Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial.

Purpose: MINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment (R-C) compared docetaxel-capecitabine with an anthracycline-based regimen.

Patients And Methods: R-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m intravenously plus oral capecitabine 825 mg/m two times per day for 14 days (DC) every 3 weeks for 6 cycles.

Association Between 21-Gene Assay Recurrence Score and Locoregional Recurrence Rates in Patients With Node-Positive Breast Cancer.

Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain.

Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone.

Design, Setting, And Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy.

Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.

Background: The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known.

Methods: We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade.

Germline Genetic Variants in GATA3 and Breast Cancer Treatment Outcomes in SWOG S8897 Trial and the Pathways Study.

Introduction: GATA3 is a critical transcription factor in maintaining the differentiated state of luminal mammary epithelial cells. We sought to determine the prognostic and predictive roles of GATA3 genotypes for breast cancer.

Patients And Methods: Twelve single nucleotide polymorphisms (SNPs) were genotyped in 2 breast cancer cohorts, including the SWOG S8897 trial where patients were treated with adjuvant chemotherapy (CAF [cyclophosphamide, doxorubicin, 5-fluorouracil] vs.

Communicating Risks of Adjuvant Chemotherapy for Breast Cancer: Getting Beyond the Laundry List.

Purpose: According to the Institute of Medicine, high-quality cancer care should include effective communication between clinicians and patients about the risks and benefits, expected response, and impact on quality of life of a recommended therapy. In the delivery of oncology care, the barriers to and facilitators of communication about potential long-term and late effects, post-treatment expectations, and transition to survivorship care have not been fully defined.

Patients And Methods: We collected qualitative data through semistructured interviews with medical oncologists and focus groups with breast cancer survivors and applied the Theoretical Domains Framework to systematically analyze and identify the factors that may influence oncologists' communication with patients with breast cancer about the long-term and late effects of adjuvant therapy.

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.

Background: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score.

Methods: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone.

Accuracy of the online prognostication tools PREDICT and Adjuvant! for early-stage breast cancer patients younger than 50 years.

Importance: Online prognostication tools such as PREDICT and Adjuvant! are increasingly used in clinical practice by oncologists to inform patients and guide treatment decisions about adjuvant systemic therapy. However, their validity for young breast cancer patients is debated.

Objective: To assess first, the prognostic accuracy of PREDICT's and Adjuvant! 10-year all-cause mortality, and second, its breast cancer-specific mortality estimates, in a large cohort of breast cancer patients diagnosed <50 years.

Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.

Background: Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker.

Methods: We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.

The EORTC 10041/BIG 03-04 MINDACT trial is feasible: results of the pilot phase.

Background: The MINDACT (Microarray In Node-negative and 1-3 node positive Disease may Avoid ChemoTherapy) trial investigates the clinical utility of the 70-gene profile (MammaPrint) for the selection of breast cancer patients for adjuvant chemotherapy (CT) together with standard clinicopathological criteria. We present the results of the pilot phase consisting of first 800 patients included.

Methods: MINDACT has enrolled 6600 patients, classified into high or low risk by MammaPrint and clinicopathological risk through Adjuvant! Online.

Cancer and Leukemia Group B Pathology Committee guidelines for tissue microarray construction representing multicenter prospective clinical trial tissues.

Practice-changing evidence requires confirmation, preferably in multi-institutional clinical trials. The collection of tissue within such trials has enabled biomarker studies and evaluation of companion diagnostic tests. Tissue microarrays (TMAs) have become a standard approach in many cooperative oncology groups.

Independent prognostic value of screen detection in invasive breast cancer.

Background: Mammographic screening has led to a proportional shift toward earlier-stage breast cancers at presentation. We assessed whether the method of detection provides prognostic information above and beyond standard prognostic factors and investigated the accuracy of predicted overall and breast cancer-specific survival by the computer tool Adjuvant! among patients with screen-detected, interval, and nonscreening-related carcinomas.

Methods: We studied 2592 patients with invasive breast cancer who were treated at the Netherlands Cancer Institute from January 1, 1990, through December 31, 2000.

Gene polymorphisms in cyclophosphamide metabolism pathway,treatment-related toxicity, and disease-free survival in SWOG 8897 clinical trial for breast cancer.

Purpose: There are no established genetic markers for prediction of outcomes after cyclophosphamide (CP)-containing adjuvant therapy for breast cancer. In an ancillary study to a SWOG (Southwest Oncology Group) trial (S8897), we investigated functional polymorphisms in 4 genes in CP pharmacokinetic pathways in relation to hematologic toxicity and disease-free survival (DFS).

Experimental Design: Germline DNA was available from 458 women who were at high risk of relapse and was randomized to CAF (CP, intravenous doxorubicin, and 5-fluorouracil) versus CMF (CP, intravenous methotrexate, and 5-fluorouracil) ± tamoxifen, and from 874 women who had a presumed favorable prognosis and did not receive adjuvant therapy.

Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women.

Context: In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.

The lack, need, and opportunities for decision-making and informational tools to educate primary-care physicians and women about breast cancer chemoprevention.

This perspective on Vogel et al. (beginning on page 696 in this issue of the journal) examines tamoxifen and raloxifene prescription patterns and why these agents are little used for breast cancer prevention despite their effectiveness in definitive trials, Food and Drug Administration approval, and American Society of Clinical Oncology Guidelines Committee endorsement for this purpose. The complexity of weighing the positive and negative aspects of the drugs and estimating net benefit is discussed, as is the need for informational resources such as interactive Internet-based tools to allow better individualized decisions about the options for chemoprevention.

Manganese superoxide dismutase polymorphism, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer.

To date, the few studies of associations between a functional polymorphism in the oxidative stress-related gene manganese superoxide dismutase (SOD2) and breast cancer survival have been inconsistent. In a homogeneous patient population from a large cooperative group trial Southwest Oncology Group (SWOG) 8897, we evaluated this polymorphism in relation to both treatment-related toxicity and disease-free survival (DFS). Among 458 women who received cyclophosphamide-containing adjuvant chemotherapy, those with variant C alleles, related to higher antioxidant activity, experienced less grade 3-4 neutropenia (OR = 0.

Ki67 in breast cancer: prognostic and predictive potential.

The leading parameters that define treatment recommendations in early breast cancer are oestrogen-receptor, progesterone-receptor, and human epidermal growth-factor status. Although some pathologists report Ki67 in addition to other biological markers, the existing guidelines of the American Society of Clinical Oncology do not include Ki67 in the list of required routine biological markers. The advent of new genetic tests has emphasised the role of proliferative genes, including Ki67, as prognostic and predictive markers.

Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.

Background: The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence.

Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial.

Background: Tamoxifen is standard adjuvant treatment for postmenopausal women with hormone-receptor-positive breast cancer. We assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy.

Methods: We undertook a phase 3, parallel, randomised trial (SWOG-8814, INT-0100) in postmenopausal women with hormone-receptor-positive, node-positive breast cancer to test two major objectives: whether the primary outcome, disease-free survival, was longer with cyclophosphamide, doxorubicin, and fluorouracil (CAF) given every 4 weeks for six cycles plus 5 years of daily tamoxifen than with tamoxifen alone; and whether disease-free survival was longer with CAF followed by tamoxifen (CAF-T) than with CAF plus concurrent tamoxifen (CAFT).

NCCN Task Force Report: Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry.

The NCCN Task Force on Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry was convened to critically evaluate the extent to which the presence of the estrogen receptor (ER) and progesterone receptor (PgR) biomarkers in breast cancer serve as prognostic and predictive factors in the adjuvant and metastatic settings, and the ability of immunohistochemical (IHC) detection of ER and PgR to provide an accurate assessment of the expression of these biomarkers in breast cancer tumor tissue. The task force is a multidisciplinary panel of 13 experts in breast cancer who are affiliated with NCCN member institutions and represent the disciplines of pathology, medical oncology, radiation oncology, surgical oncology, and biostatistics. The main overall conclusions of the task force are ER is a strong predictor of response to endocrine therapy; ER status of all samples of invasive breast cancer or ductal carcinoma in situ (DCIS) should be evaluated by IHC; IHC measurements of PgR, although not as important clinically as ER, can provide useful information and should also be performed on all samples of invasive breast cancer or DCIS; IHC is the main testing strategy for evaluating ER and PgR in breast cancer and priority should be given to improve the quality of IHC testing methodologies; all laboratories performing IHC assays of ER and PgR should undertake formal validation studies to show both technical and clinical validation of the assay in use; and all laboratories performing IHC assays of hormone receptors in breast cancer should follow additional quality control and assurance measures as outlined in the upcoming guidelines from the American Society of Clinical Oncology and College of American Pathologists.

Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms.

Background: Despite trials of mammography and widespread use, optimal screening policy is controversial.

Objective: To evaluate U.S.

High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller.

Purpose: To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer.

Methods: We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.