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.

Background

The aim of this article was to evaluate the prognostic value of the MammaPrintTM signature in women $$ 60 years with invasive breast cancer.

Patients and Methods

60 female patients were included in this prospective study. Eligibility criteria included: pT1c-3, pN0–1a, grade 2/3, hormone receptor-positive and HER2-negative tumor. The clinical risk was determined by Adjuvant! Online (AOL).

Results

38 patients (63%) where considered to be low-risk patients by the 70-gene signature, while 22 (37%) were considered to be high-risk patients. No statistically significant differences between low- and high-risk groups could be detected for conventional prognostic parameters, particularly not for Ki-67. By AOL, 33 patients (55%) were considered to be at high risk, of which 20 had a discordant MammaPrintTM result. The discordance rate between the profile and AOL was 48%, which is higher than in previous publications. When the 70-gene signature was used in combination with the clinical risk assessment, the recommendation for adjuvant systemic treatment differed in 11 patients (18%).

Conclusions

In the intermediate-risk subgroup, the 70-gene signature could be useful to decide in elderly patients whether they may benefit from adjuvant chemotherapy or not. Conventional clinicopathological factors were not suitable for a prediction of the 70-gene signature results in these patients.

Background

The purpose of this study was to investigate the clinicopathological features and analyze the prognostic factors of triple-negative breast cancer (TNBC).

Patients and Methods

The clinical data of 1,788 breast cancer patients was collected and analyzed. The Kaplan-Meier method was used to estimate survival. Multivariate analysis of the prognostic factors for survival was performed using the Cox regression model.

Results

Patients with TNBC exhibited characteristics significantly differing from those with non-TNBC. There was a higher proportion of patients with age < 35 years, stage III disease, tumor size > 5 cm, lymph node positivity, and histological grade 3. The 5-year disease-free survival (DFS) rates of TNBC and non-TNBC patients were 75.7 and 79.6%, respectively (p < 0.05). 5-year overall survival (OS) was 86.6 and 93.5%, respectively (p < 0.05). In multivariate Cox regression analysis, the independent prognostic factors for shorter DFS were age < 35 years (hazard ratio (HR) 2.105), positive lymph nodes (HR 7.039), histological grade 3 (HR 1.841), and for shorter OS positive lymph nodes (HR 4.626).

Conclusion

The proportion of TNBC in breast cancer in China is higher than in other areas. TNBC is correlated with younger age, larger tumor size, positive lymph nodes, higher clinical stage and histological grade, and lower DFS and OS, which is consistent with previous reports.

Background

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.

Case Report

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.

Conclusion

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.

Background

The aim of our study was to analyze diagnostic results, different treatment modalities, and the outcome of patients with breast abscesses treated at our institution in a multi-modality breast team, to determine whether minimally invasive treatments are successful.

Methods

110 patients with mastitis and suspected breast abscesses at our institution between January 2000 and end of September 2007 were retrospectively analyzed. Abscesses were diagnosed using ultrasonography (US), and the material obtained using US-guided fine needle aspiration (FNA) was further examined.

Results

29% of the patients were treated conservatively with antibiotics only, 51% were treated with US-guided FNA or drainage placement. 11% of the patients underwent additional surgery after minimally invasive treatment (i.e. conversion rate). 9% of the patients underwent primary surgery. Early complications occurred in 7% of patients treated minimally invasive but not in patients treated with surgery alone. Late complications occurred in 5% of patients who underwent minimally invasive treatments and in 30% of patients who underwent surgery.

Conclusions

US-guided FNA as a minimally invasive therapy in combination with antibiotics was found to successfully treat most breast abscesses and, in cases where a larger volume of pus was involved, the placement of an additional drainage catheter was effective.

Background

Many studies about the adjuvant endocrine therapy of postmenopausal patients with hormone receptor-positive breast cancer have shown significant superiority of aromatase inhibitors (AIs) compared to tamoxifen only. Within these studies, different AIs (anastrozole, letrozole, exemestane) and treatment strategies (upfront, switch, extended adjuvant) were applied.

Material and Methods

The intention of our enquiry was to evaluate the implementation of the results of these studies in German breast cancer centers and university hospitals. Questionnaires were sent to 200 breast cancer centers and university hospitals (returns: 108).

Results

Our enquiry showed that most centers preferred anastrozole as upfront therapy in patients with an intermediate or high risk of relapse. Furthermore, during AI therapy, additional bisphosphonate treatment was applied ‘always’ in only 9% of cases, and in 78% of cases of proved osteopenia/osteoporosis. Surprisingly, 50% of the participating centers do not exclude AIs in premenopausal women.

Conclusion

At the time of our enquiry, anastrozole as upfront therapy was consistent with the recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) from 2009. Compared to tamoxifen, AIs increase the risk of osteoporosis, which can, however, be prevented and treated with concomitant bisphosphonate therapy. The rare use of bisphosphonates as well as contraindicated AI therapy in premenopausal patients show amongst others the substantial need for more information.

Background

The growth inhibitory effect of tamoxifen is used for the treatment of breast cancer. Tamoxifen efficacy is mediated by its biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoenzyme, to the active metabolite endoxifen. We investigated the relationship of CYP2D6 genotypes to the metabolism of dextromethorphan (DM), which is frequently used as a surrogate marker for the formation of endoxifen.

Methods

The CYP2D6 genotype was determined by polymerase chain reaction (PCR) in previously untreated patients with hormone receptor-positive invasive breast cancer considered to receive antihormonal therapy. The DM/dextrorphan (DX) urinary excretion ratios were obtained in a subset of patients by high-pressure liquid chromatography (HPLC)-mediated urine analysis after intake of 25 mg DM. The relationships of genotype and corresponding phenotype were statistically analyzed for association.

Results

From 151 patients predicted based on their genotype data for the ‘traditional’ CYP2D6 phenotype classes poor, intermediate, extensive and ultrarapid, 83 patients were examined for their DM/DX urinary ratios. The genotype-based poor metabolizer status correlated with the DM/DX ratios, whereas the intermediate, extensive and ultrarapid genotypes could not be distinguished based on their phenotype. Citalopram intake did not significantly influence the phenotype.

Conclusions

The DM metabolism can be reliably used to assess the CYP2D6 enzyme activity. The correlation with the genotype can be incomplete and the metabolic ratios do not seem to be compromised by citalopram. DM phenotyping may provide a standardized tool to better assess the CYP2D6 metabolic capacity.

Aim

To develop an immunomagnetic assay for the isolation of circulating tumor cells (CTCs) followed by the analysis of a multimarker panel, which will enable the characterization of these malignant cells with high accuracy.

Patients and Methods

Peripheral blood (PB) was collected from 32 metastatic breast cancer patients and 42 negative controls. The antibodies BM7 and VU1D9 were used for immunomagnetic tumor cell enrichment. A real-time reverse transcription-polymerase chain reaction (RT-PCR) approach for the markers KRT19, SCGB2A2, MUC1, EPCAM, BIRC5 and ERBB2 was used for CTC detection and characterization.

Results

The positivity rates for each marker were as follows: 46.9% for KRT19, 25.0% for SCGB2A2, 28.1% for MUC1, 28.1% for EPCAM, 21.9% for BIRC5, and 15.6% for ERBB2. After the creation of individualized cutoffs, the sensitivity and specificity of the combined marker gene panel increased to 56.3% and 100%, respectively. Interestingly, 27.0% of the HER2-negative tumor patients showed ERBB2 mRNA-positive CTCs.

Conclusions

The described technique can be used to measure CTCs with great accuracy. The use of a multimarker panel for the characterization of CTCs may provide real-time information and be of great value in therapy monitoring.

At the first Austrian multidisciplinary expert panel on controversies in local treatment of breast cancer, 22 experts of all relevant disciplines discussed current areas of debate (surgery of the breast, surgery and pathology of the axilla, reconstructive surgery, radiotherapy, and imaging) in local therapy. The most controversial area of debate was the area of axillary surgery. The panel agreed that it was no longer necessary to perform completion axillary lymph node dissection (ALND) when micrometastases are diagnosed in the sentinel lymph node. The only prospective trial comparing patients with sentinel node macrometastases with or without completion ALND had to be terminated early due to failure in sufficient patient recruitment. As long as the frequently discussed issues have not been solved and in light of the lack of any clear level 1 evidence, the panel decided not to recommend omitting axillary dissection in patients with 1 or 2 macrometastases meeting the inclusion criteria of the ACOSOG Z0011 trial. The Austrian panel similarly decided not to recommend omitting axillary dissection in patients with macrometastases and low-risk breast cancer in general. These decisions reflect the increasing skepticism of the scientific community against rapidly shifting paradigms without sufficient and clear evidence.

Background

Currently employed techniques for the localization of nonpalpable breast lesions suffer from various limitations. In this paper, we report on 2 patients in order to introduce an alternative technique, indocyanine green fluorescence-guided occult lesion localization (IFOLL), and determine its applicability for the surgical removal of this type of breast lesions.

Case Reports

Preoperatively, one of the patients had a needle biopsy-proven diagnosis of breast cancer, and the other one had suspicious findings for malignancy. Lesion localization was performed within 1 h before surgery under ultrasonography control by injecting 2 ml and 0.2 ml of indocyanine green into the lesion and its subcutaneous tissue projection, respectively. During surgery, the site of skin incision and the resection margins were identified by observing the area of indocyanine-derived fluorescence under the guidance of a near-infrared-sensitive camera. In both cases, the breast lesion was correctly localized, and the area of fluorescence corresponded well to the site of the lesions. Subsequent surgical excision was successful with no complications. On histopathologic examination, the surgical margins were found to be clear.

Conclusion

IFOLL seems to be a technically applicable and clinically acceptable procedure for the removal of nonpalpable breast cancer.

Background

Breast cancer is the most common cancer in women. Its prevalence is increasing annually by 2%. The determination of modifiable risk factors has been the subject of various studies. The aim of this study was to determine risk factors of breast cancer in women in Golestan Province.

Patients and Methods

This case-control study was conducted among women with breast cancer recorded in the cancer registry system between 2004 and 2006 (n = 134), and their age-matched healthy neighbors (n = 133). Data were statistically analyzed.

Results

Age at marriage, menarche and pregnancy, breast feeding, positive family history, marital status, and educational level were not significantly correlated with risk of breast cancer, but age at menopause (< 46.6 years) was significantly correlated (95% confidence interval 1.15–7.37; p = 0.021). Live births, still births, and infant deaths were not significantly different between the 2 groups. For other variables, such as smoking history, no odds ratio was calculated.

Conclusion

Results show that there is no significant correlation between variables and risk of breast cancer in our population, except for age at menopause. A large cohort study is recommended.

Background

Parotid gland metastasis in breast cancer is extremely rare, and only 14 cases have been reported between 1982 and 2010.

Case Report

A 67-year-old female patient was diagnosed with invasive lobular carcinoma of the left breast. Although clinical staging was T1N3M1 (stage IV), the tumor experienced a complete response to chemotherapy. We therefore performed a mastectomy followed by radiotherapy, and continued administration of trastuzumab. However, 11 months later, the patient complained of a swelling in the left parotid gland. Histology following a partial parotidectomy revealed a parotid gland metastasis from the breast.

Conclusion

Treatment with capecitabine in addition to trastuzumab, which is one of the strategies applied in HER2-positive breast cancer, was effective in our patient. Analysis of the 14 cases of parotid gland metastasis from the breast reported between 1982 and 2010 revealed that the metastasis may occur not by direct lymphatic but by hematogenous spread.

Background

Poland's syndrome is a rare congenital non-inherited anomaly that usually manifests itself during adolescence and is characterized by absence or deficient development of one of the breasts. To our knowledge, no case of breastfeeding after reconstruction surgery in patients with Poland's syndrome has been described.

Case Report

A 22-year-old female patient with Poland's syndrome underwent breast reconstruction. The procedure performed consisted of rotation of a myocutaneous flap harvested from the ipsilateral latissimus dorsi muscle, which was subsequently attached to the anterior thoracic wall to create a pouch and place a 300-ml round textured cohesive silicone gel-filled breast implant. 5 years later the patient got pregnant, and 1 year after delivery she is still breastfeeding normally with both breasts.

Conclusion

Reconstruction surgery with the latissimus dorsi muscle and a prosthesis was shown to be a potential and safe solution to achieve improvement of breast symmetry and to provide confidence and comfort in relation to self-image and, moreover, the ability to breastfeed.

Background

This study aimed to investigate the clinicopathological features and prognosis of operable breast cancers in young and elderly Chinese women.

Patients and Methods

This study included 209 patients aged ≤35 years and 213 patients aged ≥60 but <70 years, who received treatment between January 2000 and December 2004. The clinicopathological features, molecular subtypes, therapeutic strategies, and prognosis were evaluated.

Results

Tumor size was of significant difference between the 2 groups (p = 0.018), with more T2 and T3 tumors in the young group and more lymph node involvement in young patients with stage T1 tumors (p = 0.033). There were more triple-negative and less luminal A tumors in the young group (p = 0.018). 47.1% of tumors were not detected by mammography in the young group as compared to 5.5% in the elderly group (p < 0.001). More patients received chemotherapy in the young group (p < 0.001) and preferred breast-conserving surgery (p = 0.031). The 6-year disease-free survival (DFS) was 80 and 66% in the elderly and the young group, respectively (p = 0.001), but no difference was seen in overall survival.

Conclusions

Compared with elderly women, young breast cancer patients have different clinicopathological features and molecular subtypes, and poorer DFS. Furthermore, the insidious onset of breast cancer in young women suggests that clinicians should pay more attention to young women with breast abnormalities.

Some drugs are known for their fetal nephrotoxicity and should be avoided during pregnancy. We report on a pregnant woman suffering from breast cancer who received a weekly neoadjuvant trastuzumab (Herceptin®) therapy from 15 weeks of gestation onward, in addition to a 3-weekly carboplatin/docetaxel chemotherapy. Fetal renal insufficiency with anhydramnios and missing visualization of the fetal bladder developed at 21 weeks. After discontinuation of trastuzumab and repeated instillation of amniotic fluid, the amount of amniotic fluid remained stable after 24 weeks of gestation. After caesarean section at 34 weeks because of fetal growth restriction, the renal function of the neonate was normal postnatally. In accordance with the current literature, our case shows a reversible adverse effect of trastuzumab on the fetal renal function and confirms the current recommendation that trastuzumab in pregnancy should be avoided. In pregnancies exposed to trastuzumab, treatment should be discontinued and the fetus should be closely monitored, with particular attention to the amniotic fluid and the fetal bladder volume, as these reflect fetal renal function.

Breast cancer is the most prevalent malignant disease in women worldwide. Traditionally, surgical tumour resection was the primary step within the treatment algorithm of early stage disease; systemic therapy in order to reduce the rate of systemic recurrences followed. National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-18 found that pre- and postoperative administration of chemotherapy was equally effective. This study therefore established neoadjuvant chemotherapy as a valid treatment option, as the breast conservation rate is increased. Modern neoadjuvant regimens encompassing anthracyclines and taxanes yield pathological complete response (pCR) rates of around 20%, with higher efficacy observed in triple-negative tumours. The antibody trastuzumab is the first targeted agent established in neoadjuvant regimens for the treatment of Her2-positive breast cancer, as it raised pCR rates up to 50%. Novel approaches are aiming to increase the efficacy of neoadjuvant therapy. Inclusion of capecitabine might further increase pCR rates in selected patients, although data are not unanimous throughout the respective clinical trials. In patients harbouring BRCA-1 germline mutations, platinum derivatives are apparently promising. Novel Her2-targeted agents such as lapatinib and pertuzumab are currently under investigation in several clinical trials, while the role of bevacizumab, a monoclonal antibody inhibiting angiogenesis, awaits future clarification.

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.

Background

The aim of this study was to investigate the clinicopathologic characteristics, therapy methods, and prognosis of male breast cancer.

Patients and Methods

We retrospectively analyzed the clinicopathological characteristics, recurrence or metastasis, and survival information of 87 male breast cancer patients. Statistical analysis included the Kaplan-Meier method to analyze survivals, log-rank to compare curves between groups, and Cox regression for multivariate prognostic analysis. A p value of <0.05 was considered statistically significant.

Results

5-year disease free survival (DFS) and 5-year overall survival (OS) were 66.3 and 77.0%, respectively. Monofactorial analysis showed tumor size, stage, lymph node involvement, and adjuvant chemotherapy to be prognostic factors with regard to 5-year DFS and 5-year OS. Multivariate Cox regression analysis showed tumor size, stage, and adjuvant chemotherapy to be independent prognostic factors with regard to 5-year DFS and 5-year OS.

Conclusion

Male breast cancer has a lower incidence rate and poor prognosis. Invasive ductal carcinoma is the main pathologic type. Operation-based combined therapy is the standard care for these patients. Tumor size, stage, and adjuvant chemotherapy are independent prognostic factors. More emphasis should be placed on early diagnosis and early therapy, and adjuvant chemotherapy may improve survival.

Background

Inverted nipples are a common problem and a challenging clinical condition to repair. Multiple methods have been reported to correct inverted nipples, most of which will destroy breastfeeding function.

Patients and Methods

We have designed a simple nipple retractor to correct inverted nipples. A total of 53 patients with 95 inverted nipples underwent an operation in which the nipples were retracted into a normal position and fixated with the nipple retractor and wires under local anesthesia. Nipple retractors were to be worn for 6 months. Postoperatively, the patients were invited to follow-up on the 1st day, the 7th day, after 1 month, 3 months and 6 months, and yearly thereafter. Wire adjustments were performed as needed. Mean follow-up was 11.9 months (range 8–18 months).

Results

Improvement occurred in all patients and was sustained in all cases throughout the follow-up period. The total complication rate was 5.26% (5/95). The main complications included depigmentation (2.11%, 2/95), areolar ulcer (2.11%, 2/95), and wire dislocation (1.05%, 1/95).

Conclusion

The nipple retractor is a simple tool with which severely inverted nipples can be successfully corrected with a low complication rate. Close follow-up and careful postoperative care are important to avoid complications.

Background

Thrombotic microangiopathy (TMA) is defined as thrombocytopenia and microangiopathic hemolytic anemia. Cancer-associated TMA, a rare but fatal condition, seems an entity distinct from classical thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS).

Patients and Methods

All patients with breast cancer-associated TMA treated at our institution between 2003 and 2008 were analyzed retrospectively. To elucidate pathophysiological mechanisms, we measured the serum activity of the metalloprotease ADAMTS13.

Results

8 patients were identified. All showed bone marrow infiltration of breast cancer as well as thrombocytopenia, schistocytes, and hemolytic anemia. ADAMTS13 activity was mildly decreased in 4/6 patients (20–108%, normal range 30–120%), but none showed severely low levels as is characteristic of classical TTP. 6 patients were treated with anthracycline-containing fractionated chemotherapy, 5/6 patients experienced partial response. Overall survival was 13 months. Fractionated chemotherapy was well tolerated.

Conclusions

Cancer-associated TMA has an underlying mechanism different from classical TTP. While bone marrow infiltration might be of major relevance, ADAMTS13 deficiency seems to be an epiphenomenon. Fractionated chemotherapy resulted in higher remission rates and comparatively long survival.

Recently reported data from the German ZORO trial and the Italian PROMISE-GIM6 trial have come to different conclusions. The AGO Breast Commission does not recommend the general use of luteinizing hormone-releasing hormone (LHRH) analogues for the preservation of ovarian function. Instead, we distinguish between patients with hormone receptor-negative and hormone receptor-positive disease. This article reviews the AGO recommendations in light of the ZORO and PROMISE-GIM6 data. In conclusion, separate recommendations are needed for the prevention of ovarian failure and for fertility preservation because the trials did not investigate fertility rate as a primary outcome measure. The results from not yet published trials such as OPTION and POEM may shed new light on the role of LHRH analogues.

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.