[Predictors of the Utilization and Waiting Period Before Starting an Oncological Rehabilitation after Breast Cancer]. / Prädiktoren der Inanspruchnahme und des Beginns einer onkologischen Rehabilitation nach Brustkrebs.

PURPOSE: This study explores the sociodemographic, medical and work-related factors leading to a participation in an in-house rehabilitation measure after primary treatment for breast cancer. METHODS: The prospective multi-center study is based on a written survey with employed breast cancer patients who were recruited at 11 breast cancer centers in Lower Saxony, Germany. Predictors of participation were examined by logistic regression, predictors of the time period before starting the rehabilitation by linear regression. RESULTS: 409 patients returned their questionnaires at all three time-points. Response rates were 80,1% 3 weeks after surgery (t0), 95,2% 6 months after surgery (t1) and 89,9% one year after surgery (t2). Altogether, 294 patients (72%) participated in the rehabilitation measure. Respondents, 90% of whom participated in rehabilitation before returning to work, began their rehabilitation on average 21 weeks after primary surgery. They showed an increased probability of participation if they had indicated the need to clarify their job situation (OR=2,74, p<0,01), or if their answers displayed a detrimental relation between effort and reward at work (OR=3,89, p<0,05). At the same time, higher age, a higher level of school education (OR=4,23) and reduced physical health (OR=0,94, p<0,01) increased the chance for breast cancer patients to take part in oncological rehabilitation. The starting point of rehabilitation was only predictable by medical treatments: adjuvant chemotherapy (ß=0,492, p≤0,001), additional surgery (ß=0,112, p<0,05), and radiation therapy within the second half year after primary surgery (ß=0,20; p<0,001) led to a postponement. CONCLUSION: This study shows that an increased need of breast cancer patients for medical and socio-psychological support leads to their participation in an in-house rehabilitation and thus underlines the necessity of these institutions. Women with an impaired psychological health should be given extra attention.

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients.

BACKGROUND: Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766). METHODS: AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER), and HER2 were considered. RESULTS: Patients with higher AURKA expression had a shorter metastasis-free survival (MFS) in the Mainz (HR 1.93; 95% CI 1.34 - 2.78; P < 0.001), Rotterdam (HR 1.95; 95% CI 1.45- 2.63; P<0.001) and Transbig (HR 1.52; 95% CI 1.14-2.04; P=0.005) cohorts. AURKA was also associated with MFS in the molecular subtype ER+/HER2- carcinomas (HR 2.10; 95% CI 1.70-2.59; P<0.001), but not in ER-/HER2- nor in HER2+ carcinomas. In the multivariate Cox regression adjusted to age, grade and tumor size, AURKA showed independent prognostic significance in the ER+/HER2- subtype (HR 1.73; 95% CI 1.24-2.42; P=0.001). Prognosis of patients in the highest quartile of AURKA expression was particularly poor. In addition, AURKA correlated with the proliferation metagene (R=0.880; P<0.001), showed a positive association with grade (P<0.001), tumor size (P<0.001) and HER2 (P<0.001), and was inversely associated with ER status (P<0.001). CONCLUSIONS: AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile) have a particularly bad prognosis and may profit from therapy with AURKA inhibitors.

First Prospective Cross-Sectional Study on the Impact of Immigration Background and Education in Early Detection of Breast Cancer.

BACKGROUND: Although immigrant health is an important issue in national health policy, there is a serious shortage of data in many countries. Most studies lack information on educational status, which is a major limitation. This prospective cross-sectional study analyzed a real-world breast cancer population on the influence of immigration background and educational status on participation in breast cancer early detection programs in the federal state of Lower Saxony, Germany. METHODS: Data collection was conducted from 2012 to 2016 in six certified breast cancer centers using a standardized questionnaire for patients' interview and tumor-specific data from the patients' medical records. RESULTS: 2,145/3,047 primary breast cancer cases were analyzed. 17.5% of our patients had a history of immigration, including n = 202 first-generation immigrants and n = 168 second-generation immigrants. Most of them were citizens of EU27 member states. No significant difference was seen in age, tumor stage, histology, grading, Ki-67, Her2/neu-status, and hormone receptor status compared to the native cohort. 100% participation rate in the breast cancer early detection programs were seen in patients with no school graduation. With regards to the national mammography screening program, participation decreased significantly with educational status (p = 0.0003). CONCLUSIONS: No tumor biological differences were seen between immigrants and German natives. In first-generation immigrants, early detection programs were well accepted despite sociocultural and language differences. Participation rate decreased significantly with higher education levels irrespective of country of origin. Immigration background does not have a negative effect on the participation in breast cancer screening. This mainly relates to immigrants from EU27 member states.

Prognostic effect of epithelial cell adhesion molecule overexpression in untreated node-negative breast cancer.

PURPOSE: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. EXPERIMENTAL DESIGN: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. RESULTS: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disease-free survival independent of age, pT stage, histologic grade, estrogen receptor (ER), progesterone receptor (PR), as well as HER2 status (P = 0.028; hazard ratio, 1.60; 95% confidence interval, 1.05-2.44). Recently, so-called triple-negative (HER-2, ER, and PR) breast cancer has received increased attention. We noticed a similar association of Ep-CAM with disease-free survival in the triple-negative group as for the entire cohort. CONCLUSION: In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer. This suggests that Ep-CAM may be a well-suited target for specific therapies particularly in HER-2-, ER-, and PR-negative tumors.

Influence of resection volume on locoregional recurrence of breast cancer after breast-conserving surgery.

BACKGROUND: The goals of breast-conserving surgery are to provide the survival equivalent of mastectomy, a cosmetically acceptable breast and a low rate of locoregional recurrence in the treated breast. This retrospective study investigated the impact of the resection volume on locoregional recurrence after breast-conserving therapy in patients with early-stage invasive breast cancer. PATIENTS AND METHODS: Retrospective data from 185 women who were treated for operable breast tumours by breast-conserving surgery between 1995-1999 at the Martin-Luther-University in Halle/Germany were included in our study. Extent of total resection volume (TRV), tumour volume (V) and difference volume (DV) was compared for the influence on locoregional recurrence. RESULTS: Our data showed no significant correlation between the risk of locoregional recurrence and the extent of resection volume. Predictors of an increased risk of locoregional recurrence after breast-conserving surgery were large primary tumour, grading, lymphatic vascular invasion, hormone receptor status and lack of radiotherapy or hormonal therapy. CONCLUSION: According to the accuracy of locoregional disease control and maintenance of the breast's shape, our results support conservative surgery in early-stage breast cancer followed by radiotherapy and adjuvant systemic therapy.

Prognostic impact of haemoglobin levels in breast cancer.

BACKGROUND: Many patients with solid tumours suffer from anaemia, as a consequence of the disease itself or its treatment. Anaemia affects the quality of life and can have a negative impact on overall survival. The aim of the current study was to analyse the impact of haemoglobin levels on the prognosis of patients with primary breast cancer. PATIENTS AND METHODS: Retrospective data from 249 women treated for operable breast tumours were included in our study. Haemoglobin (Hb) levels independently of anticancer therapy were compared for the prognostic influence on disease-free and overall survival. RESULTS: A significant correlation between higher minimum Hb level during chemotherapy and the disease-free and overall survival was found. Pre-treatment haemoglobin levels had no prognostic influence on the disease-free and overall survival. CONCLUSION: The present data showed that anaemia during adjuvant chemotherapy to be a negative prognostic indicator for survival of patients with breast cancer.

Analysis of a RECQL splicing mutation, c.1667_1667+3delAGTA, in breast cancer patients and controls from Central Europe.

RECQL is a DNA helicase required for genomic stability. Two studies have recently identified RECQL as a novel breast cancer susceptibility gene. The most common RECQL mutation, the 4 bp-deletion c.1667_1667+3delAGTA, was five-fold enriched in Polish breast cancer patients, but the exact magnitude of the risk is uncertain. We investigated two hospital-based breast cancer case-control series from Belarus and Germany, respectively, comprising a total of 2596 breast cancer patients and 2132 healthy females. The mutation was found in 9 cases and 6 controls, with an adjusted Odds Ratio 1.23 (95% CI 0.44-3.47; p = 0.69) in the combined analysis. Among the cases, heterozygosity for c.1667_1667+3delAGTA was linked with estrogen-receptor positive breast cancer. There was no significant difference in age at diagnosis between carriers and non-carriers, and only one of the carriers reported a first-degree family history. Meta-analysis with the initial study from Poland suggests an about two-fold increase in risk for this mutation (OR 2.51; 95% CI 1.13-5.57, p = 0.02). Altogether, the data indicate that RECQL* c.1667_1667+3delAGTA is not a high-risk mutation for breast cancer though it could represent a moderate-risk breast cancer susceptibility allele. Further studies will be required to determine the clinical significance of testing for this RECQL mutation.

Histological analysis of silicone breast implant capsules and correlation with capsular contracture.

BACKGROUND: A study was undertaken to investigate long-term histological changes in the environment of breast implants and their correlation with complains at the time of capsular contracture defined by the Baker score. METHOD: The collagenous capsules of 53 silicone breast implants from 43 patients (23 smooth and 30 textured devices) were evaluated histologically for capsular thickness, the presence of histiocytes, the amount of silicone and calcification in the capsule, and the presence of synovial-like metaplasia of the inner surface of the capsule with light microscopy and polarised light. All parameters were correlated with the Baker score. RESULTS: A significantly higher degree of the Baker score was found with increasing patient age (p<0.001), implant duration (p<0.02), and capsular thickness (p<0.009). A trend towards greater capsular thickness was documented in patients who had a breast augmentation for cosmetic reasons. Synovial-like metaplasia was seen in 28 capsules (52.8%). The highest incidence was found in textured implants with a duration of less than 5 years. Histiocytic inflammation was more common in patients with clinical symptoms (p<0.001) and around subglandular implants (p<0.096). CONCLUSIONS: The histological findings of breast capsules were related to: the nature of the device surface (smooth versus textured), implant duration, and the degree of capsular contracture. Capsular contracture (Baker score of 3 or 4) was related to implant duration, capsule thickness, patient age, and inflammation.

The value of positron emission tomography in the follow-up for breast cancer.

BACKGROUND: The aim of this study was to investigate the diagnostic value of FDG PET in the follow-up for breast cancer in disease-free patients and patients suspected of having recurrent or metastatic disease. As a single imaging tool, PET can be compared with the conventional diagnostic means used for different examination sites. PATIENTS AND METHODS: A total of 73 PET studies were carried out on 57 patients who had been diagnosed as having breast cancer. Sixteen patients had two PET scans. Thirty-eight scans (52.%) were performed in a follow-up setting. Thirty-five PET scans were performed in patients suspected of having recurrent disease or elevated tumor marker. Depending on the region of suspicion, conventional imaging included computed tomography, magnetic resonance imaging, chest X-ray, ultrasound and X-ray. All the patients in our study were followed-up for a period of 12 months. RESULTS: PET correctly identified metastatic or recurrent disease in 25 out 27 cases of clinical suspicion. In patients examined because of elevated tumour marker CA 15-3, PET was able to detect recurrence or metastatic disease in six of the eight patients. The absence of disease was correctly diagnosed by PET in 35 out of 38 scans in 24 patients in the follow-up for breast cancer. The overall sensitivity and specificity for PET was 80.6% and 97.6%, respectively. On the basis of a yearly rate of disease progression of 5-8%, the mean positive predictive value was 74.5% and the mean negative predictive value 98.3%. CONCLUSION: PET has been shown to have impact on the staging and management of recurrent or metastatic breast cancer in cases of suspicion and in a follow-up setting. The current oncological situation can be clarified with a single basic imaging modality.

Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach.

Noninvasive biomarkers are urgently needed for early detection of breast cancer since the risk of recurrence, morbidity and mortality are closely related to disease stage at the time of primary surgery. In the past decade, many proteomics-based approaches were developed that utilize the protein profiling of human body fluids or identification of putative biomarkers to obtain more knowledge on the effects of cancer emergence and progression. Herein, we report on an analysis of proteins in the tear fluid from breast carcinoma patients and healthy women using a de novo proteomic approach and 25 mixed samples from each group. This study included 25 patients with primary invasive breast carcinoma and 25 age-matched healthy controls. We performed a MALDI-TOF-TOF-driven semi-quantitative comparison of tear protein levels in cancer (CA) and control (CTRL) using a de novo approach in pooled samples. Over 150 proteins in the tear fluid of CTRL and CA were identified. Using an in-house-developed algorithm we found more than 20 proteins distinctly upregulated or downregulated in the CTRL and CA groups. We identified several proteins that had modified expression in breast cancer patients. These proteins are involved in host immune system pathways (e.g., C1Q1 or S100A8) and different metabolic cascades (ALDH3A or TPI). Further validation of the results in an independent population combined with individual protein profiling of participants is needed to confirm the specificity of our findings and may lead to a better understanding of the pathological mechanism of breast cancer.

Dual-plane implant positioning for capsular contracture of the breast in combination with mastopexy.

OBJECTIVE: This study aims at combined surgical therapy options concerning patients with a clinically relevant and long-established capsular contracture following subglandular breast augmentation in a glandular ptotic breast. METHODS: This is a review of 23 patients with capsular contracture. Three patients had a revision surgery for capsular contracture and implant dislocation before. The mean implant duration in the case of the twenty patients without any previous revision was 96 months. A revision implant has been re-located in a dual-plane position and further corrective surgery was carried out to adapt the glandular ptotic breast. Between 2001 and 2003, a chart review was performed on all patients for capsular contracture and ptotic breast by using the technique presented in this study. RESULTS: In each case, the operation was performed as a one-stage procedure. The procedure included the following steps: Removal of the implant and total capsulectomy, preparation of an inferior de-epithelialised skin pedicle above the inframammary crease, release of the inferior origins of the pectoralis major muscle, creation of a new implant pocket by continuous connection of the inferior muscle border with the cranial edge of the inferior skin pedicle (dual-plane), adaptation of the soft-tissue/skin envelope by closing the cranial V over the implant coverage, preservation of the areola by creating a cranial or cranial medial pedicle. There was a follow-up for a period of up to 48 months, and any complication that occurred was documented. At follow-up period, all patients who had been implanted with a new implant pocket were free of a clinically relevant capsular contracture. CONCLUSIONS: In the cases of a severe capsular contracture and glandular-ptotic breasts, we presented the surgical corrections of the parenchyma/skin envelop as a one-stage procedure following the establishment of a new implant pocket.

Positron emission tomography scanning in gynecologic and breast cancers.

PURPOSE OF REVIEW: Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose represents a noninvasive functional imaging modality that is based on metabolic characteristics of malignant tumors. The recent findings of this technique in breast cancer, cervical cancer, ovarian cancer, and other gynecologic malignancies are discussed. RECENT FINDINGS: In breast cancer, positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose is more accurate than conventional methods for the staging of distant metastases, enables early assessment of treatment response in patients undergoing primary chemotherapy. The diagnostic accuracy for axillary lymph node staging depends on the tumor load of the lymph nodes. The sensitivity of this technique in detecting primary breast cancer is limited in small breast lesions and invasive lobular cancer. In cervical cancer it is the most accurate noninvasive method for lymph node staging and it can accurately depict recurrent ovarian cancer in patients with elevated CA125 levels. False negative findings in well differentiated adenocarcinoma and borderline lesions as well as false positive findings in benign conditions limit the role of positron emission tomography scanning for the differential diagnosis of adnex tumors. SUMMARY: Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose reveals unique information about tumor metabolism in gynecologic malignancies and breast cancer. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the early assessment of treatment response in breast cancer and the detection of recurrent disease in ovarian cancer. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance.

FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast cancer.

Breast cancer continues to be one of the most common cancers in North America and Western Europe. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG PET) represents a non-invasive functional imaging modality that is based on metabolic characteristics of malignant tumours. In breast cancer, FDG PET is more accurate than conventional methods for staging of distant metastases or local recurrences and enables early assessment of treatment response in patients undergoing primary chemotherapy. Recent data indicate a rationale for the use of FDG PET in cases of asymptomatically elevated tumour marker levels in the presence of uncertain results of conventional imaging. Despite the fact that PET cannot rule out microscopic disease, it does have particular value in providing, in a single examination, a reliable assessment of the true extent of the disease. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the assessment of asymptomatic patients with elevated tumour marker levels. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance.

Ki67, HSP70 and TUNEL for the specification of testing of silicone breast implants in vivo.

This investigation of capsular tissue adjacent to silicone breast implants concerns the long-term tissue response to the implant environment. Fifty-three silicone breast implants have been analyzed at the time of explantation. The implant duration ranged from 2 months to 153 months. The reason for explantation was capsular contracture (57%), dissatisfaction with the effect (11%), local inflammation (6%), implant rupture (4%) and exchange of tissue expanders (21%). The cell turnover within the interface of the silicone device and the fibrous capsule was detected by specific antibodies against Ki67 for cell proliferation, by TUNEL for apoptosis, and by DNA strand breaks and heat shock protein 70 (HSP70) for cell stress. We found a negative correlation between the expression of HSP 70 and the capsular thickness (p < 0.043) and decreased levels in specimens obtained from Baker IV implant capsules. Ki67, and TUNEL were significantly positive (p < 0.001 for both) and HSP 70 were significantly negative (p < 0.001) with signs of inflammation. Both Ki67 and TUNEL indicated decreasing values over time. Ki67 and TUNEL showed no correlation with clinical signs of implant failure, such as the Baker score. The expression of HSP70, on the other hand, was connected with structural changes of the implant capsule, in terms of capsular thickness and the Baker score.

Anal sphincter injury during vaginal delivery--an argument for cesarean section on request?

AIMS: Fear of damage to the pelvic floor from vaginal delivery and long-term sequelae (urinary and anal incontinence) sometimes being cited as an indication for cesarean section on request. The aim of the present study was to compare the effects of vaginal delivery versus elective cesarean section on anal sphincter function. MATERIAL AND METHODS: We studied 71 consecutive women six weeks before delivery, 52 of them 4-6 weeks after delivery, and all patients with occult sphincter lesions 3 months after delivery. A bowel function questionnaire was completed, and anal endosonography, manometry, and measurement of the pudendal-nerve terminal motor latency were performed. RESULTS: Forty-two (80.8 percent) patients were delivered vaginally, ten (19.2 percent) by elective cesarean section at term. Clinically recognized anal sphincter injuries occurred in 9.5 percent (4) of patients, two of them developed incontinence for gas. The overall incidence of anal incontinence after vaginal delivery was 4.8 percent. Occult sphincter defects were identified endosonographically in 19 percent (8) of women, there was no reported case of any anal incontinence 3 months after delivery. No woman delivered by cesarean section had altered anal continence or any significant change in anal pressures, rectal sensibility, and PNTML. CONCLUSION: Severe sphincter tear is the single most important factor leading to anal incontinence in women, whereas occult sphincter defects are rarely associated with short-term sequelae, but may predispose to the development of anal incontinence later on in life. Elective cesarean section should be recommended for women at increased risk for anal incontinence.