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1.  Primary Actinomycosis of the Breast Masquerading as Malignancy: Diagnosis by Fine Needle Aspiration Cytology 
Breast Care  2012;7(2):153-154.
PMCID: PMC3376359  PMID: 22740805
Actinomycosis; Malignancy; Breast; Cytology
2.  ABC2 Consensus Conference on Advanced Breast Cancer: Brief Summary of the Consensus Panel on Saturday November 9, 2013 
Breast Care  2013;8(6):455-456.
PMCID: PMC3919429  PMID: 24550756
ABC2 Consensus; Metastatic breast cancer
3.  Bridging the Gap – an Update of Translational Research in Breast Cancer 
Breast Care  2013;8(6):397-398.
PMCID: PMC3919422  PMID: 24550746
4.  Idiopathic Granulomatous Lobular Mastitis – Report of 43 Cases from Iran; Introducing a Preliminary Clinical Practice Guideline 
Breast Care  2013;8(6):439-443.
We aimed to report a large series of idiopathic granulomatous lobular mastitis (IGLM) from Iran and sketch preliminary clinical practice guidelines (CPG) for approaching an inflammatory breast mass.
Patients and Methods
In a retrospective records review, 43 consecutive IGLM cases were studied. Data on baseline, clinical, imaging, and pathologic characteristics were collected.
The mean age of the women was 33.5 years. All but 1 were married and had given birth. 16% had a cancer-like presentation. Inflammatory signs, architectural distortion, and a nodular pattern were the most common findings clinically, mammographically and ultrasonographically, respectively. 29.5% of the pathological reports indicated necrosis which was more common in younger subjects (p = 0.016); microabscesses were associated with a shorter lactation course (p = 0.006). Corticosteroids had been used as the initial treatment modality in 51%, immunosuppressive agents had not been administered, and a 16% relapse rate was recorded. We recognized the need for a multidisciplinary approach covering radiology, oncology, and surgery to best handle diagnostic and therapeutic issues and manage relevant infections as well as the major differential diagnosis, i.e. malignancy.
We hypothesized that a shorter lactation period may cause more milk stasis and extravasation and be contributory to IGLM. CPGs are needed to incorporate the needed multidisciplinary approach and to standardize IGLM care. We present one such guideline.
PMCID: PMC3919426  PMID: 24550752
Idiopathic granulomatous lobular mastitis; Multidisciplinary approach; Treatment strategies; Clinical practice guidelines; Iran; Milk extravasation; Breast-feeding; Relapse
5.  Genomic Profiling in Luminal Breast Cancer 
Breast Care  2013;8(6):414-422.
The developments in gene expression analysis have made it possible to sub-classify hormone receptor-positive (luminal) breast cancer in different prognostic subgroups. This sub-classification is currently used in clinical routine as prognostic signature (e.g. 21-gene Onoctype DX®, 70-gene Mammaprint®). As yet, the optimal method for sub-classification has not been defined. Moreover, there is no evidence from prospective trials. This review explores widely used genomic signatures in luminal breast cancer, making a critical appraisal of evidence from retrospective/prospective trials. It is based on systematic literature search performed using Medline (accessed September 2013) and abstracts presented at the Annual Meeting of American Society of Clinical Oncology and San Antonio Breast Cancer Symposium.
PMCID: PMC3919430  PMID: 24550749
Biomarker; Breast cancer; Gene expression; Prognostic markers; Luminal breast cancer
6.  Genomic Profiling in Triple-Negative Breast Cancer 
Breast Care  2013;8(6):408-413.
Triple-negative breast cancer (TNBC) is defined by a lack of hormone receptor expression as well as lack of overexpression/amplification of HER2/neu. Patients with TNBC show a significantly worse prognosis compared to patients with other breast cancer subtypes. TNBC, however, is a heterogeneous entity both with regard to clinical/pathological characteristics and molecular biology. This review summarizes the current data on TNBC with a particular focus on mutational and gene expression profiling and the association between TNBC and breast cancer stem cells.
PMCID: PMC3919434  PMID: 24550748
Triple negative breast cancer, subtypes; Whole genome sequencing; RNA profiling; Heterogeneity
7.  High-Throughput Gene Expression and Mutation Profiling: Current Methods and Future Perspectives 
Breast Care  2013;8(6):401-406.
Following the completion of the human genome sequence at the beginning of the new millennium, a series of high-throughput methods have changed cancer research. Using these techniques, global analysis such as expression profiling could be carried out on a genomic scale. In breast cancer they led to the classification of the intrinsic subtypes, and the development of several prognostic and predictive ‘genomic tests’ for patient stratification. During the last 2 years we have faced a similar dramatic revolution with the introduction of next generation sequencing (NGS). These techniques allow sequencing of the complete human exome or whole genome with a cost reduction in the order of 10,000–100,000 fold. Consequently, the number of known cancer genome sequences exploded with more than 6,000 samples, published between 2011 and 2013. These studies have led to important and surprising discoveries both for basic cancer research and clinical applications. They relate to understanding the development of cancer as well as the heterogeneity of the disease, and how to use this information to guide the development and application of therapies. Although it is foreseeable that the sequencing surveys of neoplasms will soon conclude, their introduction into clinical practice is just beginning.
PMCID: PMC3919435  PMID: 24550747
Gene expression profiling; Next-generation sequencing; Breast cancer, molecular subtypes; Cancer genome; Tumor heterogeneity
9.  Radiation Oncologists’ View on the Zurich Consensus 
Breast Care  2013;8(6):448-452.
PMCID: PMC3919487  PMID: 24550754
St. Gallen Consensus; Radiation Oncology; Breast Cancer
10.  Safety of Tamoxifen During Pregnancy: 3 Case Reports and Review of the Literature 
Breast Care  2013;8(6):453-454.
PMCID: PMC3919494  PMID: 24550755
Breast cancer; Pregnancy; Tamoxifen
11.  Axillary Arch May Affect Axillary Lymphadenectomy 
Breast Care  2013;8(6):424-427.
The aim of this study was to identify the axillopectoral muscle anomaly commonly known as Langer's axillary arch, and to understand its importance in surgical procedures of the axilla.
Patients and Methods
Between 2009 and 2011, 758 patients underwent sentinel lymph node biopsy, axillary dissection, or both. Patients with Langer's axillary arch were identified and assessed retrospectively. The decision to cut or preserve the axillary arch was made based on clinical judgment, and patients were followed-up accordingly to monitor for adverse outcomes.
Of the 758 patients who underwent axillary procedures, 9 (1.2%) were found to have a Langer's axillary arch. In 2 patients the arch was cut, and in 7 patients it was preserved. No adverse outcomes were identified in any of the patients upon follow-up.
Langer's axillary arch is a unique anatomic anomaly of the axillary region that may be problematic due to the potential risks of lymphedema and vascular or nerve compression. It is important for surgeons and radiologists alike to be aware of this anatomic variation in order to properly identify it and respond appropriately based on clinical judgment, and to complete close follow-up of the patient due to the potentially increased risk of adverse outcomes.
PMCID: PMC3919495  PMID: 24550750
Langer's axillary arch; Axillary lymphadenectomy; Anatomic anomaly of the axilla
12.  Primary Mucinous Cystadenocarcinoma of the Breast with Endocervical-Like Mucinous Epithelium 
Breast Care  2013;8(6):445-447.
Primary mucinous cystadenocarcinoma of the breast is an extremely rare entity. To the best of our knowledge, only 17 patients have been described in the PubMed database.
Case Report
Here, we report a primary breast mucinous cystadenocarcinoma with endocervical-like mucinous epithelium in a 62-year-old woman. The patient was followed for 5 months without any adjuvant treatment and she continues to be disease free.
Primary breast mucinous cystadenocarcinoma usually displays unique pathologic and immunohistochemical characteristics simulating its ovarian counterparts; it seems to have a good prognosis after complete resection.
PMCID: PMC3919496  PMID: 24550753
Breast cancer; Mucinous cystadenocarcinoma; Immunohistochemistry
13.  Cost-Effectiveness of Lapatinib plus Letrozole in Post-Menopausal Women with Hormone Receptor-and HER2-Positive Metastatic Breast Cancer 
Breast Care  2013;8(6):429-437.
In the EGF30008 and TAnDEM (TrAstuzumab in Dual HER2 ER-positive Metastatic breast cancer) trials, anti-HER2 therapy plus an aromatase inhibitor (lapatinib + letrozole (LAP + LET) and trastuzumb + anastrozole (TZ + ANA), respectively) improved time to progression versus aromatase inhibitor monotherapy (LET and ANA, respectively) in post-menopausal women with previously untreated hormone receptor-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer.
A partitionedsurvival analysis model using data from EGF30008 and published results of TAnDEM and other literature was used to evaluate the incremental direct medical cost per quality-adjusted life year (QALY) gained with LAP + LET versus LET, ANA, and TZ + ANA in post-menopausal women with previously untreated HR+ and HER2+ metastatic breast cancer from the UK National Health Service (NHS) perspective.
Incremental costs for LAP + LET are £ 34,737 versus LET, £ 35,995 versus ANA, and £ 5,513 versus TZ + ANA. Corresponding QALYs gained are 0.467, 0.601, and 0.252 years. Cost/QALY gained with LAP + LET is £ 74,448 versus LET, £ 59,895 versus ANA, and £ 21,836 versus TZ + ANA. Given a threshold of £ 30,000/QALY, the estimated probability that LAP + LET is cost-effective is 1.4% versus LET, 9.2% versus ANA, and 51% versus TZ + ANA.
Based on criteria for the evaluation of health technologies in the UK (£ 30,000/QALY), LAP + LET is not likely to be cost-effective versus aromatase inhibitor monotherapy but may be cost-effective versus TZ + ANA, although the latter comparison is associated with substantial uncertainty.
PMCID: PMC3919502  PMID: 24550751
Aromatase inhibitors; Breast cancer; Combination therapy; Costs; HER2; Hormonal treatment; Metastatic disease; Trastuzumab; Lapatinib
14.  Is Symptom-Oriented Follow-Up Still Up to Date? 
Breast Care  2013;8(5):336-340.
The main objective of following patients after the primary treatment of breast cancer is the detection of potentially curable events, particularly the detection of local recurrences and contralateral breast cancer. Additionally, medical counseling on therapies, psychosocial aspects, side effects of therapies, and lifestyle interventions is important to improve the quality of life. There is an ongoing discussion about whether early detection of asymptomatic metastasis could improve the course of disease. Today, the follow-up is still symptom-orientated. Intensified imaging and laboratory check-ups have not been beneficial for the patients’ survival. A follow-up in the first 2–3 years is recommended every 3 months. Because of the decreasing incidence of recurrence from year 4, 6-monthly screening intervals are recommended. The screening should include a history, physical examination, and a consultation. Routine diagnostic imaging – except for mammography/ultrasound – is not indicated in asymptomatic patients. Innovative therapies for patients with metastatic breast cancer have been introduced. Therefore, measures of an intensified follow-up could change in the future as novel endocrine combination or targeted therapies in molecular subtypes could significantly improve the survival in early detected metastasis. In the future, more individualized follow-up programs are conceivable. However, this idea is so far not supported by the available data.
PMCID: PMC3861877  PMID: 24415986
Breast cancer follow-up; Imaging; Laboratory check-up; Lead time; Breast cancer subtypes
15.  Commonly Used Methods of Complementary Medicine in the Treatment of Breast Cancer 
Breast Care  2013;8(5):341-347.
Many patients with cancer look for information on complementary or alternative medicine (CAM) and use various CAM methods. Women with breast cancer are amongst the most avid users. Patients in Europe prefer drug-bound CAM methods, which are prone to side effects and drug interactions. In order to reduce these risks, communication between the patient and the physician on CAM is indispensible. Yet, most patients do not discuss CAM in general and complementary drug therapy in particular with their oncologists and most oncologists themselves are not overly familiar with the topic. This article gives an overview on the most often used CAM methods with regard to breast cancer. The current state of the scientific evidence, the benefits and risks are summarized.
PMCID: PMC3861850  PMID: 24415987
Complementary medicine; Alternative medicine; Supplements; Supportive therapy; Breast cancer; Evidence based medicine
16.  Subclinical Breast Cancer: Minimally Invasive Approaches. Our Experience with Percutaneous Radiofrequency Ablation vs. Cryotherapy 
Breast Care  2013;8(5):356-360.
The aim of this study was to compare the efficacy of radiofrequency ablation vs. cryoablation in the treatment of early breast cancer.
Patients and Methods
80 women (mean age 73 ± 5 years) with early breast cancer were retrospectively evaluated. 40 patients underwent cryoablation and 40 patients underwent radiofrequency ablation, both with sentinel lymph node excision. Tumor volume and histopatological data were compared by means of postprocedural 3.0-T magnetic resonance imaging (MRI). 30–45 days after the percutaneous ablation, all patients underwent surgical resection of the tumor. The mean follow-up was 18 months without any local recurrences.
Both techniques allow good correlation with histopathological data. In 75 patients (93.8%) we observed complete necrosis; in 5 cases there was residual disease in the postprocedural MRI and postoperative histological examination. There was a good correlation between MRI volume and histologic samples. Cosmetic results were good in all patients but 2.
Both percutaneous radiofrequency ablation and cryotherapy are minimally invasive techniques with a good clinical and cosmetic outcome in selected cases. MRI examination is an ideal method to assess breast neoplasms in terms of quality and quantity as well as residual tumor extent after percutaneous ablation. Cryotherapy is the preferred method because of the analgesic effect of freezing with better patients compliance.
PMCID: PMC3861851  PMID: 24415989
Cryoablation; Radiofrequency ablation; Breast cancer; Percutaneous ablation; MRI; Minimally invasive techniques
17.  Axillary Irradiation with High Tangent Fields for Clinically Node-Negative Breast Cancer: Can 3-D Conformal Radiotherapy with a Field-in-Field Technique Better Control the Axilla? 
Breast Care  2013;8(5):362-367.
The target volume for postoperative breast irradiation is the remaining breast tissue, and the axillary region is not an intentional target volume.
Patients and Methods
Between 2001 and 2009, eligible women with pT1–2cN0/pN0(sn) breast cancer underwent breast-conserving therapy without axillary dissection. Treatment outcomes between 2 radiotherapy planning groups, high tangent fields with 2-dimensional (2-D) simulation-based planning and 3-dimensional (3-D) computed tomography-based planning with a field-in-field technique, were compared. The correlating factors for axillary failure were also calculated.
In total, 678 patients were eligible. As of May 2009, the median follow-up times for the 2-D (n = 346) and 3-D (n = 332) groups were 94 and 52 months, respectively. Patient characteristics were balanced, except for a younger population in the 2-D group and more lymphovascular invasion in the 3-D group. On multivariate analysis, 2-D planning was the only risk factor for axillary failure. In the 2-D and 3-D groups, the 5-year cumulative incidences of axillary failure were 8 (3.1%) and 1 (0.3%) (log-rank p = 0.009), respectively. The respective 5-year overall survival rates were 97.4 and 98.4% (p = 0.4).
High tangent irradiation with 3-D planning improved axillary control compared to that with 2-D planning, suggesting that optimizing axillary dose distribution may impact outcomes.
PMCID: PMC3861852  PMID: 24415990
Breast cancer; Conformal radiotherapy; Sentinel lymph node biopsy
18.  Malpractice Leading to Secondary Lymphedema after Radical Mastectomy: Case Report 
Breast Care  2013;8(5):371-373.
With this case report we want to demonstrate the results of chemotherapy application to the mastectomized side in a patient who had undergone radical mastectomy.
Case Report
A patient who was accidentally given chemotherapy on the mastectomized side (PCMS) and a control patient who received chemotherapy on the non-affected side (PCNS) were included in this study. Edema, pain, muscle strength, and shoulder mobility were evaluated. The results of the 2 patients were compared. After chemotherapy, PCMS experienced edema and pain in the affected arm compared to PCNS. Increased circumference measurement, and decreased shoulder mobility and muscle strength were observed in PCMS.
It was suggested that chemotherapy application on the mastectomized side triggered lymphedema. Our findings on the subject revealed that education of health care professionals and patients alike is very important.
PMCID: PMC3861855  PMID: 24415992
Breast cancer; Chemotherapy; Pain; Edema
19.  Physical Activity in Breast Cancer Patients during Medical Treatment and in the Aftercare – a Review 
Breast Care  2013;8(5):330-334.
Most scientific studies regarding physical activity in cancer patients involve breast cancer patients. It is apparent that physical activity during medical treatment and aftercare is not only feasible and safe but also effective. Current studies clearly show that regular and specific endurance and/or resistance training can reduce a number of side effects caused by medical treatment. Among others, improvements in physical performance, body composition, and quality of life as well as a reduction in fatigue, have been observed. Since inactivity appears to exacerbate lymphedema, patients with lymphedema are also encouraged to exercise. Few studies have been carried out regarding physical exercise in metastatic patients. However, experts in the field also recommend regular physical activity for patients with advanced-stage breast cancer.
PMCID: PMC3861858  PMID: 24415985
Physical activity; Exercise; Breast cancer
20.  Patient-Centered Additional Offers in Breast Centers 
Breast Care  2013;8(5):329.
PMCID: PMC3861873  PMID: 24415984
21.  The Oncological Emergency Case: Paraneoplastic Hypoglycemia in Metastatic Breast Cancer – Case Report and Brief Review of the Literature 
Breast Care  2013;8(5):368-370.
Paraneoplastic hypoglycemia is a rare syndrome amoung tumorous diseases. It is often associated with a paraneoplastic secretion of ‘big’ insulin-like growth factor-II.
We describe this syndrome in a 60-year-old patient with advanced breast cancer 8 years after primary diagnosis.
Results and Conclusion
This non-islet cell tumor-induced hypoglycemia may be the only evidence for an otherwise clinically occult disease progression. Fast diagnosis and appropriate acute and causal treatment concepts should be part of oncological management.
PMCID: PMC3861876  PMID: 24415991
Hypoglycemia; Breast cancer; Metastases; Insulin-like growth factor; Paraneoplastic
22.  Comparison of Ductoscopy, Galactography, and Imaging Modalities for the Evaluation of Intraductal Lesions: A Critical Review 
Breast Care  2013;8(5):348-354.
Today, in cases of nipple discharge of unclear origin, the abundance of diagnostic procedures – a, diagnostic dilemma’ – becomes apparent, because unequivocal indications and a current, standardized examination sequence are presently not available. The diagnostic workup of patients with nipple discharge usually includes the clinical history, physical examination, mammography, ultrasonography, galactography, and nipple discharge cytology, but not ductoscopy.
In this review we analyze and discuss the possible role of ductoscopy in evaluating intraductal pathologies and its combined use with diagnostic imaging modalities. For this purpose, we reviewed and compared the results of the radiological, pathological, and surgical studies independently.
Currently, there is no solitary accurate modality to reach our definitive purpose. Being aware of the capability of each diagnostic modality may take us closer to our target. Therefore, adjunct and appropriate use of multiple imaging modalities and ductoscopy is necessary to evaluate patients with nipple discharge.
PMCID: PMC3862052  PMID: 24415988
Ductoscopy; Imaging methods; Biopsy; Papilloma; Ductal carcinoma
23.  Bidirectional Crosstalk between the Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Signaling Pathways in Breast Cancer: Molecular Basis and Clinical Implications 
Breast Care  2013;8(4):256-262.
The estrogen receptor (ER) and/or the human epidermal growth factor receptor 2 (HER2) signaling pathways are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. As a result, targeting these pathways provides the most effective therapies in appropriately selected patients. Nevertheless, resistance to both endocrine and anti-HER2 therapies occurs frequently and represents a major clinical challenge. Compelling preclinical and clinical evidence relates this treatment resistance to the presence of a complex bidirectional molecular crosstalk between the ER and HER2 pathways. As a consequence, treatment strategies targeting either pathway are associated with up-regulation of the other one, ultimately resulting in resistance to therapy. Therefore, a more promising strategy to prevent or overcome either endocrine or anti-HER2 resistance at least in some tumors is to combine targeted treatments that simultaneously block both signaling pathways. Many clinical trials exploring this strategy have shown positive results, and many more are currently ongoing. Future clinical trials with appropriate patient selection, based on biomarker evaluation of primary tumors and possibly of recurrent lesions, are warranted for the optimization of individualized therapeutic strategies.
PMCID: PMC3808214  PMID: 24415978
Estrogen Receptor; HER2; Crosstalk; Resistance
24.  Cross-National Comparison of Medical Costs Shared by Payers and Patients: A Study of Postmenopausal Women with Early-Stage Breast Cancer Based on Assumption Case Scenarios and Reimbursement Fees 
Breast Care  2013;8(4):282-288.
The objectives of this study were to estimate and cross-nationally compare the medical costs shared by payers and patients and the distributions of medical costs by cost category.
Material and Methods
We estimated the medical costs covered from definitive diagnosis to completion of treatments of early-stage breast cancer and follow-up, assuming almost identical medical care provided in Japan, the UK, and Germany. The analysis was performed from the payer's perspective. Medical costs were calculated by multiplying the unit costs by the number of units consumed, based on assumption case scenarios. The medical costs incurred by payers or patients were estimated according to the cost-sharing and the cost-bearing systems in each country.
The total medical costs in Japan were much lower than those in the UK and Germany, and these differences were mainly caused by the low costs of surgery and radiotherapy in Japan. For the base-case scenario, the co-payment in Japan (€ 3,486) was found to be 6.4-fold higher than that in Germany (€ 548). The payers in the European countries paid 2.9-fold more than those in Japan (€ ∼25,000 vs. € 8,627).
Our results will be useful for policy makers in considering how to share medical costs and how to allocate limited resources.
PMCID: PMC3808215  PMID: 24415981
Health care system; Reimbursement; Cost-sharing; Breast cancer
25.  Endocrine Resistance in Breast Cancer: Focus on the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway 
Breast Care  2013;8(4):248-255.
Breast cancer is the most common cancer among women. Up to 75% of breast cancers express the estrogen receptor (ER)α and/or the progesterone receptor (PR). Patients with hormone receptor-positive metastatic breast cancer are typically treated with endocrine therapy. Yet, not all patients with metastatic breast cancer respond to endocrine treatments and are considered to have primary (de novo) resistance. Furthermore, all patients who initially respond to endocrine treatment will eventually develop acquired resistance. Several mechanisms have been linked to the development of endocrine resistance, including reduced expression of ERα, altered regulation of the ER pathway, and activation of various growth factor signaling pathways, among them the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. This pathway is involved in critical processes including cell survival, proliferation, and angiogenesis, and plays a central role in breast cancer development. Recent laboratory and clinical data implicate this pathway as mediating endocrine resistance, and agents directed against critical components of this pathway are either already approved for clinical use in breast cancer patients or are currently being tested in clinical trials. In this review, we describe the interaction between the PI3K/Akt/mTOR pathway and the ER cascade, its role in mediating endocrine resistance, and the clinical implications of this interaction.
PMCID: PMC3808218  PMID: 24415977
Hormone receptor-positive breast cancer; Estrogen receptor; Endocrine resistance; PI3K/mTOR pathway

Results 1-25 (401)