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Biomedical subjects

J L Peterse

Publications and source records attributed to J L Peterse.

At least 19 recordsLinked to original sources
PubMed2006

The correlation of mammographic-and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls.

Breast cancers in BRCA1 gene mutation carriers often have specific histologic features: grade III tumors with pushing margins. Our purpose was to compare the mammographic and histologic features of breast cancers in carriers with those in age-matched sporadic controls. The features of breast cancers in 27 BRCA1 carriers found during annual surveillance were compared to those in 107 age-matched sporadic controls. The carriers had no (classic) spiculated mammographic lesions, a high percentage of well-defined masses and hardly any masses with microcalcifications, whereas the controls had significantly fewer well-defined ones and only in 27% spiculated lesions on the mammogram. The well-defined mammographic tumors correlated in 83% of the carriers and in 70% of the controls with histologic circumscribed tumor margins. Spiculated mammographic lesions in the controls were in 90% grade I or II tumors. DCIS with or without infiltration was seen in 22% of the carriers and in 45% of the controls. In conclusion, breast cancers diagnosed in BRCA1 carriers do not have classic malignant mammographic features. A minority of the young sporadic controls show the classic malignant lesion on the mammogram. Both carriers and controls generally show a good correlation between their mammographic- and histologic tumor pattern.

Adult↗
PubMed2006

The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast.

AIM: To report the incidence and predictive value of positive axillary nodes in ductal carcinoma in situ (DCIS) and T1a carcinoma of the breast. METHODS: Cases from The Netherlands Cancer Institute were used to determine the incidence of lymph-node metastases. All consecutive patients with primary breast cancer that were treated between 1989 and 1998 and who had undergone axillary dissection were selected. Patients were identified with pure DCIS (n = 71), DCIS with small invasion (n = 12), invasive ductal/lobular carcinoma (IDC/ILC) < or =5 mm (n = 18) or tubular carcinoma < or =10 mm (n = 17). All archived lymph nodes of these patients were re-evaluated using immunohistochemistry (IHC). RESULTS: In DCIS the incidence increased from 1.4% with routine staining to 11% with IHC. For DCIS with small invasion it was 0 vs 27%, respectively. In IDC/ILC sized 2-5 mm the incidence rose from 6 to 12% and in tubular carcinoma < or =10 mm from 0 to 12%. All but one of the immunohistochemically detected metastases were isolated tumour cells (n = 9) or small (micro)metastases (n = 4). Maximally two nodes per patient were affected. None of the patients with positive lymph nodes died during follow-up (mean 102 months). CONCLUSIONS: Survival of our patients appeared not to be influenced by the finding of micrometastases in the lymph nodes by IHC. Immunohistochemistry of the sentinel node seems not contributive to further treatment in these patients.

Adenocarcinoma↗
PubMed2006

Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer.

BACKGROUND: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. PATIENTS AND METHODS: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil, epirubicin and cyclophosphamide) followed by radiation therapy and tamoxifen, or the same treatment but with high-dose alkylating chemotherapy (cyclophosphamide, thiotepa and carboplatin) replacing the fifth course of FEC. Of these patients, 621 had HER2/neu-negative disease, as determined by immunohistochemistry and chromogenic in situ hybridisation. RESULTS: At a median follow-up of 84 months, a trend for a better relapse-free survival was observed in the high-dose arm: (hazard ratio (HR) 0.84, P = 0.076, two-sided). The 621 patients with HER2/neu-negative disease benefited from high-dose therapy, while patients with HER2/neu-positive disease did not (test for interaction, P = 0.006). There was a marked relapse-free survival benefit for patients with HER2/neu-negative disease (71.5% versus 59.1%, 5 years after randomisation; HR 0.68, P = 0.002) and also a survival benefit (78.2% versus 71.0% at 5 years; HR 0.72, P = 0.02). CONCLUSIONS: The findings from this subgroup analysis provide additional evidence that HER2/neu-positive breast cancer is relatively resistant to alkylating agents. For HER2/neu-negative tumours, however, high-dose chemotherapy should remain the subject of clinical studies.

Antineoplastic Agents, Alkylating↗
PubMed2005

No common denominator for breast cancer lymph node metastasis.

The axillary lymph node status is the most powerful prognostic factor for breast cancer patients to date. The molecular mechanisms that control lymph node metastasis, however, remain poorly understood. To define patterns of genes or gene regulatory pathways that drive breast cancer lymph node metastasis, we compared the gene expression profiles of 15 primary breast carcinomas and their matching lymph node metastases using microarrays. In general, primary breast carcinomas and lymph node metastases do not differ at the transcriptional level by a common subset of genes. No classifier or single gene discriminating the group of primary tumours from those of the lymph node metastases could be identified. Also, in a series of 295 breast tumours, no classifier predicting lymph node metastasis could be developed. However, subtle differences in the expression of genes involved in extracellular-matrix organisation and growth factor signalling are detected in individual pairs of matching primary and metastatic tumours. Surprisingly, however, different sets of these genes are either up- or downregulated in lymph node metastases. Our data suggest that breast carcinomas do not use a shared gene set to accomplish lymph node metastasis.

Adult↗
PubMed2005

Long-term prognosis of patients with local recurrence after conservative surgery and radiotherapy for early breast cancer.

We have studied the long-term prognosis of 266 patients considered to have isolated local recurrence in the breast following conservative surgery and radiotherapy for early breast cancer. The median follow-up of the patients still alive after diagnosis of local relapse was 11.2 years. At 10 years from the date of salvage treatment, the overall survival rate for the 226 patients with invasive local recurrence was 39% (95% CI, 32-46), the distant recurrence-free survival rate was 36% (95% CI, 29-42), and the local control rate (i.e., survival without subsequent local recurrence or local progression) was 68% (95% CI, 62-75). Among patients with a local recurrence at or near the original tumour site a better distant disease-free survival was observed for patients with recurrences measuring 1cm or less, compared to those with larger recurrences. This suggests, though does not prove, that early detection of local recurrence can improve the treatment outcome but might as well point towards a different biologic behaviour, facilitating early detection.

Adult↗
PubMed2005

Changing patterns in diagnosis and treatment of ductal carcinoma in situ of the breast.

BACKGROUND: The increased incidence of ductal carcinoma in situ (DCIS) of the breast and the emergence of new diagnostic and therapeutic tools like mammographic screening, stereotactic core biopsy and reconstructive surgery prompted us to investigate how these developments influenced diagnosis and treatment. METHODS: Clinical and pathological characteristics of 403 patients with DCIS consecutively treated at The Netherlands Cancer Institute between 1986 and 2002 were evaluated and the effect of introduction of mammographic screening, stereotactic core biopsy and reconstruction on diagnosis and treatment was studied. RESULTS: Following the nationwide introduction of mammographic screening the number of non-symptomatic DCIS increased from 47 to 77%. Introduction of stereotactic core biopsy resulted in a rise of one-step procedures from 26 to 52%. Mastectomy rate did not change over time: 59% overall. However, reconstruction rate increased from 17 to 39%. CONCLUSION: This study shows a steep rise in diagnosis of non-symptomatic DCIS after introduction of screening. Further, the introduction of pre-operative diagnosis by stereotactic core biopsy resulted in a decrease of multiple surgical procedures. Mastectomy, with increasing application of breast reconstructions, remains an important treatment modality in the management of DCIS despite advancements in detection and diagnosis.

Adult↗
PubMed2005

Expression of oestrogen receptor and loss of E-cadherin are diagnostic for gastric metastasis of breast carcinoma.

AIMS: To investigate whether immunohistochemical staining for oestrogen receptor (ER)alpha, progesterone receptor (PgR) and E-cadherin might be useful to differentiate between metastatic breast carcinoma and primary gastric carcinoma. METHODS: Gastric biopsies of 75 patients containing adenocarcinoma were stained for ERalpha, PgR and E-cadherin. Included were: Group A, 28 patients with primary gastric cancer; Group B, 28 patients with an adenocarcinoma containing gastric biopsy and a clinical diagnosis of metastatic breast carcinoma; Group C, all consecutive patients with a positive gastric biopsy in 2001 (n = 19) without clinical history of breast carcinoma and not followed by gastric resection (control group). RESULTS: All ERalpha+ or PgR+ carcinomas (n = 20) were of patients with a previous or concurrent history of breast carcinoma: 19 in group B, one in group C. In addition, absence of E-cadherin staining was seen significantly more often in patients with metastatic breast carcinoma than in patients with primary gastric cancer (P < 0.001). CONCLUSION: Positive immunohistochemical staining for ERalpha or PgR of an adenocarcinoma in a gastric biopsy is diagnostic for metastatic breast carcinoma. Moreover, when carcinoma in a gastric biopsy is negative for E-cadherin staining, metastatic breast carcinoma should be considered.

Adenocarcinoma↗
PubMed2004

[Detailed pathological examination of the sentinel lymph nodes in order to detect micrometastases: no clinical relevance in patients with breast cancer].

Staging of the axillary lymph nodes yields important prognostic information in patients with breast cancer. The characteristics of the primary tumour are more significant for prognosis if only micrometastases (diameter < or = 2.0 mm) are found. For staging purposes and to estimate the prognosis, pathological examination of axillary lymph nodes therefore need not be focused on the detection of micrometastases. Sentinel lymph node biopsy is increasingly being used as an alternate staging method and to determine the indication for axillary lymph node dissection. To reduce the risk of overlooking lymph node metastasis, the sentinel node is being more thoroughly investigated, resulting in the finding of micrometastases in 10-20% of sentinel node negative patients. The sentinel node tumour load correlates with the chance of detecting more metastases in the axilla: an average of 18% for micrometastases, 12% for submicrometastases (diameter < or = 0.2 mm). However, if detailed pathological examination of the sentinel node is omitted, this would result in a low false-negative percentage (1.1-2.5% of all patients undergoing a sentinel node examination), which is less than the percentage false negatives in the sentinel lymph node procedure itself (3.2% on average). Hence, the benefit of detailed pathologic examination with step sectioning and the application of immunohistochemical staining may be doubted.

Axilla↗
PubMed2004

Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

Breast Neoplasms↗
PubMed2004

Diagnostic accuracy for different strategies of image-guided breast intervention in cases of nonpalpable breast lesions.

To find out whether ultrasound-guided fine-needle aspiration (FNA) and ultrasound and stereotactic-guided large core needle biopsy (LCNB) are reliable alternatives to needle-localised open breast biopsy (NLBB) in daily practice, we performed a retrospective study and evaluated the validity of these methods. In all, 718 women with 749 nonpalpable breast lesions from three Dutch Hospitals were included, and the validity of the various methods for diagnosis was assessed. This was carried out according to a method described by Burbank and Parker for evaluating the quality of an image-guided breast intervention. We compared our results with the outcome of the COBRA study. Overall, all diagnostic strategies (NLBB, FNA, LCNB ultrasound and stereotactic guided) show comparable agreement rates. However, the miss rates differ: 2% for NLBB, 3% for COBRA (LCNB in study setting), 5% for FNA and 8-12% for LCNB in practice. Fine-needle aspiration was nonconclusive in 29%, and shows an overestimation for DCIS in 9%. The DCIS underestimate rate in NLBB was 8%. For the assessment of lesions consisting of microcalcifications only and to exclude malignancy in all other lesions, a 14-gauge needle should be used. Ultrasound-guided intervention can be performed in a large percentage of nonpalpable lesions. Lesions consisting only of microcalcifications on mammography need special attention.

Adult↗
PubMed2004

Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology.

AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

Biomarkers, Tumor↗
PubMed2003

[The treatment of ductal carcinoma in situ (DCIS) of the breast].

Ductal carcinoma in situ (DCIS) of the breast is diagnosed more and more often in the Netherlands as a result of mammographic population screening and improved mammography techniques. Mastectomy and local excision, with or without radiotherapy, are used for the treatment of DCIS, but breast-conserving therapy seems a logical option in view of the favourable prognosis. Radiotherapy following total excision of DCIS reduces the local recurrence rate by half. Incomplete excision of DCIS is associated with a higher rate of local recurrence, which is invasive in about 50% of the cases and can therefore affect the prognosis adversely. There are conflicting opinions in the literature as to which patients with DCIS can be treated with breast-conserving therapy and whether local excision should be followed by radiotherapy, as is the case for breast-conserving treatment of invasive mammary carcinoma. The diagnosis and treatment of DCIS are therefore complex and require a multidisciplinary approach. Patients may be selected for breast-conserving therapy on the basis of diagnostic characteristics and risk factors.

Breast Neoplasms↗
PubMed2003

The influence of tamoxifen treatment on the oestrogen receptor in metachronous contralateral breast cancer.

Adjuvant tamoxifen treatment reduces the occurrence of contralateral breast cancer (CBC). The aim of the study was to investigate the hypothesis that adjuvant tamoxifen reduces the occurrence of oestrogen-receptor (ER)-positive CBC, but not the growth of ER-negative CBCs, and to examine survival after diagnosis of CBC. For the study, ER status was immunohistochemically assessed in CBCs of 35 tamoxifen-treated patients and 115 patients without previous hormonal treatment. Cases were retrieved from a series of patients treated from 1984 to 1995 at nine hospitals. The interval between ipsi- and contralateral breast cancer was at least 1 year. It was seen that the proportion of patients with an ER-negative CBC was significantly higher among those with prior tamoxifen treatment: 37% vs 18% (P=0.047). No difference between the two groups in overall and disease-specific survival following CBC was found. However, the stage differed for both groups: tamoxifen users more often had node-positive contralateral disease (P= 0.045). In conclusion, metachronous CBCs developing after 1-3 years of tamoxifen treatment are more often ER-negative breast cancers. So far this does not seem to have a major impact on survival.

Aged↗
PubMed2003

Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome.

The aim of this study was to provide a better insight into breast cancer response to chemotherapy. Chemotherapy improves outcome in breast cancer patients. The effect of cytotoxic treatment cannot be predicted for individual patients. Therefore, the identification of tumour characteristics associated with tumour response and outcome is of great clinical interest. We studied 97 patients, who received anthracycline-based neoadjuvant chemotherapy. Tumour samples were taken prior to and after chemotherapy. We quantified the response to chemotherapy clinically and pathologically and determined histological and molecular tumour characteristics. We assessed changes in the expression of Bcl-2, ER, P53 HER2 and Ki-67. Association with response and outcome was tested for all parameters. The experimental results showed 15 clinical (17%) and three (3%) pathological complete remissions. There were 18 (20%) clinical vs 29 (33%) pathological nonresponders. The expression of most markers was similar before and after chemotherapy. Only Ki-67 was significantly decreased after chemotherapy. Factors correlated with response were: large tumour size, ER negativity, high Ki-67 count and positive P53 status. Tumour response and marker expression did not predict disease-free or overall survival. In conclusion, clinical and pathological response assessments are poorly associated. Proliferation decreases significantly after chemotherapy. ER negativity and a high proliferation index are associated with better response. HER2 status does not predict response, and outcome is not related to tumour response.

Adult↗
PubMed2003

Reduction in the number of sentinel lymph node procedures by preoperative ultrasonography of the axilla in breast cancer.

Currently, breast cancer patients without clinically suspicious lymph nodes are candidates for sentinel lymph node procedures (SLNPs). The aims of this study were to investigate whether preoperative axillary ultrasonography and fine-needle aspiration cytology (FNA) can reduce the number of the more time-consuming SLNPs, and to identify a subset of quantitative nodal features to predict metastatic involvement. 268 axillae were ultrasonographically examined. FNA was performed on suspicious nodes (smallest diameter > or =5 mm or atypical cortex appearance). SLNP was omitted if a tumour-positive node was found on FNA. Length, width, maximum cortex thickness and appearance of cortex and hilus were ultrasonographically established. In 93 axillae (35%), at least one node was detected with ultrasound. FNA was performed once per axilla on 66 nodes; 37 (56%) contained tumour cells. 31% of all tumour-positive axillae (macro-+micrometastases) was found by ultrasound and FNA (37/121). 41% of all axillae containing macrometastases was found by ultrasound and FNA (36/87). SLNPs were reduced by 14% (37/268). Maximum cortex thickness is the main feature to predict metastatic involvement (area under Receiver Operating Characteristic (ROC) curve (A(Z))=0.87).

Adult↗
PubMed2003

Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.

Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

Breast Neoplasms↗