The International Consensus Conference on the treatment of primary breast cancer takes place every two years in St. Gallen, Switzerland. The panel in St. Gallen is composed of international experts from different countries. From a German perspective, it seems reasonable to interpret the voting results in the light of AGO-recommendations and S3-guidelines for everyday practice in Germany. Consequently, a team of eight breast cancer experts, of whom two are members of the international St. Gallen panel, commented on the voting results of the St. Gallen Consensus Conference (2013). The main topics at this year's St. Gallen conference were surgical issues of the breast and axilla, radio-therapeutic and systemic treatment options, and the clinical relevance of tumour biology. The clinical utility of multigene assays for supporting individual treatment decisions was also intensively discussed.
St. Gallen Consensus; Early breast cancer; Adjuvant therapy; Multigene signatures; Targeted therapy
Elderly breast cancer patients are underrepresented in clinical trials and this leads to a lack of knowledge regarding the tolerance and side effects of modern chemotherapy regimens, especially in dose-dense (dd) or dose-intensified combination.
Patients and Methods
In this analysis, data from 4 German, randomized (neo-)adjuvant trials, including anthracycline-based chemotherapy, were evaluated for toxicity, compliance and feasibility. Patients were grouped according to age.
Of the 4,775 patients, 73.6% were < 60 years, 15.8% were 60–64 years and 10.6% were > 64 years. The patients’ compliance decreased with increasing age, the rate of therapy discontinuations was 10.3%; 16.0% were > 64 years old (p < 0.001). The rate of dose reductions also increased with increasing age in the docetaxel/doxorubicin/cyclophosphamide (TAC) (p overall = 0.02) and 5-fluorouracil/epirubicin-cyclophosphamide (FE120C) (p overall < 0.001) treatment groups. Neutropenia grade 3 + 4 in patients of > 64 years was 77% in FE120C- compared to 55% in TAC-treated patients (with primary granulocyte colony-stimulating factors (G-CSFs)). The incidence of febrile neutropenia (FN) was lowest in the regimens without additional taxanes. FN in patients aged > 64 years was lower in the FE120C- than in TAC-and dd-doxorubicin/docetaxel-treated groups.
The range and intensity of toxicity increased with age. Neutropenia did not increase significantly in the dd groups; the highest rate was seen in FE120C-treated patients. FE120C without G-CSFs is not an option in patients older than 64 years.
Elderly; Chemotherapy; Side effect; Tolerability; Breast cancer
The goal of this population-based study was to determine the impact of post-mastectomy radiation therapy on long-term overall survival (OS) of male patients with breast cancer.
Patients and Methods
We investigated 20-year OS rates of 664 patients diagnosed with primary stage I–III breast cancer in former East Germany between 1970 and 1989. Patients had a radical mastectomy with axillary lymph node dissection without systemic adjuvant therapy.
Median follow-up time was 26.2 years (range 19–38 years). 52.4% of the patients had post-mastectomy radiotherapy. Radiotherapy showed different effects in each stage group after 20 years. Whereas there was an OS trend for radiotherapy to harm patients with stage I disease (hazard ratio (HR) 1.45; 95% confidence interval (CI) 0.98–2.15; p = 0.065), radiotherapy showed no benefit in patients with stage II disease (HR 0.82; 95% CI 0.62–1.1; p = 0.15). There was a significant survival benefit for patients with stage III disease receiving radiotherapy (HR 0.60; 95% CI 0.41–0.88; p = 0.008).
Post-mastectomy radiotherapy is associated with longer OS in male patients with stage III breast cancer. Male breast cancer patients at stages I and II do not seem to benefit from radiotherapy, but obsolete irradiation techniques might explain adverse long-term effects in earlier stages.
Male breast cancer; Adjuvant radiotherapy; Adjuvant Therapy; Overall survival
A group of German breast cancer experts (medical oncologists and gynaecologists) reviewed and commented on the results of the first international ‘Advanced Breast Cancer First Consensus Conference’ (ABC1) for the diagnosis and treatment of advanced breast cancer. The ABC1 Conference is an initiative of the European School of Oncology (ESO) Metastatic Breast Cancer Task Force in cooperation with the EBCC (European Breast Cancer Conference), ESMO (European Society of Medical Oncology) and the American JNCI (Journal of the National Cancer Institute). The main focus of the ABC1 Conference was metastatic breast cancer (stage IV). The ABC1 consensus is based on the vote of 33 breast cancer experts from different countries and has been specified as a guideline for therapeutic practice by the German expert group. It is the objective of the ABC1 consensus as well as of the German comments to provide an internationally standardized and evidence-based foundation for qualified decision-making in the treatment of metastatic breast cancer.
ABC1-consensus; Metastatic breast cancer, diagnosis and staging, treatment; Tumor markers; Metastases, biopsy; Chemotherapy; Endocrine therapy; Anti-HER2-targeted therapy; Palliative care
Since the introduction of trastuzumab into the treatment of Her-2/neu-positive metastatic breast cancer, cases of long-term survival have become more frequent. Even after tumor progression, trastuzumab seems to retain its antitumor activity which is potentiated by the combination with a chemotherapeutic agent.
We are reporting about the unusual clinical course of a young patient with Her-2/neu-positive breast cancer, who experienced progression of pulmonary and bone metastases under treatment with trastuzumab. Upon progression, a combination therapy with capecitabine/trastuzumab was initiated, and a partial remission was achieved which has continued for over 4 years.
This unusual clinical course shows that continuing trastuzumab-based therapy beyond progression is a safe, effective, and well-tolerated option which can induce long-term remissions in some patients with Her-2/neu-positive metastatic breast cancer.
Breast cancer; Metastasized; Capecitabine; Trastuzumab
The combination of bendamustine (B) and paclitaxel (P) as anthracycline-free treatment option in patients with advanced breast cancer has been evaluated in the previous RiTa I trial. The regimen of weekly B 70 mg/m2 and P 90 mg/m2 with a pause every 4th week was established as an effective regimen with low toxicity. The aim of the present RiTa II study was to investigate the potential of BP as anthracycline-free combination therapy. The primary objective was to determine the progression-free survival (PFS); secondary endpoints were safety, tolerability, overall response rate (ORR) and overall survival (OS). 26 patients were available, 15 received BP as first-line, 11 as beyond first-line treatment. 27% patients had triple-negative breast cancer (TNBC). Median PFS and OS were 7.3 months (95% confidence interval (CI): 5.5–10.9) and 14.9 months (95% CI: 9.9–22.9), respectively. The 1-year PFS rate was 20.3% and the 1-year OS rate 71.2%. The ORR was 42.3%, including 4 complete and 7 partial remissions. TNBC patients reached an ORR of 71.4%. Anthracycline-pretreated patients showed an ORR of 43.8%, confirming bendamustine's lack of cross-resistance to anthracycline agents. BP represents a favorable option with moderate toxicity in pretreated metastatic breast cancer and offers a possibility for application in anthracycline-pretreated and TNBC patients.
Bendamustine; Paclitaxel; Breast cancer, metastatic; Efficacy; Combination therapy; First-line chemotherapy
Neoadjuvant chemotherapy is the standard of care for patients with large, inoperable tumors or inflammatory breast cancer, but it is also increasingly considered for women with operable disease. Several randomized trials have demonstrated that anthracycline- and taxane-containing regimens in operable breast cancer were equally effective in terms of disease-free or overall survival regardless of whether they were administered postoperatively or preoperatively. Further neoadjuvant treatment allows for a higher rate of breast conserving surgery. Tumor responses in terms of pathologic complete remission after short-term chemotherapy will probably only serve as a surrogate marker for long-term outcome in some molecular breast cancer subtypes like the triple-negative, HER2-positive, and some luminal B subsets. Recent trials showed that in HER2-positive disease pCR rates were as high as 70% when 2 HER2-targeted agents were added to chemotherapy.
Neoadjuvant chemotherapy; Pathologic complete remission; Molecular subtypes; HER2-positive breast cancer
About 10-25% of breast cancer patients achieve a pathologically confirmed complete response after neoadjuvant chemotherapy. Tissue samples of pretreatment core biopsies are a valuable resource for translational research aiming towards predictive biomarkers for selecting patients who are likely to benefit from neoadjuvant therapy. The German Breast Group (GBG) and the AGO-B Group (AGO = Working Group Gynecological Oncology) have extensive experience in conducting neoadjuvant clinical trials. Technologies as immunohistochemistry on tissue microarrays and standardized reverse transcription-polymerase chain reaction (RT-PCR) approaches on formalin-fixed paraffin-embedded samples allow high-throughput investigation of protein and mRNA biomarkers. With these approaches, we could demonstrate that molecular tumor subtypes and immunological infiltrates are valuable and independent predictors of therapy response. New biomarkers such as poly(ADPribose) polymerase (PARP) might be useful for the prediction of response to conventional and new targeted therapies. This review summarizes current research projects focusing on biomarker discovery in the neoadjuvant setting.
Neoadjuvant; Chemotherapy; Breast cancer Lymphocytes; PARP
Background: Docetaxel and paclitaxel are among the most active substances for the treatment of breast cancer. As both drugs are used today in adjuvant regimens, efficacy data from pivotal trials in the metastatic setting in taxane-naive populations cannot reliably be used as references. Patients and Methods: The Taxane Re-Challenge Cohort Study identified participants from 6 prospective (neo-)adjuvant taxane-based studies with recurrent disease and collected data on their subsequent treatment. Out of 381 recurrent patients, 106 (27.8%) were re-challenged with a taxane-based treatment as first- or later-line therapy for recurrent disease. Results: Taxanes were used as first-line therapy in 74 patients and showed a response rate of 48.6% (including complete responses in 27.0%). The response rate was dependent on the disease-free interval (<1 year: 34.8%; 1-2 years: 42.9%; >2 years: 63.3%; p = 0.04) and visceral metastasis (present: 62.5%; not present 32.4%; p = 0.01). Patients without visceral metastasis and with a disease-free interval of >2 years achieved the longest overall survival. Hormone and HER2 receptor status were not predictive; however, triple-negative tumors responded in 50.0%. The overall response rate of later-line taxane-based treatment was 28.2%. Conclusion: Re-challenging taxanes appears to be effective and therefore represents a reasonable option in this population.
Docetaxel; Paclitaxel; Adjuvant; Recurrent breast cancer
A German working group of 23 breast cancer experts discussed the results from the vote at this year's St. Gallen Consensus Conference on Primary Therapy for Early Breast Cancer (March 11–14, 2009) and came up with some concrete recommendations for day-to-day therapeutic decisions in Germany. Due the fact that the concept of the St. Gallen Consensus Conference merely allows for a minimal consensus, the objective of the working group was to provide practice-related recommendations for day-to-day clinical decisions in Germany. One area of emphasis at St. Gallen was tumor biology as a starting point for reaching individual therapeutic decisions. Intensive discussion was necessary with respect to the clinical relevance of predictive and prognostic factors. A new addition to the area of systemic therapy was a first-ever discussion of the adjuvant administration of bisphosponates and the fact that therapy with trastuzumab in HER2 overexpressing breast cancer has been defined as the standard for neoadjuvant therapy. The value of taxanes as a component of (neo)adjuvant chemotherapy as well as the value of aromatase inhibitors for the endocrine adjuvant treatment of postmenopausal patients were affirmed.
The goal of treatment for patients with advanced breast cancer is to prolong survival, control symptoms, and reduce disease-related complications. Despite the introduction of many cytotoxic agents during the past decade, only modest improvement in survival in metastatic breast cancer has been achieved. In order to improve this situation, new cytotoxic drugs as well as molecule-targeted agents are now under investigation. Bendamustine is a bifunctional alkylating agent with cytotoxic activity against several types of solid tumors. In the search for new anthracycline-free combinations, taxanes and alkylating agents might be worth investigating, in order to reduce cardiac toxicity. In this article, we reviewed the latest information regarding antitumor activity, toxicity, pharmacokinetics, and clinical application of bendamustine as a cytotoxic agent in metastatic breast cancer.
Bendamustine; First-line chemotherapy; Metastatic breast cancer
The Organgruppe Mamma of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) performed a nationwide 3-phase analysis of the structure of care and standard of therapy given to patients with breast cancer from 2002 (4th quarter) to 2004 (4th quarter). The extent to which national and international treatment recommendations are implemented in routine clinical practice had so far not been evaluated in an interdisciplinary approach. No reliable data on the pattern of care of these patients have been published in Germany before.
Patients and Methods
The project included early breast cancer in the adjuvant and neoadjuvant setting as well as metastatic disease. We present the results of phase III of the AGO analysis, which are based on a survey conducted by the Organkommission Mamma in the 4th quarter of 2004.
Evaluation of the data reveals that treatment based on the guidelines is now being implemented very reliably in certain sectors. This is of particular relevance to the pattern of adjuvant treatment in early breast cancer. In contrast, in metastatic breast cancer (MBC), the complexity of the interdisciplinary treatment approach is complicating this kind of straightforward analysis.
The present analysis conducted by the AGO was the first attempt to analyse the treatment provided in patients presenting with MBC in a systematic fashion. The fundamental problem remains, irrespective of the stage of the tumour, that too few patients are treated in randomised clinical trials. The mission set by the AGO-Organkommission Mamma is the longitudinal observation of the therapy practices for breast cancer on the basis of the observations discussed here, which should ultimately benefit the optimisation of therapy quality in Germany.
Breast cancer treatment; Healthcare research; Adjuvant treatment; Breast cancer, metastatic; Guideline adherence