Expression of cell adhesion molecules and prognosis in breast cancer.

BACKGROUND: Cell adhesion molecules (CAMs) play an important role in the process of metastasis. The prognostic value of tumour expression of N-cadherin, E-cadherin, carcinoembryonic antigen (CEA) and epithelial CAM (Ep-CAM) was evaluated in patients with breast cancer. METHODS: A tissue microarray of the patient cohort was stained immunohistochemically for all markers and analysed by microscopy. Expression was classified into two categories, with the median score as cut-off level. For CEA, the above-median category was further subdivided in two subgroups based on staining intensity (low or high intensity). RESULTS: The cohort consisted of 574 patients with breast cancer with a median follow-up of 19 years. Below-median expression of E-cadherin (P = 0·015), and above-median expression of N-cadherin (P = 0·004), Ep-CAM (P = 0·046) and CEA (P = 0·001) all resulted in a shorter relapse-free period. Multivariable analysis revealed E-cadherin and CEA to be independent prognostic variables. Combined analysis of CEA and E-cadherin expression showed a 3·6 times higher risk of relapse for patients with high-intensity expression of CEA, regardless of E-cadherin expression, compared with patients with below-median CEA and above-median E-cadherin tumour expression (hazard ratio 3·60, 95 per cent confidence interval 2·12 to 6·11; P < 0·001). An interaction was found between expression of these two CAMs (P < 0·001), suggesting a biological association. CONCLUSION: Combining E-cadherin and CEA tumour expression provides a prognostic parameter with high discriminative power that is a candidate tool for prediction of prognosis in breast cancer.

Quality of life in relation to tamoxifen or exemestane treatment in postmenopausal breast cancer patients: a Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial side study.

Tamoxifen and aromatase inhibitors are associated with side effects which can significantly impact quality of life (QoL). We assessed QoL in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial and compared these data with reported adverse events in the main database. 2,754 Dutch postmenopausal early breast cancer patients were randomized between 5 years of exemestane, or tamoxifen (2.5-3 years) followed by exemestane (2.5-2 years). 742 patients were invited to participate in the QoL side study and complete questionnaires at 1 (T1) and 2 (T2) years after start of endocrine treatment. Questionnaires comprised the EORTC QLQ-C30 and BR23 questionnaires, supplemented with FACT-ES questions. 543 patients completed questionnaires at T1 and 454 patients (84%) at T2. Overall QoL and most functioning scales improved over time. The only clinically relevant and statistically significant difference between treatment types concerned insomnia; exemestane-treated patients reported more insomnia than tamoxifen-treated patients. Discrepancy was observed between QoL issue scores reported by the patients and adverse events reported by physicians. Certain QoL issues are treatment- and/or time-specific and deserve attention by health care providers. There is a need for careful inquiry into QoL issues by those prescribing endocrine treatment to optimize QoL and treatment adherence.

Patients' needs and preferences in routine follow-up for early breast cancer; an evaluation of the changing role of the nurse practitioner.

BACKGROUND: In evaluating follow-up of early breast cancer, patients' views on care are important. The aim of this study was to evaluate the effect of the introduction of nurse practitioners (NPs) in a breast cancer unit on patients' informational needs, preferences and attitude towards follow-up. PATIENTS AND METHODS: A cross-sectional survey was performed among two groups in 2005. Group A (n = 89) consisted of patients operated before, and group B (n = 100) after the introduction of a breast cancer unit (respectively in 1998-1999 and 2001-2004). RESULTS: Response was 72% in group A and 84% in group B. Median follow-up was 69 (54-86) and 33 (0-57) months, respectively. Aspects highly appreciated by patients in both groups were lifetime follow-up, information about prognosis, life style and additional investigations. Important discussion subjects were fatigue, pain, genetic factors, prevention and arm function/lymph-oedema. Less valued aspects were information about peers, conversations with psychologists or social workers, breast reconstruction, and acceptation by family members. The informational needs and preferences did not differ statistically significantly between both groups. In group B, communication with the caregiver was valued higher and more patients indicated that the caregiver took the time needed. More patients in group B indicated that follow-up could be performed by the NP. Duration of follow-up correlated with preferred frequency, not with informational needs in follow-up, only young age increased these needs. CONCLUSION: Despite the limitations of this retrospective study, we conclude that while expectations and informational needs did not change with the introduction of a NP to the standard care, patient satisfaction increased and communication and time taken were appreciated more.

Tailored follow-up for early breast cancer patients: a prognostic index that predicts locoregional recurrence.

AIMS: After treatment, early breast cancer patients undergo follow-up according to standard regimens. After the first year, the main goal is particularly to detect locoregional recurrences (LRR). Our aim was to develop a simple prognostic index to predict LRR to tailor the follow-up programme. METHODS: We used data from four large international clinical randomised trials and constructed the prognostic index using Cox proportional hazards regression. The bootstrap (a resampling method) was used for internal validation. RESULTS: A total of 6516 patients treated according to current guidelines with complete covariable information were used for analysis. Covariables important for LRR in patients treated with breast conserving therapy were age, pathological tumour status, boost and surgical margins. The same variables were important for patients treated with a mastectomy, however, instead of the boost, the pathological nodal status was important. The index is composed to consist of three groups based on LRR risk after 10-years. CONCLUSIONS: We constructed a simple prognostic index that can be used to estimate risks of LRR in patients with early breast cancer. The prognostic index enables patients to be stratified into three subgroups with different outcomes with regard to LRR.

Variations in locoregional therapy in postmenopausal patients with early breast cancer treated in different countries.

BACKGROUND: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial is an international randomized trial evaluating the efficacy and safety of exemestane, alone or following tamoxifen. The large number of patients already recruited offered the opportunity to explore locoregional treatment practices between countries. METHODS: Patients were enrolled in Belgium, France, Germany, Greece, Ireland, Japan, the Netherlands, the UK and the USA. The core protocol had minor differences in eligibility criteria between countries, reflecting variations in national guidelines and practice regarding adjuvant endocrine therapy. RESULTS: Between 2001 and 2006, 9779 patients of mean(s.d.) age 64(9) years were randomized. Some 58.4 per cent had T1 tumours (range between countries 36.8-75.9 per cent; P < 0.001) and 47.3 per cent were axillary node positive (range 25.9-84.6 per cent; P < 0.001). Independent factors for type of breast surgery were country, age, tumour status and calendar year of surgery. After breast-conserving surgery, radiotherapy was given to 93.2 per cent of patients, 86.0 per cent in the USA and 100 per cent in France. Axillary lymph node dissection was performed in 82.0 (range 74.6-99.1) per cent. CONCLUSION: Despite international consensus guidelines, wide global variations were observed in treatment practices of early breast cancer. There should be further efforts to optimize locoregional treatment for breast cancer worldwide.

Maintenance of physical activity and body weight in relation to subsequent quality of life in postmenopausal breast cancer patients.

BACKGROUND: We prospectively examined the association between physical activity, body weight and quality of life in Dutch postmenopausal early breast cancer patients treated with adjuvant endocrine therapy. PATIENTS AND METHODS: In this side study of a large clinical trial, lifestyle and quality-of-life questionnaires were filled out 1 and 2 years after the start of endocrine therapy (T1 and T2, respectively) and included a pre-diagnosis lifestyle assessment (T0). A total of 435 breast cancer patients returned both questionnaires. RESULTS: Individuals with a physical activity level above the median who maintained this level from T0 to T1 reported the best global quality of life and physical functioning and the least fatigue at T2, as compared with individuals with low levels of physical activity which further decreased after diagnosis (difference of +16, +14, and -22 points on a 0-100 quality-of-life scale, respectively; P < 0.01). Overweight or obese women who gained body weight after diagnosis reported worst quality of life and most fatigue as compared with women who maintained a stable body weight (difference of -8, -10 and +2 points, respectively; P < 0.01). CONCLUSION: Maintaining high pre-diagnosis physical activity levels and a healthy body weight is associated with better quality of life after breast cancer.

Switching from tamoxifen to aromatase inhibitors for adjuvant endocrine therapy in postmenopausal patients with early breast cancer.

The third-generation aromatase inhibitors (AIs), including anastrozole, exemestane and letrozole, have demonstrated improved efficacy versus tamoxifen for the adjuvant endocrine treatment of postmenopausal patients with hormone receptor-positive breast cancer. AIs can be used in several adjuvant endocrine settings: as upfront therapy, switch to an AI after 2-3years of tamoxifen or extended therapy following 5years of tamoxifen. In the switch setting, two different types of study designs have been utilized. One is a late randomization design which randomizes patients who are disease-free after 2-3years of tamoxifen to receive an AI versus continuation of tamoxifen. In contrast, an early randomization design randomizes all patients immediately after primary treatment and prior to starting tamoxifen. Efficacy benefits with AIs have been shown in several trials evaluating the late randomization strategy, including the Intergroup Exemestane Study, the Italian Tamoxifen Anastrozole trial and the Anastrozole-Nolvadex 95 trial. Similarly, early randomization studies, including the Austrian Breast and Colorectal Cancer Study Group-8 and the Breast International Group (BIG) 1-98 trial, have demonstrated the effectiveness of receiving an AI after tamoxifen. Two trials are assessing an early switch strategy versus upfront AI therapy: the BIG 1-98 trial and the ongoing Tamoxifen Exemestane Adjuvant Multicentre trial are assessing switching from tamoxifen to an AI after 2-3years versus upfront AI therapy. This paper reviews studies that have investigated a switch strategy with AIs and considers the implications of these data on treatment choice for postmenopausal patients with hormone receptor-positive breast cancer.

Patterns of care in Dutch postmenopausal patients with hormone-sensitive early breast cancer participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

BACKGROUND: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial investigates the efficacy and safety of adjuvant exemestane alone and in sequence after tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. As there was a nationwide participation in The Netherlands, we studied the variations in patterns of care in the Comprehensive Cancer Centre Regions (CCCRs) and compliance with national guidelines. METHODS: Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. RESULTS: From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were < or =2 cm in 46% (within CCCRs 39%-50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%-100% of patients. Mastectomy was carried out in 55% (45%-70%), sentinel lymph node procedure in 68% (42%-79%) and axillary lymph node dissections in 77% (67%-83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%-70% of eligible patients (P < 0.001). DISCUSSION: In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement.

Validation study of the prognostic value of cyclin-dependent kinase (CDK)-based risk in Caucasian breast cancer patients.

In a Japanese study, cyclin-dependent kinase (CDK) based risk determined by CDK 1 and 2 activities was associated with risk of distance recurrence in early breast cancer patients. The aim of our study was to validate this risk categorization in European early breast cancer patients. We retrospectively analyzed frozen breast cancer specimens of 352 Dutch patients with histologically confirmed primary invasive early breast cancer. CDK-based risk was determined in tumour tissues by calculating a risk score (RS) according to kinases activity and protein mass concentration assay without the knowledge of outcome. Determination of CDK-based risk was feasible in 184 out of 352 (52%) tumours. Median follow-up of these patients was 15 years. In patients not receiving systemic treatment, the proportions of risk categories were 44% low, 16% intermediate, and 40% high CDK-based risk. These groups remained significant after univariate and multivariate Cox-regression analysis. Factors associated with a shorter distant recurrence-free period were positive lymph nodes, mastectomy with radiotherapy, and high CDK-based risk. There was no significant correlation with overall survival (OS). CDK-based risk is a prognostic marker of distance recurrence of patients with early breast cancer. More validation would be warranted to use of CDK-based risk into clinical practice.

[The advantages of preoperative systemic therapy in breast cancer]. / De voordelen van preoperatieve systemische therapie bij borstkanker.

Neoadjuvant systemic therapy is administered preoperatively in order to provide a better preparation for surgery by down sizing the tumour. A recent meta-analysis comparing neoadjuvant and adjuvant chemotherapy demonstrated a 17% (95% CI: 15.1-18.1) increase in breast-conserving operations with equal survival rates and maintenance of local control providing adequate surgery was performed. Comparable results have been reported with neoadjuvant hormonal therapy. However, in the case of hormonal therapy the tumour-shrinking effects persisted when treatment was sustained. Research has shown that the sentinel lymph node procedure continues to be reliable after neoadjuvant therapy. Therefore, axillary lymph node dissection is not necessary if the lymph node metastases have disappeared as a result of the neoadjuvant therapy: down staging. However, further research is needed to confirm the safety of this treatment approach. Assessment oftumour sensitivity during neoadjuvant therapy facilitates analysis of the prognostic value of tumour markers. The aim of this translational research is to provide better selection criteria to identify patients in which the systemic treatment will be beneficial.

[Acute sialoadenitis of the parotid gland]. / Acute sialoadenitis van de glandula parotidea.

An 88-year-old diabetic women was hospitalized because of a pheripheral vascular disorder. During her hospitalization she developed a right-sided facial swelling which was not limited by anatomical structures in this area. Ultrasound and computertomographic scanning supported the clinical diagnosis acute sialoadenitis of the parotid gland. The swelling resolved shortly after starting antibiotic therapy.

[Optimal adjuvant hormone therapy in postmenopausal women with hormone-sensitive mammary carcinoma: tamoxifen and the aromatase inhibitors anastrozole, exemestane and letrozole]. / Optimale adjuvante hormonale therapie bij postmenopauzale vrouwen met een hormoongevoelig mammacarcinoom: tamoxifen en de aromataseremmers anastrozol, exemestaan en letrozol.

Postmenopausal patients with hormone-sensitive breast cancer may be eligible for adjuvant hormone therapy. - For years, tamoxifen was the treatment of choice. - However, the side effects associated with tamoxifen, such as endometrial cancer and thromboembolic disorders, and the search for more effective agents have led to the introduction of new hormonal therapies. - The results of randomised trials with the third-generation aromatase inhibitors anastrozole, exemestane and letrozole demonstrate improved efficacy compared to tamoxifen. - Using aromatase inhibitors, the disease-free survival is prolonged and recent data from some studies also show a benefit in overall survival. - Aromatase inhibitors are associated with specific side effects consisting of osteoporosis/increased incidence of fractures and myalgia/arthralgia.

The preferred treatment for young women with breast cancer--mastectomy versus breast conservation.

Paradigms on breast cancer influence surgical treatment policies. Randomised trials that compared mastectomy with breast-conserving therapy (BCT) with adequate radiotherapy showed no difference in overall survival. However, after a long follow-up, BCT was associated with a higher local recurrence rate (up to four times higher). The EBCTCG meta-analysis of 2005 concluded that one breast cancer death can be avoided for four local recurrences avoided. A minority of breast cancer patients are younger than 40 years (6.5%). When confronted with the diagnosis of breast cancer, they potentially have a long lifespan. Therefore, it is crucial to avoid local recurrences. The following factors have a positive impact on local control: mastectomy (in stead of BCT), negative surgical margins and adjuvant treatment (radiotherapy and chemotherapy). In order to provide optimal local and systemic treatment for young patients, breast cancer requires a multidisciplinary approach and the patient has to be involved in the proper treatment decision. A predictive model is needed for doctors and patients to facilitate this process.

[The 4th large meta-analysis of all trials of the treatment of operable breast cancer: increased survival after a longer follow-up]. / De 4e grote meta-analyse op het gebied van operabel mammacarcinoom: meer overlevingswinst na langere follow-up.

The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) was founded in 1983. The EBCTCG coordinates the quinquennial worldwide meta-analyses of centrally located data on women in all randomised trials of early breast cancer. This 4th meta-analysis, with a follow-up of 15 years, showed an increased survival after the use of adjuvant hormonal or chemotherapy. The EBCTCG analyses have been responsible for major changes in the treatment of breast cancer in the past. However, we do not need another meta-analysis before implementing, for example, the improvement of chemotherapy with taxoids and the improvement of hormonal treatment with aromatase inhibitors. Nowadays, new treatments are implemented before the 5-year follow-up and are aimed more specifically at certain tumour characteristics.

[The multidisciplinary breast cancer care team: promoting better care]. / Het multidisciplinair mammateam: bevordering van goede zorg.

Breast cancer is the most commonly diagnosed form of cancer in women in the Western world. Various sorts of therapies are available and treatment plans are becoming more and more complex. The treatment of breast cancer is based on several prognostic and predictive factors, of which the TNM-classification is the best known. However, several new factors have been discovered and implemented over the past decade. As well as these, economic factors and doctor- and patient-related factors are also important. As a consequence of the multitude of factors and the ensuing complexity of treatment, it has become impossible for a single doctor to coordinate the complete treatment of a patient. Therefore, it seems obvious that patients with breast cancer should be managed by a breast cancer care team. Specialists and nurses from different disciplines are represented within this team, with the advanced practice nurse as the primary contact person. This type of team helps to lower mortality, improve quality of care and lower associated costs.

[Diagnostic image (236). A woman with acute unilateral swelling of the face]. / Diagnose in beeld (236). Een vrouw met acute enkelzijdige zwelling van het gelaat.

An 88-year-old woman developed right-sided facial swelling due to acute sialoadenitis of the parotid and submandibular glands.