Jakob de Vries

Obtaining Adequate Surgical Margins in Breast-Conserving Therapy for Patients with Early-Stage Breast Cancer: Current Modalities and Future Directions

Inadequate surgical margins represent a high risk for adverse clinical outcome in breast-conserving therapy (BCT) for early-stage breast cancer. The majority of studies report positive resection margins in 20% to 40% of the patients who underwent BCT. This may result in an increased local recurrence (LR) rate or additional surgery and, consequently, adverse affects on cosmesis, psychological distress, and health costs. In the literature, various risk factors are reported to be associated with positive margin status after lumpectomy, which may allow the surgeon to distinguish those patients with a higher a priori risk for re-excision. However, most risk factors are related to tumor biology and patient characteristics, which cannot be modified as such. Therefore, efforts to reduce the number of positive margins should focus on optimizing the surgical procedure itself, because the surgeon lacks real-time intraoperative information on the presence of positive resection margins during breast-conserving surgery. This review presents the status of pre- and intraoperative modalities currently used in BCT. Furthermore, innovative intraoperative approaches, such as positron emission tomography, radioguided occult lesion localization, and near-infrared fluorescence optical imaging, are addressed, which have to prove their potential value in improving surgical outcome and reducing the need for re-excision in BCT.

Identification and prediction of distress trajectories in the first year after a breast cancer diagnosis

OBJECTIVE In this article, we aim to (a) identify distinct trajectories of psychological distress in the first year after a breast cancer diagnosis in women treated with adjuvant therapy and (b) explore possible predictors of these trajectories, that is, demographic, medical, and personal characteristics. METHOD The 171 patients were assessed after diagnosis, after surgery, after adjuvant treatment, in the reentry phase, and in the (short-term) survivorship phase (2 and 6 months after the end of treatment, respectively). MAIN OUTCOME MEASURE Psychological distress was assessed with the 12-item General Health Questionnaire. RESULTS There were four trajectories of distress: a group that experienced no distress (36.3%), a group that experienced distress only in the active treatment phase (33.3%), a group that experienced distress in the reentry and survivorship phase (15.2%), and a group that experienced chronic distress (15.2%). Personality and physical complaints resulting from adjuvant treatment could distinguish the distress trajectories. Mastery was the only unique predictor. CONCLUSION Most patients were not distressed in response to breast cancer or only temporarily so. Yet, a minority of patients became or remained distressed after the end of treatment.

Extra-intestinal manifestations of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, which results from a germ line mutation in the APC (adenomatous polyposis coli) gene. FAP is characterized by the formation of hundreds to thousands of colorectal adenomatous polyps. Although the development of colorectal cancer stands out as the most prevalent complication, FAP is a multisystem disorder of growth. This means, it is comparable to other diseases such as the MEN syndromes, Von Hippel-Lindau disease and neurofibromatosis. However, the incidence of many of its clinical features is much lower. Therefore, a specialized multidisciplinary approach to optimize health care—common for other disorders—is not usually taken for FAP patients. Thus, clinicians that care for and counsel members of high-risk families should have familiarity with all the extra-intestinal manifestations of this syndrome. FAP-related complications, for which medical attention is essential, are not rare and their estimated lifetime risk presumably exceeds 30%. Affected individuals can develop thyroid and pancreatic cancer, hepatoblastomas, CNS tumors (especially medulloblastomas), and various benign tumors such as adrenal adenomas, osteomas, desmoid tumors and dental abnormalities. Due to improved longevity, as a result of better prevention of colorectal cancer, the risk of these clinical problems will further increase.We present a clinical overview of extra-intestinal manifestations, including management and treatment options for the FAP syndrome. Furthermore, we provide recommendations for surveillance of FAP complications based on available literature.

89Zr-Bevacizumab PET Imaging in Primary Breast Cancer

Vascular endothelial growth factor (VEGF)-A is overexpressed in most malignant and premalignant breast lesions. VEGF-A can be visualized noninvasively with PET imaging and using the tracer 89Zr-labeled bevacizumab. In this clinical feasibility study, we assessed whether VEGF-A in primary breast cancer can be visualized by 89Zr-bevacizumab PET. Methods: Before surgery, breast cancer patients underwent a PET/CT scan of the breasts and axillary regions 4 d after intravenous administration of 37 MBq of 89Zr-bevacizumab per 5 mg. PET images were compared with standard imaging modalities. 89Zr-bevacizumab uptake was quantified as the maximum standardized uptake value (SUVmax). VEGF-A levels in tumor and normal breast tissues were assessed with enzyme-linked immunosorbent assay. Data are presented as mean ± SD. Results: Twenty-five of 26 breast tumors (mean size ± SD, 25.1 ± 19.8 mm; range, 4–80 mm) in 23 patients were visualized. SUVmax was higher in tumors (1.85 ± 1.22; range, 0.52–5.64) than in normal breasts (0.59 ± 0.37; range, 0.27–1.69; P < 0.001). The only tumor not detected on PET was 10 mm in diameter. Lymph node metastases were present in 10 axillary regions; 4 could be detected with PET (SUVmax, 2.66 ± 2.03; range, 1.32–5.68). VEGF-A levels in the 17 assessable tumors were higher than in normal breast tissue in all cases (VEGF-A/mg protein, 184 ± 169 pg vs. 10 ± 21 pg; P = 0.001), whereas 89Zr-bevacizumab tumor uptake correlated with VEGF-A tumor levels (r = 0.49). Conclusion: VEGF-A in primary breast cancer can be visualized by means of 89Zr-bevacizumab PET.

Lymphatic mapping with intralesional tracer administration in breast carcinoma patients

The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary lymph node metastasis.

Sentinel node biopsy as a surgical staging method for solid cancers.

The sentinel node is the first lymph node that drains a primary tumour. If this lymphatic drainage occurs in a step-wise fashion, this lymph node reflects the pathological status of the remaining lymph node basin. The day before the operation, a total dose of 60 MBq 99mTc nanocolloid is injected around the primary tumour for lymphoscintigraphy. On the day of surgery, 1 ml of blue dye is injected around the primary tumour to facilitate sentinel lymph node detection. After making a small incision over the regional lymph node region, the sentinel node can be detected using a hand-held gamma ray detection probe; the sentinel lymph node and the afferent lymphatic vessels will be stained blue. Sentinel node biopsy has proved useful for malignant melanoma, breast cancer, penile cancer, vulvar cancer, Merkel cell carcinoma and thyroid cancer. New studies are described on breast cancer and malignant melanoma. Gamma-probe-guided localization of radiolabelled lymph nodes can direct the surgeon non-invasively to the exact location of the sentinel node. Once localized with a gamma probe, it is quick and easy to remove the sentinel node through a small incision. Discriminating the node from other tissue can be aided by blue dye which stains the lymph node. It appears that both radioactivity and blue dye are complementary for locating the sentinel node.

The Prognostic Effect of the Number of Histologically Examined Axillary Lymph Nodes in Breast Cancer: Stage Migration or Age Association?

BackgroundThe number of pathologically examined axillary nodes has been associated with breast cancer survival, and examination of ≥10 nodes has been advocated for reliable axillary staging. The considerable variation observed in axillary staging prompted this population-based study, which evaluated the prognostic effect of a variable number of pathologically examined nodes.MethodsIn total, 5314 consecutive breast cancer patients who underwent mastectomy or breast-conserving surgery and axillary dissection between 1994 and 1999 were included. The prognostic effect of the examined number of nodes was assessed with crude and relative survival analysis.ResultsA median number of 12 (range, 1–43) nodes were histologically examined, and 59% of the patients had no nodal tumor involvement. The number of examined nodes decreased with age (P < .001) and increased with tumor size (P < .001). Stratified for the number of tumor-positive nodes, overall survival seemed to be worse for patients with <10 compared with patients with ≥10 examined nodes (P < .001), whereas the relative survival did not differ. After adjusting for age, tumor size, number of positive nodes, and detection by screening in a multivariate analysis, the number of examined nodes was not associated with relative survival.ConclusionsThis study shows that the association between the number of pathologically examined axillary nodes and overall survival in node-negative and node-positive patients results from stage migration. The absence of an association between the number of examined nodes and relative survival further indicates that the association between the number of examined nodes and crude survival is confounded by age.

Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer: a phase I feasibility study

Purpose: To provide proof of principle of safety, breast tumor–specific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab–IRDye800CW targeting VEGF-A in patients with breast cancer. Experimental Design: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab–IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue. Results: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level. Conclusions: Our study shows that systemic administration of the bevacizumab–IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor margin uptake as evaluated by a systematic validation methodology. The findings are a step toward a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue. Clin Cancer Res; 23(11); 2730–41. ©2016 AACR.

Personal control over the cure of breast cancer: adaptiveness, underlying beliefs and correlates

Objectives: Although cognitive adaptation theory suggests that personal control acts as a stress buffer when facing adversity, maladaptive outcomes might occur when control is disconfirmed. The moderating effect of disappointing news on the adaptiveness of personal control over cure in women with breast cancer was examined and contrasted with the effect on the adaptiveness of general control over life. Additionally, the underlying beliefs and correlates of control over cure were explored.

The UICC/WHO-CCCE cancer education project : A different approach

The Union Internationale Contre le Cancer (UICC) and the WHO-Collaborating Centre for Cancer Education (WHO-CCCE) have started an international pilot project offering assistance to medical schools that want to implement in their curricula a two-week multidisciplinary cancer course aimed at cancer care in general practice. The approach will be bottom-up (based on the possibilities in individual medical schools) instead of top-down (based on general recommendations and rules established in published studies). In April 2000 one or more medical schools from each of four continents had registered. Registration is open to any medical school and to other schools that have satisfactory ongoing cancer courses. The aim is to develop a network among medical schools in order for them to learn from each others cancer education strategies and experiences.