Scalp cooling successfully prevents alopecia in breast cancer patients undergoing anthracycline/taxane-based chemotherapy.

INTRODUCTION: Chemotherapy for breast cancer induces alopecia, representing a major source of patient distress. This study assesses whether a scalp-cooling device is effective in reducing chemotherapy-induced alopecia, and assesses adverse treatment effects. MATERIALS AND METHODS: A prospective observational study including women with breast cancer undergoing chemotherapy and scalp cooling using a Paxman device. The primary efficacy end points were: successful hair preservation (no hair loss; <30% hair loss not requiring a wig; or <50% hair loss not requiring a wig) at the completion of chemotherapy. Secondary end points included adverse effects such as headache, pain, nausea or dizziness. RESULTS: The study enrolled 131 participants. Mean patient age was 49.8 years; 74% received anthracycline/taxane-based chemotherapy and 26% received taxane-monotherapy based chemotherapy. Hair preservation was successful in 102 women who underwent scalp cooling (71.0%; 95% CI = 63-79%). Only adverse events related to device use were collected, representing 7% (95% CI = 3-11%) of cases. CONCLUSIONS: Scalp cooling is effective in preventing hair loss among breast cancer patients undergoing standard chemotherapy treatment, and has minimal adverse effects.

Primary metastatic breast cancer in the era of targeted therapy - Prognostic impact and the role of breast tumour surgery.

BACKGROUND: Except for meeting the individual palliative need, the benefit of breast surgery in primary metastatic breast cancer (PMBC), also known as de novo metastatic breast cancer, on long-term outcomes remains controversial. Twenty-four hundred and one patients with metastatic breast cancer, enrolled between 2000 and 2011 in two prospective non-interventional studies on targeted therapy, were screened with respect to this question. METHODS: One study investigated trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in addition to mainly first-line chemotherapy. The other observed bevacizumab added to chemotherapy as first-line treatment for mostly HER2-negative disease. RESULTS: Five-hundred and seventy (24%) patients presented with PMBC, and valid information on resection of the primary tumour was available for 568 women. Out of these, 426 (75%) underwent local resection. The latter group was characterised by less overall metastatic burden and a lower proportion of T4 tumours. No major differences were observed with respect to age, hormone receptor and HER2 status, visceral disease and performance status. Numerically, the surgery group showed a slightly favourable progression-free survival (PFS, medians: 13.6 versus 11.8 months; P = 0.18) and overall survival (OS, 34.1 versus 31.7; P = 0.23). However, in multivariable analysis, including all other univariably significant parameters, no trend for better outcome after surgery remained detectable, neither for PFS (hazard ratio 0.99; P = 0.92) nor for OS (0.95; P = 0.71). CONCLUSIONS: Our findings suggest no major survival benefit for local resection in the overall PMBC population treated with modern targeted therapies. However, further analyses are warranted to define specific risk groups, which may benefit from surgical removal of the primary.

The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival.

AIMS: To evaluate how the St. Gallen intrinsic subtype classification for breast cancer surrogates predicts disease features, recurrence patterns and disease free survival. MATERIALS AND METHODS: Subtypes were classified by immunohistochemical staining according to St. Gallen subtypes classification in a 5-tyre system: luminal A, luminal B HER2-neu negative, luminal B HER2-neu positive, HER2-neu non luminal or basal-like. Data were obtained from the records of patients with invasive breast cancer treated at our institution. Recurrence data and site of first recurrence were recorded. The chi(2) test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between surrogates and clinicopathologic variables. RESULTS: A total of 2.984 tumors were classifiable into surrogate subtypes. Significant differences in age, tumor size, nodal involvement, nuclear grade, multicentric/multifocal disease (MF/MC), lymphovascular invasion, and extensive intraductal component (EIC) were observed among surrogates (p < 0.0001). After adjusting for confounding factors surrogates remained predictive of nodal involvement (luminal B HER2-neu pos. OR = 1.49 p = 0.009, non-luminal HER2-neu pos. OR = 1.61 p = 0.015 and basal-like OR = 0.60, p = 0.002) while HER2-neu positivity remained predictive of EIC (OR = 3.10, p < 0.0001) and MF/MC (OR = 1.45, p = 0.02). Recurrence rates differed among the surrogates and were time-dependent (p = 0.001) and site-specific (p < 0.0001). CONCLUSION: The St. Gallen 5-tyre surrogate classification for breast cancer subtypes accurately predicts breast cancer presenting features (with emphasis on prediction of nodal involvement), recurrence patterns and disease free survival.

Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study.

PURPOSE: To test whether combining bevacizumab, an anti-vascular endothelial growth factor treatment, with endocrine therapy (ET) could potentially delay the emergence of resistance to ET. PATIENTS AND METHODS: A multicenter, randomized, open-label, phase III, binational (Spain and Germany) study added bevacizumab (15 mg/kg every 3 weeks) to ET (ET-B; letrozole or fulvestrant) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 (HER2) -negative and hormone receptor-positive advanced breast cancer. We compared progression-free survival (PFS), overall survival (OS), overall response rate (ORR), response duration (RD), time to treatment failure (TTF), clinical benefit rate (CBR), and safety. RESULTS: From 380 patients recruited (2007 to 2011), 374 were analyzed by intent to-treat (184 patients on ET and 190 patients on ET-B). Median age was 65 years, 270 patients (72%) had Eastern Cooperative Oncology Group performance status of 0, 178 patients (48%) had visceral metastases, and 171 patients (46%) and 195 patients (52%) had received prior chemotherapy or ET, respectively. Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.06; P = .126). ORR, CBR, and RD with ET versus ET-B were 22% versus 41% (P < .001), 67% versus 77% (P = .041), and 13.3 months versus 17.6 months (P = .434), respectively. TTF and OS were comparable in both arms. Grade 3 to 4 hypertension, aminotransferase elevation, and proteinuria were significantly higher in the ET-B arm. Eight patients (4.2%) receiving ET-B died during study or within 30 days of end of treatment. CONCLUSION: The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer.

Trastuzumab in advanced breast cancer--a decade of experience in Germany.

BACKGROUND: Trastuzumab was registered in 2000 for the treatment of metastatic breast cancer, both as monotherapy and combination therapy with paclitaxel. In this prospective, non-interventional observation study, the 10-year experience with trastuzumab in the routine management of HER2-positive breast cancer was reviewed. METHODS: Between 2000 and 2010, 1843 evaluable patients with advanced HER2-positive breast cancer were recruited in 223 institutions across Germany. Patients were prospectively monitored for about one year. Additional information on long-term outcomes, progression-free survival (PFS), and overall survival (OS) were retrieved at several follow-up points. There were no restrictions with respect to diagnostic or therapeutic procedures. Patients were stratified into three cohorts depending on the treatment regimen, i.e. trastuzumab monotherapy (n=228, 12%), trastuzumab combined with chemotherapy (n=1346, 73%), or trastuzumab combined with endocrine therapy (n=269, 15%). RESULTS: Median age was 59.5 years with a proportion of 28% being older than 65 years. Over a maximum follow-up period of more than 10 years, 1538 PFS events were documented in 83% of patients, resulting in an estimated median PFS of 11.8 months. Median OS, based on recorded death in 64% of patients, amounted to 34.4 months, with 48% (95% confidence intervals 45-50%) still alive after three years. The subgroup selected for a treatment combination with endocrine drugs only had distinctly longer PFS and OS than the other two groups, achieving medians of 23.3 months and 56.3 months, respectively. Median PFS and OS in elderly patients over 65 years of age was 11.4 months and 28.3 months, respectively. Adverse reactions, including cardiac toxicity, of severity grade 3 or 4 were rare. CONCLUSIONS: The superior outcome of treatment strategies including trastuzumab in HER2 overexpressing breast cancer, proven in pivotal studies, was confirmed in the management of advanced breast cancer in Germany in the routine setting. Our data suggest a comparable clinical benefit of treatment with trastuzumab in elderly patients (>65 years), who are typically under-represented in randomized clinical studies.

Long-term tumor remission under trastuzumab treatment for HER2 positive metastatic breast cancer - results from the HER-OS patient registry.

BACKGROUND: In this study, we examined patients who had non-progressive disease for at least 2 years after diagnosis of inoperable locoregional recurrent or metastatic breast cancer under continuous trastuzumab treatment. Our primary goal was to assess the long-term outcome of patients with durable response to trastuzumab. METHODS: 268 patients with HER2-positive inoperable locally recurrent or metastatic breast cancer and non-progressive disease for at least 2 years under trastuzumab treatment were documented retrospectively or prospectively in the HER-OS registry, an online documentation tool, between December 2006 and September 2010 by 71 German oncology centers. The study end point was time to tumor progression. RESULTS: Overall, 47.1% of patients (95% confidence interval (CI): 39.9-54.1%) remained in remission for more than 5 years, while the median time to progression was 4.5 years (95% CI: 4.0-6.6 years). Lower age (<50 years) and good performance status (ECOG 0) at time of trastuzumab treatment initiation as well as complete remission after initial trastuzumab treatment were associated with longer time to progression. Interruption of trastuzumab therapy correlated with shorter time to progression. CONCLUSIONS: HER2-positive patients, who initially respond to palliative treatment with trastuzumab, can achieve a long-term tumor remission of several years.

Massive breast necrosis after extravasation of a full anthracycline cycle.

A 57-year-old woman with invasive breast cancer was referred for adjuvant chemotherapy after undergoing breast conservative therapy and axillary dissection. A port was inserted in the contralateral subclavian vein and epirubicin, cyclophosphamide and 5-fluorouracil was the treatment of choice. After the first cycle, the patient was sent home. The following day, she reported rapidly developing redness and pain in the right breast and diagnosis of epirubicin extravasation was made. She was hospitalised, the port was surgically removed and approximately two-thirds of the breast underwent tissue necrosis. The necrotic tissue was resected and a skin graft was harvested from the thigh. She was offered DIEP-flap reconstruction 8 months later. There were no complications, except for marginal necrosis of the flap. Necrosectomy was performed and resolved through an advancement flap.

The EndoPredict Gene-Expression Assay in Clinical Practice - Performance and Impact on Clinical Decisions.

The validated EndoPredict assay is a novel tool to predict the risk of metastases of patients with estrogen receptor positive, HER2 negative breast cancer treated with endocrine therapy alone. It has been designed to integrate genomic and clinical information and includes clinico-pathological factors such as tumor size and nodal status. The test is feasible in a decentral setting in molecular pathology laboratories. In this project, we investigated the performance of this test in clinical practice, and performed a retrospective evaluation of its impact on treatment decisions in breast cancer. During one year, EndoPredict assays from 167 patients could be successfully performed. For retrospective evaluation of treatment decisions, a questionnaire was sent to the clinical partner. Regarding the molecular EP class, samples from 56 patients (33.5%) had a low-risk, whereas 111 patients (66.5%) showed a high-risk gene profile. After integration of the clinicopathological factors the combined clinical and molecular score (EPclin) resulted in a low-risk group of 77 patients (46.4%), while 89 (53.6%) had a high risk EPclin score. The EPclin-based estimated median 10-year-risk for metastases with endocrine therapy alone was 11% for the whole cohort. The median handling time averaged three days (range: 0 to 11 days), 59.3% of the tests could be performed in three or less than three days. Comparison of pre- and post-test therapy decisions showed a change of therapy in 37.7% of patients. 16 patients (12.3%) had a change to an additional chemotherapy while 25.4% of patients (n = 33) changed to an endocrine therapy alone. In 73 patients (56.2%) no change of therapy resulted. In 6.1% of patients (n = 8), the patients did not agree to the recommendation of the tumor board. Our results show that the EndoPredict assay could be routinely performed in decentral molecular pathology laboratories and the results markedly change treatment decisions.

Identification of early molecular markers for breast cancer.

BACKGROUND: The ductal carcinoma in situ (DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma. Since DCIS is a curable disease, it would be highly desirable to identify molecular markers that allow early detection. Mice transgenic for the WAP-SV40 early genome region were used as a model for DCIS development. Gene expression profiling was carried out on DCIS-bearing mice and control animals. Additionally, a set of human DCIS and invasive mammary tumors were analyzed in a similar fashion. Enhanced expression of these marker genes in human and murine samples was validated by quantitative RT-PCR. Besides, marker gene expression was also validated by immunohistochemistry of human samples. Furthermore in silico analyses using an online microarray database were performed. RESULTS: In DCIS-mice seven genes were identified that were significantly up-regulated in DCIS: DEPDC1, NUSAP1, EXO1, RRM2, FOXM1, MUC1 and SPP1. A similar up-regulation of homologues of the murine genes was observed in human DCIS samples. Enhanced expression of these genes in DCIS and IDC (invasive ductal carcinoma) was validated by quantitative RT-PCR and immunohistochemistry. CONCLUSIONS: By comparing murine markers for the ductal carcinoma in situ (DCIS) of the mammary gland with genes up-regulated in human DCIS-samples we were able to identify a set of genes which might allow early detection of DCIS and invasive carcinomas in the future. The similarities between gene expression in DCIS and invasive carcinomas in our data suggest that the early detection and treatment of DCIS is of utmost relevance for the survival of patients who are at high risk of developing breast carcinomas.

Experiences with a specific screening instrument to identify psychosocial support needs in breast cancer patients.

OBJECTIVE: In order to determine the need for professional psychosocial support in breast cancer patients, we used the physician-administered Basic Documentation for Psycho-Oncology (PO-Bado), which is an expert rating scale containing 12 items belonging to somatic and psychological problems. Furthermore, we investigated sociodemographic and medical predictors of somatic and psychological distress and need for psychosocial support. STUDY DESIGN: From 2/2005 to 09/2007, n=333 consecutive patients with breast cancer were included in the study. The majority of the patients suffered from early-stage breast cancer. The mean age of the participants was 59.9 years (SD=12.6, range 24-92). Two physicians rated patients' psychosocial distress and evaluated their need for psychosocial support according to the PO-Bado guidelines. RESULTS: Exhaustion/tiredness was the item rated highest in the physical distress dimension. In the psychological distress dimension, the items anxiety/worries/tension and grief/despondency/depression obtained the highest mean. Younger age and a history of psychiatric/psychotherapeutic treatment in the past were associated with higher current distress. Women who planned to undergo mastectomy were rated as showing more somatic distress than women for whom breast conserving therapy was planned, but the two groups did not differ with regard to psychological distress. Objective cancer-related variables (tumour size and grading) were not associated with distress. Need for professional psychosocial support was seen in 23% of the patients. Previous psychiatric/psychotherapeutic treatment was the only variable associated with current need for psychosocial support. Forty-six percent of the patients with need for psychosocial support accepted the counselling offered. CONCLUSIONS: The structured assessment of breast cancer patients' psychosocial distress with the interviewer-administered PO-Bado assists the physician to arrive at a detailed expert evaluation. This might help to improve the psychosocial care of breast cancer patients.