A better understanding of tumor biology has led to the development of a number of antibody-based targeted therapies in breast cancer. Several of these newer agents, such as trastuzumab and bevacizumab have demonstrated clinical activity and have improved the treatment of patients with metastatic breast cancer (MBC). Trastuzumab is a monoclonal antibody that binds to the extracellular domain of the HER2 receptor. The addition of trastuzumab to chemotherapy and also to endocrine therapy has enhanced efficacy of treatment. New antibody-based strategies directed against HER2 are under development. These new approaches include pertuzumab, an antibody with a different binding epitope that inhibits dimerization of HER2 with other members of the HER receptor family and TDM1, a trastuzumab-based antibody chemotherapeutic conjugate. Another approach to the treatment of solid tumors is inhibition of angiogenesis. The anti-VEGF antibody bevacizumab has been approved for treatment of MBC. Although the mechanism of action is still under investigation, bevacizumab is tested in other clinical settings such as adjuvant therapy, maintenance therapy, and in combination with both chemotherapy and other targeted agents. In this review, we will summarize the most important studies on trastuzumab and bevacizumab, and describe new antibodies currently under clinical development.
Breast cancer; Metastasis; Antibody; Therapy
Metastatic breast cancer (MBC) is usually not curable, and the primary goals of treatment are thus to control disease and symptoms, maintain quality of life, and prolong life while minimizing toxicity. Chemotherapy is still an important treatment option in MBC, and the decision whether polychemotherapy is preferable to sequential monochemotherapy is under debate. Data are quite consistent in that response rates and time to progression are significantly increased with combination chemotherapy compared to the use of a single agent in MBC patients. Data regarding overall survival with polychemotherapy are not conclusive; however, frequently this approach was associated with increased treatment toxicity and decreased quality of life. Nonetheless, in patients with symptomatic or acute, life-threatening disease, where maximum and quick tumor remission is important, polychemotherapy should be the preferred approach. Furthermore, since some of the newer combination regimens seem to increase toxicity only slightly and substantially prolong time to progression, this approach may also be an option in patients without symptomatic disease.
Breast cancer; Metastasis; Polychemotherapy
Preclinical and clinical trials suggest that tyrosine kinase inhibitors (TKI) could supplement current therapies in metastatic breast cancer (MBC). HER-2 inhibition is still a main focus. Numerous agents targeting the epidermal growth factor receptors EGFR and HER-2 are currently tested after previous trastuzumab treatment. Lapatinib targets HER-2 and EGFR. As monotherapy, clinical activity was low. Combined with cytotoxic agents, lapatinib showed good activity (overall response rate (ORR) 24-27%) and moderate toxicity. Neratinib, a pan-ErbB TKI, showed an ORR of 26%. Neratinib combined with trastzumab was well tolerated and active (ORR = 27%). After bevacizumab's proof-of-concept studies, anti-angiogenesis remains of importance. Sunitinib inhibits the vascular endothelial growth factor receptor (VEGFR), the platelet-derived growth factor receptor (PDGFR), c-kit and the colony-stimulating factor 1 (CSF-1) receptor. Monotherapy is tolerated and moderately active in MBC. Combination trials are ongoing. Toxicities of docetaxel ± sunitinib were manageable (ORR 72.2%). Pazopanib targets VEGFR, PDGFR and c-kit. Pazopanib ± lapatinib was superior in combination (progression-free survival (PFS) = 27% vs. 19%). Axitinib has similar targets. Combined with docetaxel, it was superior compared to placebo (ORR 40% vs. 23%), with manageable toxicity. Imatinib inhibits PDGFR and c-kit. As monotherapy, it showed no clinical activity. Combination trials with chemotherapy are ongoing.
Metastatic breast cancer; Tyrosine kinase inhibitor; Her-2/neu; Anti-angiogenesis; Intracellular kinase pathways
As long-term survivors of breast cancer after autologous peripheral blood stem cell transplantation (ASCT) are becoming more numerous, studies addressing the issue of long-term follow-up are necessary. In this study, we report on the quality of life (QOL) after ASCT and high-dose chemotherapy (HDCT).
Patients and Methods
The QOL questionnaire version 3.0 by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30 version 3.0) was filled in by patients and healthy controls at 5 time points. After obtaining the results, we analyzed the correlation between QOL and the effect factors.
Some functions got significantly worse, and some symptoms got more serious after ASCT and HDCT. However, most of them improved with time and were comparable to the healthy controls after 5 years. QOL was in part related to age, tumor characteristics, educational level, marriage status, and income.
Evaluating QOL allows medical workers to fully understand a patient's state of health, and aid the estimation and selection of clinical treatment methods as well as improve recovery.
Quality of life; Autologous peripheral blood stem cell transplantation; High-risk breast cancer
Medical studies have shown that switching to exemestane after 2-3 years of adjuvant treatment with tamoxifen is effective when looking at overall survival. No cost effectiveness study of exemestane has been conducted in the German health care context.
Patients and Methods
To assess the cost effectiveness of switching to exemestane vs. continued tamoxifen therapy for early-stage breast cancer, a Markov model was developed. The model population was set as postmenopausal women who are in remission from early-stage breast cancer. Upon model entry, either a continuing daily therapy with 20 mg tamoxifen or a switch to 25 mg exemestane for the next 2-3 years takes place. The model takes a German health care perspective.
The total incremental costs of exemestane on a lifetime basis are 4,195 Euro, resulting in an incremental cost effectiveness ratio of 17,632 Euro per additional quality-adjusted life year (QALY), or 16,857 Euro per life year gained. Incremental costs per disease-free year of survival are 12,851 Euro. Probabilistic sensitivity analyses proved the robustness of these findings.
Compared to extended tamoxifen therapy, switching to exemestane after 2-3 years turned out to be a cost-effective strategy in adjuvant therapy for early-stage breast cancer in postmenopausal women within the German health care context.
Aromatase inhibitors; Postmenopause; Cost effectiveness; Breast cancer; Early stage
Inflammatory breast cancer is a rare, yet controversial, syndrome of invasive breast cancer.
A female, Caucasian, 57-year-old patient presented at the emergency department with complaints suggestive of inflammatory breast cancer.
Inflammatory breast cancer, besides the advances on its molecular profile, still remains a clinical entity difficult to diagnose, especially in the primary health care setting.
Breast cancer; locally advanced, metastatic; Bone metastasis; Differential diagnosis; Inflammation
Nodular fasciitis of the breast is a rare benign pathology that can mimic breast cancer clinically, radiologically, and histopathologically.
An 18-year-old female patient had first visited a physician in a different center with the complaint of a lump in her left breast. Breast examination had revealed a palpable mass located in the left upper outer quadrant. Ultrasonography had demonstrated a hypoechoic lesion. Excisional biopsy of the lump had been performed and histopathologic examination misdiagnosed this lump as a mesenchymal tumor. The patient was then referred to our clinic for further investigations. Pathologic revision was performed and the diagnosis of nodular fasciitis of the breast was established.
Awareness of this rare clinical entity, nodular fasciitis, in the breast eliminates the misdiagnosis of breast cancer.
Nodular fasciitis; Breast; Pathology
Primary angiosarcoma of the breast (PAB) is a rare occurrence of highly aggressive biological behavior. Bilateral PAB is even more infrequent.
We present the case of a 39-year-old Chinese woman with metachronous bilateral PAB (2005 and 2008). The diagnosis of PAB was confirmed. The respective masses were removed via simple mastectomy. The extent of malignancy differed microscopically between the two tumors and indicated a different source. After two surgeries and a 3-year follow-up, the patient is alive and well. The current case illustrates an unusual presentation of this rare type of breast sarcoma, in that none of the clin-icopathological findings are thought to confer a good prognosis. We also review the literature and summarize relevant findings concerning definition, pathology, clinical features, treatment, and follow-up.
We believe that the survival rate depends on tumor size and differentiation. Surgical resection followed by chemotherapy may prove to be effective and afford the best prognosis in the future.
Breast angiosarcoma; Primary angiosarcoma; Bilateral; Breast sarcoma
We aimed to take a snapshot of breast units in the European Union 9 years after the publication of the European Society of Mastology (EUSOMA) position paper.
In order to obtain information on breast units throughout the European Union, we designed a questionnaire comprising 5 questions on certification, audit frequency and number of breast units in each country. Our primary contacts were national cancer societies, breast cancer study groups, breast cancer organizations, national associations and societies of breast treatment, as well as experts in the field of breast cancer.
Information on characteristics of the certification process and number of breast units was obtained for 9 countries of the European Union. 7 of the 9 countries (78%) have a certification process of the breast units. Certification is carried out by public authorities in 4 (57%) countries and by private companies in 3 (43%) countries. Information on frequency of auditing was reported in 4 countries and varied between annual audits (Austria, Ireland and Germany) and audits once every 3 years (United Kingdom).
The current study suggests that the European breast unit landscape is a heterogeneous field. 9 years after the EUSOMA position paper, we do not have any standard European guidelines, neither for the development nor for the mandatory prerequisites of a breast unit. The development and operation of breast units are still country specific.
Breast units; Breast cancer; Certification criteria
A decrease in medical practice variations in national breast cancer care has been shown to improve survival and the negative impact of the disease on affected women and their families. The following report describes the concert of efforts undertaken by the medical societies to optimize national breast cancer care by organizational centralization of multidisciplinary medical competence in certified breast centers (CBC), aiming to attain continual quality of health care by implementation of evidence-and consensus-based guidelines. Centralization and the systematic pursuit of organizational development by tracking guideline adherence using performance quality indicators over time demonstrate the feasibility and practicability of the implementation concept to bridge the gap between determined scientific best evidence and applied best practice. However, the proof of concept will remain pending until the data of the population-based cancer registries are analyzed for survival estimates.
Breast neoplasms; Breast center; Certification; Guidelines; Quality of care
With its high incidence and long history of patient advocacy, breast cancer has generated the most concern about the quality of its care and the volume-outcome relationship. In breast cancer surgery, the risk of perioperative morbidity or mortality is low, but surgery is only one single piece in the mosaic of multidisciplinary care that eventually determines survival. Only a limited number of articles is available investigating the relationship between case volume of physicians and hospitals and specialization of surgeons and survival. In summary, there is evidence to support the hypothesis that specialization, research interest, and caseload of physicians and hospitals is positively correlated with providing state-of-the-art care and with survival. However, it is less clear what impact might be attributed to the surgical routine gained with increasing number of procedures compared to the deeper insight into the biology of breast cancer that comes with specialization in oncology and the weight of the multidisciplinary setting that is more easily established and maintained with a higher caseload.
Breast cancer; Caseload; Survival; Specialization
The German health care system has entered an era of specialist centers and certification. Hospitals are required to introduce quality management with external monitoring, refining and improving their quality of treatment. These statutory requirements can only be met through specialization, centralization, and establishing centers and networks with internal and external interdisciplinary collaboration. The breast centers certified according to the criteria of the German Cancer Society (DKG) and German Society for Mastology (DGS) are pioneers here. Simultaneously, there are increasing demands for more cost-effective medical services despite limited resources – making economic analysis of health care provision necessary. Few economic studies of the centers and certification system have been conducted, however. General long-term quality data, particularly for results, are not yet available from certified breast centers. At present, a certified breast center is not itself a proven independent prognostic parameter for treatment results. However, the individual criteria required for breast center certification show a significant positive influence on clinical efficacy. Certified breast centers involve substantial extra costs that are not reimbursed by funding bodies, so the slightest potential benefit for patients from certified centers already appears cost-effective. When the actual costs, currently usually subsidized by other departments, are considered, it is unclear whether certified breast centers remain cost-effective.
Breast center; Breast cancer; Certification; Accreditation; Cost-effectiveness analysis
Granulomatous disease within the breast can result from a variety of causes.
Patients and Methods
We present 3 cases of this condition with 3 different underlying diagnoses.
Each case was initially labelled as idiopathic granulomatous mastitis, although this was proven not to be correct on further investigation.
Clearly, identifying the correct underlying diagnosis is essential in granulomatous breast lesions as the treatment varies widely depending on the underlying aetiology. Effective communication and feedback in the context of the multidisciplinary team are vital to the diagnostic process in such challenging cases.
Granulomatous mastitis; Breast
The purpose of this study was to define the diagnostic accuracy of mammography and ultrasound in the evaluation of male breast disease, and to suggest a diagnostic protocol for male breast disease.
Material and Methods
We retrospectively reviewed clinical, radiographic, and pathologic records of 75 patients. Breast Imaging Reporting and Data System (BI-RADS) category 4-5 mammograms and ultrasonograms were suggested as suspicious for malignancy.
Of the 75 patients, 23 (31%) were considered to have suspicious lesions by mammography and/or ultrasonography. 13 of the patients were shown to have breast cancer. The remaining 52 (69%) were referred for biopsy by clinicians; all of the biopsy specimens were benign (gynecomastia). The accuracy data of mammography and ultrasonography are: sensitivity, 69 and 100%; specificity, 87 and 97%; positive predictive value, 53 and 87%; negative predictive value, 93 and 100%; and accuracy, 84 and 97%, respectively.
We suggest a new diagnostic algorithm for the evaluation of male breast disease in which ultrasonography may be used to evaluate palpable abnormalities as the first diagnostic tool of choice. To use and to trust imaging would decrease the number of false-positive biopsies that would be generated by physical examination alone.
Male breast cancer; Ultrasound; Mammography
Malignant peripheral nerve sheath tumors are rare tumor entities that originate from peripheral nerve sheaths and have an unfavorable prognosis. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an absolutely rare location of this lesion, and presentation as a breast lump in the male breast is even rarer.
A 65-year-old man presented with a 6-month history of a painless mass of the left breast. Tissue biopsy was performed. Histopathology revealed a malignant spindle cell tumor which was confirmed to be a melanocytic malignant peripheral nerve sheath tumor on the basis of immunopositivity for HMB45 and S-100.
There are no generally accepted guidelines for the treatment of malignant peripheral nerve sheath tumors in the male breast. The patient was referred for radiation therapy after simple mastectomy.
Malignant peripheral nerve sheath tumor; Breast; Melanocytic
Breast centers (BRCs) in Austria are currently managed and will be managed in the future as interdisciplinary and largely virtual, well-structured entities. The goals of the initiative to set up these centers are convergence of care, enhancement of the quality of care delivered to women diagnosed with breast cancer, and a significant actual benefit for the affected women. Given the geographical and infrastructural circumstances and partly already existing diagnostic and therapeutic facilities, a collaborating center model seems to be the target-oriented solution to employ the already existing resources. Evaluation and optimization of outcome quality (i.e. overall survival rate, disease-free survival, breast conservation rate, etc.) necessitate the implementation of treatment pathways with data collection and recording in a central registry. The aim should be to create an independent ‘neutral’ certification commission (a standard setter) in order to adapt the requirements of BRCs to Austrian circumstances. An appointed certification agency reviews compliance with the specifications of the certification commission. The European Society of Mastology (EUSOMA) specifications, as laid down in the European Parliament, serve as guidelines. These specifications were compiled by the brain trust of the Austrian Federal Institute of Health (ÖBIG) in Chapter 3.6.11 ‘Breast Health Centers’ for implementation in the Austrian Health Care Structure Plan (ÖSG). BRCs in Austria should demonstrate a minimum caseload of 100 primary diagnoses per year. The collaborating partners – the affiliated centers – may, however, join a BRC with a demonstrated minimum caseload of 30 per year. In this model, the outcome quality should be achieved even with a smaller caseload with structure quality assurance. It is planned that, by the end of 2016, breast health centers will take over the comprehensive care of breast cancer patients nationwide. Center certification is viewed as quality enhancement since care is provided to all patients on a verifiable high quality level, subject to constant improvements.
Breast Health Center; Collaborating Center; Certification; Certification Commission; Austrian Health Care Structure Plan; Quality
With 28% of all cancers, breast cancer is the most common cancer in the Austrian female population (also worldwide), and incidence has shown a development similar to that in most of the Western European countries. Several studies reveal a higher incidence of breast cancer in women of higher socioeconomic status (SES) compared to women of lower SES. Later age of first childbearing, low total parity, significantly greater use of hormone replacement therapy, and a greater use of mammography screening by women of higher SES are possible explanations for these trends. Socioeconomic inequalities have a strong influence on the subjective perception of health, but also on objective indicators of the health situation. The health behavior of the Austrian population is, of course, determined by social factors. People with a higher socioeconomic status not only live longer than people with a lower SES, they also have a healthier lifestyle and they better assess their own health status. These inequalities can also be observed in significant differences in life expectancy between university graduates and low-educated people (6.2 years for men and 2.6 years for women).
Breast cancer; Socioeconomic status; Austria
Quality of life (QOL) has become a widely used outcome parameter in the evaluation of treatment modalities in clinical oncology research. By now, many of the practical problems associated with measuring QOL in clinical practice can be overcome by the use of computer-based assessment methods. QOL assessment in oncology is dominated by two measurement systems, the FACT scales and the EORTC QLQ-C30 with its modules. The amount of human resources required to implement routine data collection has been reduced significantly by advanced computer technology allowing data collection in busy clinical practice. Monitoring of QOL can contribute to oncologic care by facilitating detection of physical and psychological problems and tracking the course of disease and treatment over time. Furthermore, the integration of screening for psychosocial problems into QOL monitoring contributes to the identification of patients who are in need of psychooncologic interventions. Computer-based QOL monitoring does not replace the direct physician-patient communication but enables to identify specific impairments and symptoms including psychological problems. Beyond clinical practice, QOL data can be used for research purposes and may help health care planners to determine those patient services that should be maintained or ones that should be developed.
Breast neoplasms; Quality of life; Computers; Monitoring; Review
Breast cancer remains the most prevalent cancer diagnosed in women worldwide. The number of effective treatments for breast cancer is on the rise, however, the benefit from specific treatments to individual patients and the adverse events experienced vary considerably. Efficacy and safety of anticancer therapies may depend on tumor, treatment, and host characteristics. Advances in the adjuvant chemotherapy of operable breast cancer have come from the introduction of effective agents and the application of the principles of combination chemotherapy. Attempts to advance these principles by substantial escalation of drug dosage have proven unsuccessful with a potentially higher rate of side effects. Another concept to increase efficacy is dose density, the administration of drugs with shortened intertreatment interval, and sequential therapy. The dose-dense concept improved clinical outcome significantly and was not accompanied by an increase in toxicity.
Breast cancer; Chemotherapy: dose-dense, tailored; Efficacy; Toxicity; Dose intensification
Recent advances in adjuvant treatment of breast cancer have improved progression-free and overall survival. Optimal management of treatment-induced side effects has therefore gained further importance. This review cannot provide a comprehensive overview of treatment-related toxicity and its management, but focuses on important new developments in the field of supportive therapy. Erythropoietins, while highly effective in treating chemotherapy-induced anaemia, may have detrimental effects on outcome, and should only be used with the aim to reduce the number of whole blood transfusions. Granulocyte colony-stimulating factors were a prerequisite for development of dose-dense regimens, and are also necessary in many anthracycline/taxane combination regimens. A potential tumour-stimulating effect was not proven in solid cancers. For side effects of conventional chemotherapy, such as mucositis, nausea, or diarrhoea, regularly updated guidelines may improve symptom control. Overall, modern supportive treatment tools will further reduce treatment-related mortality and help increase quality of life.
Adjuvant treatment; Breast cancer; Growth factors; Side effects; Supportive care