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Objective: The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany., Methods: A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually., Results: The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care., Limitations: Country-specific data on the risk of distant recurrence and quality-of-life were not available., Conclusions: Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current standard of care women with ER+, HER2- early-stage breast cancer.

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

Purpose: To investigate the effect of adjuvant sequential tamoxifen after chemotherapy in postmenopausal patients with hormone receptor-negative breast cancer., Methods: Patients were randomly assigned to oral tamoxifen (30 mg daily for 5 years; n = 421) or no additional treatment (n = 408) after risk-adapted polychemotherapy consisting of three 28-day cycles of CMF (cyclophosphamide, 500 mg/m(2), methotrexate, 40 mg/m(2), and fluorouracil, 600 mg/m(2)) in patients with negative or one to three positive lymph nodes and four 21-day cycles of epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) followed by three cycles of CMF in patients with four to nine positive lymph nodes., Results: Thirty-six percent of the patients included were older than 60 years, 63% were node negative, 13% had four to nine positive nodes, 55% had tumor grade 3, and 41% received breast-preserving surgery. At 5.3 years' median follow-up, the first event of failure (recurrence, secondary tumor, or death) had occurred in 123 patients in the tamoxifen group and 107 patients of the control group. Event-free survival rates after 5 years were 70.3% (95% CI, 65.5% to 75.0%) and 72.8% (95% CI, 68.2% to 77.5%) for the tamoxifen and control groups, respectively. The estimated hazard ratio of tamoxifen versus control was 1.13 (95% CI, 0.87 to 1.48; P = .34), which gives no indication of an additional benefit of tamoxifen in these patients., Conclusion: This study contributes substantially to finalization of the presently emerging evidence that tamoxifen does not benefit women with receptor-negative breast cancer after chemotherapy.

The management of breast cancer care poses very high expectations on implementing the treatment recommendations and guidelines for diagnostic procedures into routine treatment. Most recently a majority of these tasks has been transferred to the responsibilities of the breast centers being established all over Germany these days. Guidelines on treatment and diagnostic procedures and minimal invasive techniques have therefore been discussed among 1 300 colleagues and experts at the Duesseldorfer Symposium in June 2004.

Preoperative chemotherapy represents the standard procedure in inflammatory breast cancer. However, only recently it could be demonstrated that preoperative chemotherapy is beneficial even for patients with operable primary breast cancer. The number of breast conserving surgeries could be increased significantly. Furthermore this in vivo chemosensitivity assay can provide important prognostic as well as predictivy informations. Preoperative chemotherapy is not associated with an increased risk for the patients as outcome is similar to patients with conventional adjuvant treatment. We investigated new regimens to improve this type of chemotherapy and reached a remission rate of 93% with a combination of adriamycin and docetaxel (ADoc). A randomized study (GEPARDO-study) comparing ADoc with ADoc + tamoxifen has recently been started in Germany by the German Adjuvant Breast Cancer Study Group (GABG).