CI 0.56-0.75), 0.50 (95% CI 0.45-0.56), and 0.27 (95% CI 0.19-0.38) The p values for all were lower than 0.001. CONCLUSION: For a population of patients receiving chemotherapy, the receipt of chemotherapy before instead of after surgery was associated with fewer reoperations after initial lumpectomy for breast cancer.

21-Gene recurrence score decreases receipt of chemotherapy in ER+ early-stage breast cancer: an analysis of the NCDB 2010-2013.

The purpose of this study was to determine if receipt of chemotherapy was associated with utilization of the 21-gene recurrence score assay (RS assay) or with recurrence score (RS) in eligible patients. Using the National Cancer Data Base (NCDB), we identified female patients eligible for RS assay based on National Comprehensive Cancer Network (NCCN) guidelines: age 18-70, ER-positive and HER2-negative early-stage breast cancer diagnosed during 2010-2013. We excluded patients not meeting testing guidelines. Inclusion required result of RS in patients who underwent RS assay and status for receipt of chemotherapy. Multivariable logistic regression models and propensity matched analysis were used to determine associations between RS assay and RS with receipt of chemotherapy. Among 129,765 patients who were eligible, 74,778 underwent RS assay and had results available. Of these, 59.5 % (44,505) had low-risk, 32.0 % (23,920) had intermediate-risk, and 8.5 % (6353) had high-risk RS. Patients with intermediate- and high-risk RS were more likely to receive chemotherapy [OR 12.9 (CI 12.2-13.6), p <0.001 and OR 87.2 (CI 79.6-95.6), p <0.0001], respectively. In both low- and intermediate-risk groups, increasing RS score was significantly associated with increasing odds of receiving chemotherapy [OR 1.10 (CI 1.09-1.12), p <0.0001 and OR 1.26 (CI 1.25-1.27), p <0.0001, respectively, for each point increase in RS]. Receipt of chemotherapy was more likely in patients who did not undergo RS assay compared to those who did, OR 1.21 (CI 1.175-1.249) p <0.0001. The utilization of RS assay and the RS were both strongly associated with chemotherapy receipt. Patients eligible for chemotherapy, based on NCCN criteria, were more likely to receive chemotherapy if they did not undergo RS assay or they had a high RS.

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting.

BACKGROUND: We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS: In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS: In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS: Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).

Effectiveness of a Survivorship Program: An Assessment of Patients With Breast Cancer in a Community Setting.

PURPOSE: This study assesses the effectiveness of a single institution's breast cancer survivorship program on patient perceptions, quality of life (QOL), and compliance with National Comprehensive Cancer Network (NCCN) guidelines for follow-up. METHODS: Sampled patients completed all their breast cancer treatment at a single tertiary center. Surveys designed to evaluate QOL were obtained, and retrospective medical record review was conducted to assess NCCN compliance. Survivorship clinic (SC) attendees and nonattendees were matched for age and disease stage for comparison of the outcomes (QOL, NCCN compliance, and overall effectiveness). RESULTS: SC patients (n = 63) tended to perceive their concerns in various categories to be addressed more adequately than did nonattendees (n = 54), with significant differences in the areas of practical concerns (P = .03) and late-term adverse effects (P = .03). There was a significant difference in compliance with three NCCN guidelines (history and physical every 3 to 6 months, annual mammography, and a pelvic examination if on tamoxifen) between survivorship attendees and nonattendees (P < .001, P = .02, and P < .001, respectively). Women who attended an SC used other survivorship support resources more often. CONCLUSION: Survivorship programs can be time and resource consuming, but our study is one of the first to show that a survivorship program effectively changes patient behavior in important ways. Patients who attended an SC were more likely to be compliant with NCCN-recommended follow-up and to use other survivorship resources and felt their concerns were better addressed. These measures can be used to help us improve our survivorship services and by other institutions to measure the quality and effectiveness of their programs.

Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study.

BACKGROUND: Estrogen receptor beta (ERß) is expressed by 50% to 80% of triple-negative breast cancers (TNBC). Agonism of ERß has antiproliferative effects in TNBC cells expressing ERß. This phase 2 study evaluated single-agent high-dose estradiol in patients with advanced TNBC. PATIENTS AND METHODS: Adult women with measurable advanced TNBC were treated with estradiol 10 mg oral 3 times daily provided continuously for 28-day cycles. A Simon optimal 2-stage design was used. The primary end point was objective response (OR). Secondary end points included progression-free survival (PFS), clinical benefit (CB), and safety. OR, CB, and PFS by ERß status were also examined. RESULTS: Seventeen evaluable women were enrolled. Median age was 58 years (range, 34-90 years); the median number of prior systemic therapies was 2 (range, 0-6). One patient had a confirmed partial response (OR rate, 5.9%) and remained on the study for > 24 weeks. Three patients had stable disease, with one lasting more than 16 weeks. ERß expression was detected in 77% (13 patients). The CB rate at 16 weeks was 15% (2 of 13) in ERß-positive patients and 0% (0 of 4) in ERß-negative patients (P = 1). PFS was poor (median, 1.9 months) and not statistically significantly different between ERß-positive versus -negative patients. No new adverse events from estradiol were identified. The study closed after the first stage as a result of limited responses in these unselected patients. CONCLUSION: In unselected TNBC, high-dose estradiol has limited efficacy. However, further evaluation of ERß selective agonists in TNBC selected by ERß expression may be warranted.

Institutional review of compliance with NCCN guidelines for breast cancer: lessons learned from real-time multidimensional synoptic reporting.

BACKGROUND: Variations exist in compliance with NCCN Guidelines. Prior reports of adherence to NCCN Guidelines contain limitations because of lack of contemporary review and incomplete listing of reasons for noncompliance. PURPOSE: To assess institutional compliance and assist national quality improvement strategies through identifying valid reasons for noncompliance. METHODS: Compliance with NCCN Guidelines was recorded prospectively using electronic synoptic templates for patients with newly diagnosed breast cancer treated at a single institution between January 2010 and December 2011. Compliance with NCCN Guidelines was recorded. The accuracy of real-time synoptic auditing methods compared with retrospective chart review and reasons for noncompliance was assessed. SAS 9.3 software was used for data analysis. RESULTS: Compliance with NCCN Guidelines among 395 patients was 94% for initial staging evaluation, 97% for surgery, 91% for chemotherapy, 89% for hormone therapy, 91% for radiation therapy, 85% for follow-up, and 100% for determination of estrogen receptor/progesterone receptor and HER2 status. Age, comorbidities, and stage influenced guideline compliance. The most common reasons for noncompliance were patient refusal, patient choice after shared decision-making, and overuse of testing. Synoptic templated reporting was accurate in 97% patients. CONCLUSIONS: High compliance with NCCN Guidelines was demonstrated. Reasons for noncompliance were identifiable. Compliance and nonadherence can be evaluated quickly with electronic synoptic reporting. This allows real-time action plans to address quality concerns and aids national risk adjustment for comparison and benchmarking.

Feasibility of 4 cycles of docetaxel and cyclophosphamide every 14 days as an adjuvant regimen for breast cancer: a Wisconsin Oncology Network study.

INTRODUCTION: Dose-dense therapies have had a major effect on reducing toxicity and improving outcomes in breast cancer. A combination of TC every 3 weeks has emerged as a common chemotherapy regimen used for treatment of node-negative or lower-risk node-positive breast cancer. We tested whether it is feasible to deliver TC on a dose-dense schedule, with therapy completed within 10 weeks. PATIENTS AND METHODS: We enrolled women with early stage breast cancer on a single-arm phase II study of adjuvant dose-dense TC through a regional oncology network. All women completed primary surgery before accrual, and subsequent therapy with TC was deemed appropriate by the treating physician. Planned treatment was docetaxel 75 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 2 weeks for 4 cycles with subcutaneous pegfilgrastim 6 mg administered 24 to 48 hours after the administration of each chemotherapy cycle. RESULTS: Of 42 women enrolled, 41 were evaluable using prespecified criteria. Of these, 37 (90.2%) completed therapy within 10 weeks and 34 (83%) completed therapy at 8 weeks without dose modification. Rates of neuropathy were similar to that reported previously. The rate of neutropenic fever was low (2.5%). Rash and plantar-palmar erythrodythesia were common and reached grade 3 in 4 subjects (9.8%). CONCLUSION: Dose-dense TC is feasible with tolerability profiles similar to standard TC and a low likelihood of neutropenic fever. This study supports further clinical development of this 8-week adjuvant chemotherapy regimen.

A phase II study of capecitabine and lapatinib in advanced refractory colorectal adenocarcinoma: A Wisconsin Oncology Network study.

BACKGROUND: Prognosis remains poor after progression on first-line chemotherapy for colorectal adenocarcinoma, and inactivation of the EGFR pathway with monoclonal antibodies is an effective treatment strategy in selected patients with metastatic disease. Lapatinib is an oral EGFR and HER-2 dual tyrosine kinase inhibitor that has not shown significant activity in metastatic colorectal cancer. However, lapatinib may act synergistically with capecitabine in anticancer effects. METHODS: This was an open-label, non-randomized phase II study of lapatinib 1,250 mg orally daily and capecitabine 2,000 mg/m(2) by mouth split into twice-daily dosing for 14 days of a 21 days cycle. Inclusion criteria included metastatic or locally advanced adenocarcinoma of the colon or rectum with progression by RECIST on or within six months of receiving a fluoridopyrimidine-, oxaliplatin- or irinotecan-containing regimen. Prior EGFR monoclonal antibody was permitted. K-ras testing was not routinely performed and was not a part of the study protocol. RESULTS: Twenty nine patients (16 M; 13 F) were enrolled in this study. There were no complete or partial responses. 41.4% of patients achieved stable disease as a best response. Median overall survival was 6.8 months, with a 1-year survival rate of 22%, and median progression-free survival was 2.1 months. The combination produced few grade 3 and no grade 4 toxicities. No grade 3 toxicity occurred in more than 10% of patients. CONCLUSIONS: Although capecitabine and lapatinib is well tolerated, it is not an effective regimen in patients with refractory colorectal adenocarcinoma.

A community breast center report card determined by participation in the national quality measures for breast centers program.

Measurement of quality indicators and peer comparison has been demonstrated to improve quality of care. The goal of this study was to determine whether a community breast center, in collaboration with the National Consortium of Breast Centers (NCBC), could voluntarily audit the quality of breast cancer care, confidentially transmit quality information to the NCBC, and receive peer performance comparisons. Quality indicator metrics from consecutive breast cancer patients undergoing care at a community interdisciplinary breast center were entered into a prospective database of quality measures that were defined by the NCBC. Retrospective review of patients from 2004 to 2006 was performed and subsequent quality indicator data was submitted electronically to the NCBC National Quality Measures for Breast Centers (NQMBC(TM) ) program. The percentage of new cancer diagnoses made by needle biopsy techniques was 94%, 95% and 96% from 2004 to 2006. Sentinel lymph node utilization in eligible patients was 93%, 96% and 91% from 2004 to 2006 and the immediate intraoperative pathologic frozen section false negative rate of the sentinel lymph node was 6.5%, 4.7% and 4%. Chart documentation of "patient participation in shared decision making for breast conserving therapy versus mastectomy" improved from 74% to 99% (p<0.05) from 2004 to 2006. Adjuvant systemic treatment for stage 2 breast cancer occurred in 76%, 89% and 77% of patients from 2004 to 2006. Neutropenia requiring hospital admission occurred in no patients in 2004 but in 4.8% and 2.9% in 2005 and 2006. The re-excision lumpectomy rates for stage 0, 1, 2, and 3 breast cancer patients from 2004 to 2006 was 14.2%, 22% and 24.8%. Quality indicator data was submitted to the NQMBC(TM) with successful confidential receipt of peer performance comparisons. Voluntary interdisciplinary institutional audits of breast cancer quality can be successfully submitted to the NQMBC(TM) with confidential peer performance comparison.

A breast center review of compliance with National Comprehensive Cancer Network Breast Cancer guidelines.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guideline compliance for breast cancer was determined in a breast center. METHODS: A retrospective study of 200 new breast cancer patients seen in 2004 was performed. RESULTS: NCCN guideline compliance rates for preoperative evaluation, breast surgery, lymph node surgery, radiation treatment, and systemic adjuvant therapy were 87%, 97%, 97%, 77%, and 63%, respectively. The most common reasons for noncompliance were partial breast radiation, no radiation, limited life expectancy, and patient choice to defer systemic treatment. CONCLUSIONS: The investigation of quality of breast cancer care requires measurement of compliance and reasons for noncompliance with established guidelines. A review that focuses only on percentage compliance has the potential to penalize institutions that (1) practice informed consent detailing absolute risks of survival with and without systemic therapy, (2) practice evidence-based medicine before the standardized guideline is changed to reflect it, and (3) serve populations with limited life expectancy.

Phase II trial of weekly paclitaxel in patients with advanced melanoma.

New therapies are needed to improve the prognosis of patients with metastatic melanoma. This study evaluates the safety and efficacy of weekly paclitaxel in patients with metastatic melanoma. Patients received paclitaxel at 80 mg/m over 1 h, weekly for 3 weeks, followed by a 1-week rest period. Disease status was assessed every other cycle. Treatment was continued until patients experienced either disease progression or unacceptable toxicity. Twenty-seven patients were enrolled in this phase II clinical trial. Of these patients, two were subsequently determined to be ineligible. All patients, however, were considered to be evaluable for toxicity and all patients were included for response assessment in an intention-to-treat analysis. Patients received paclitaxel for a median of two cycles (range, <1-8). None of the 27 patients showed a response to treatment. Eight patients had stable disease. The median progression-free survival was 1.8 months (95% confidence interval, 1.7-2.5 months) and the median survival was 7.6 months (95% confidence interval, 4.7-9.7 months). The most common grade 3 toxicity was neutropenia (four patients) and one patient had grade 4 neutropenia. Other treatment-related grade 3 toxicities included hypersensitivity reaction (one patient) and diarrhoea (one patient). Of note, five patients had peripheral neuropathy; however, in each case, the neuropathy was only grade 1. Weekly paclitaxel is relatively well tolerated and can maintain disease stability for some metastatic melanoma patients. Unfortunately, the anti-tumour activity of this single-agent therapy is low and additional treatment innovations are needed.