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BACKGROUND: The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. METHODS: In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. RESULTS: A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. CONCLUSIONS: Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).

The objectives of this study were to examine the patterns of use for adjuvant therapy and the changes in surgical practice for patients with early stage breast cancer and to describe how recent large clinical trial results impacted the patterns of care at The University of Texas M. D. Anderson Cancer Center (MDACC).The study included 5486 women who were diagnosed with stage I through IIIA breast cancer between 1997 and 2004 and received their treatment at MDACC. A chi-square trend test and multivariate logistic regression model were used to assess changes in treatment patterns over time.Among lymph node-positive patients, the use of anthracycline plus taxane chemotherapy increased from 17% in 1997 to 81% in 2004 (P.001). Meanwhile, the use of anthracyclines without taxanes dropped from 76% to 20% (P.001) between 1997 and 2000. For postmenopausal patients who received endocrine therapy, the use of tamoxifen was replaced increasingly by the use of aromatase inhibitors (from 100% on tamoxifen in 1997 to 14% in 2004; P.001). The percentage of women who underwent initial sentinel lymph node biopsy increased significantly during the period from 1997 to 2004 (from 1.8% to 69.7%, respectively, among patients who underwent mastectomy; and from 18.1% to 87.1%, respectively, among patients who underwent breast-conserving surgery; P.001).The results from this study suggested that key findings from adjuvant therapy and surgical procedures from large clinical trials often prompt immediate changes in the patient care practices of research hospitals like MDACC.

The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.

Despite trials of mammography and widespread use, optimal screening policy is controversial.To evaluate U.S. breast cancer screening strategies.6 models using common data elements.National data on age-specific incidence, competing mortality, mammography characteristics, and treatment effects.A contemporary population cohort.Lifetime.Societal.20 screening strategies with varying initiation and cessation ages applied annually or biennially.Number of mammograms, reduction in deaths from breast cancer or life-years gained (vs. no screening), false-positive results, unnecessary biopsies, and overdiagnosis.The 6 models produced consistent rankings of screening strategies. Screening biennially maintained an average of 81% (range across strategies and models, 67% to 99%) of the benefit of annual screening with almost half the number of false-positive results. Screening biennially from ages 50 to 69 years achieved a median 16.5% (range, 15% to 23%) reduction in breast cancer deaths versus no screening. Initiating biennial screening at age 40 years (vs. 50 years) reduced mortality by an additional 3% (range, 1% to 6%), consumed more resources, and yielded more false-positive results. Biennial screening after age 69 years yielded some additional mortality reduction in all models, but overdiagnosis increased most substantially at older ages.Varying test sensitivity or treatment patterns did not change conclusions.Results do not include morbidity from false-positive results, patient knowledge of earlier diagnosis, or unnecessary treatment.Biennial screening achieves most of the benefit of annual screening with less harm. Decisions about the best strategy depend on program and individual objectives and the weight placed on benefits, harms, and resource considerations.National Cancer Institute.