Jacobus J.M. van der Hoeven

Bio: Jacobus J.M. van der Hoeven is an academic researcher from Leiden University. The author has contributed to research in topics: Medicine & Breast cancer. The author has an hindex of 15, co-authored 22 publications receiving 2594 citations. Previous affiliations of Jacobus J.M. van der Hoeven include Erasmus University Rotterdam & Johns Hopkins University.

70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer

Abstract: BackgroundThe 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical–pathological criteria in selecting patients for adjuvant chemotherapy. MethodsIn this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the...

Biologic correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography

Abstract: PURPOSE: Variable uptake of the glucose analog 18fluorodeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especia...

Gene Expression Profiling to Identify the Histogenetic Origin of Metastatic Adenocarcinomas of Unknown Primary

Abstract: Purpose Patients with adenocarcinoma of unknown primary origin (ACUP) constitute approximately 4% of all malignancies. For effective treatment of these patients, it is considered optimal to identify the primary tumor origins. Currently, the success rate of the diagnostic work-up is only 20% to 30%. Our goal was to evaluate the contribution of gene expression profiling for routine clinical practice in patients with ACUP. Patients and Methods Formalin-fixed, paraffin-embedded (FFPE) samples were obtained from 84 patients with a known primary adenocarcinoma and from 38 patients with ACUP. An extensive immunohistochemical panel classified 16 of the patients with ACUP, whereas 22 patients remained unclassified for their histogenetic origin. Information about staging procedures and clinical follow-up were available in all patient cases. The expression data were analyzed in relation to clinicopathologic variables and immunohistochemical results. Results The gene expression–based assay classified the primary site...

Determinants of diagnostic performance of [F-18]fluorodeoxyglucose positron emission tomography for axillary staging in breast cancer.

Abstract: Objective To prospectively investigate determinants of the accuracy of staging axillary lymph nodes in breast cancer using [F-18]fluorodeoxyglucose positron emission tomography (FDG PET). Methods Patients with primary operable breast cancer underwent FDG PET of the chest followed by sentinel node biopsy (SNB, n = 47) and/or complete axillary lymph node dissection (ALND, n = 23). PET scans were independently interpreted by three observers in a blinded fashion with respect to the FDG avidity of the primary tumor and the axillary status. The results were compared to histopathological analyses of the axillary lymph nodes. Clinicians were blinded to the PET results. Results Axillary lymph node specimens and FDG PET scans were evaluated in 70 patients (59% cT1). Overall, 32 (46%) had lymph node metastases as established by SNB (18/47) or ALND (14/23), 20 of which were confined to a single node. The overall sensitivity of FDG PET was 25%, with a specificity of 97%. PET results were false-negative in all 18 positive SNBs and true-positive in 8/14 in the ALND group. The performance of FDG PET depended on the axillary tumor load and the FDG avidity of the primary tumor. Intense uptake in the primary tumor was found in only 57% of the patients, and this was independent of the size. There was excellent interobserver agreement of visual assessment of FDG uptake in primary tumor and axillary lymph nodes. Conclusions The sensitivity of FDG PET to detect occult axillary metastases in operable breast cancer was low, and it was a function of axillary tumor load and FDG avidity of the primary tumor. Even though the clinical relevance of occult disease detected by SNB needs to be confirmed, it is suggested that FDG PET in these patients should be focused on exploiting its nearly perfect specificity and the potential prognostic relevance of variable FDG uptake.

Why do cancers have high aerobic glycolysis

Abstract: If carcinogenesis occurs by somatic evolution, then common components of the cancer phenotype result from active selection and must, therefore, confer a significant growth advantage. A near-universal property of primary and metastatic cancers is upregulation of glycolysis, resulting in increased glucose consumption, which can be observed with clinical tumour imaging. We propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions. However, upregulation of glycolysis leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity. Subsequent cell populations with upregulated glycolysis and acid resistance have a powerful growth advantage, which promotes unconstrained proliferation and invasion.

From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors

Abstract: The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with 18 F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0. Methods: PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors’ experience, draft criteria were formulated for PET tumor response to treatment. Results: Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has

Breast Cancer Treatment: A Review.

Abstract: Importance Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer. Observations Breast cancer is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerlyHER2): hormone receptor positive/ERBB2 negative (70% of patients),ERBB2positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). More than 90% of breast cancers are not metastatic at the time of diagnosis. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Triple-negative breast cancer is more likely to recur than the other 2 subtypes, with 85% 5-year breast cancer–specific survival for stage I triple-negative tumors vs 94% to 99% for hormone receptor positive andERBB2positive. Systemic therapy for nonmetastatic breast cancer is determined by subtype: patients with hormone receptor–positive tumors receive endocrine therapy, and a minority receive chemotherapy as well; patients withERBB2-positive tumors receiveERBB2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy; and patients with triple-negative tumors receive chemotherapy alone. Local therapy for all patients with nonmetastatic breast cancer consists of surgical resection, with consideration of postoperative radiation if lumpectomy is performed. Increasingly, some systemic therapy is delivered before surgery. Tailoring postoperative treatment based on preoperative treatment response is under investigation. Metastatic breast cancer is treated according to subtype, with goals of prolonging life and palliating symptoms. Median overall survival for metastatic triple-negative breast cancer is approximately 1 year vs approximately 5 years for the other 2 subtypes. Conclusions and Relevance Breast cancer consists of 3 major tumor subtypes categorized according to estrogen or progesterone receptor expression andERBB2gene amplification. The 3 subtypes have distinct risk profiles and treatment strategies. Optimal therapy for each patient depends on tumor subtype, anatomic cancer stage, and patient preferences.