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.

Identification and validation of an anthracycline/cyclophosphamide-based chemotherapy response assay in breast cancer.

BACKGROUND: There is no method routinely used to predict response to anthracycline and cyclophosphamide-based chemotherapy in the clinic; therefore patients often receive treatment for breast cancer with no benefit. Loss of the Fanconi anemia/BRCA (FA/BRCA) DNA damage response (DDR) pathway occurs in approximately 25% of breast cancer patients through several mechanisms and results in sensitization to DNA-damaging agents. The aim of this study was to develop an assay to detect DDR-deficient tumors associated with loss of the FA/BRCA pathway, for the purpose of treatment selection. METHODS: DNA microarray data from 21 FA patients and 11 control subjects were analyzed to identify genetic processes associated with a deficiency in DDR. Unsupervised hierarchical clustering was then performed using 60 BRCA1/2 mutant and 47 sporadic tumor samples, and a molecular subgroup was identified that was defined by the molecular processes represented within FA patients. A 44-gene microarray-based assay (the DDR deficiency assay) was developed to prospectively identify this subgroup from formalin-fixed, paraffin-embedded samples. All statistical tests were two-sided. RESULTS: In a publicly available independent cohort of 203 patients, the assay predicted complete pathologic response vs residual disease after neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline, and cyclophosphamide) with an odds ratio of 3.96 (95% confidence interval [Cl] =1.67 to 9.41; P = .002). In a new independent cohort of 191 breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, a positive assay result predicted 5-year relapse-free survival with a hazard ratio of 0.37 (95% Cl = 0.15 to 0.88; P = .03) compared with the assay negative population. CONCLUSIONS: A formalin-fixed, paraffin-embedded tissue-based assay has been developed and independently validated as a predictor of response and prognosis after anthracycline/cyclophosphamide-based chemotherapy in the neoadjuvant and adjuvant settings. These findings warrant further validation in a prospective clinical study.