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Biomedical subjects

H Peterse

Publications and source records attributed to H Peterse.

14 recordsLinked to original sources

Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer.

In the MRISC study, women with an inherited risk for breast cancer were screened by a 6-month clinical breast examination (CBE) and yearly MRI and mammography. We found that the MRISC screening scheme could facilitate early breast cancer diagnosis and that MRI was a more sensitive screening method than mammography, but less specific. In the current study we investigated the contribution of MRI in the early detection of breast cancer in relation to tumor characteristics. From November 1999 to October 2003, 1909 women were included and 50 breast cancers were detected, of which 45 were evaluable and included in the current study. We compared the characteristics of tumors detected by MRI-only with those of all other (non-palpable) screen-detected tumors. Further, we compared the sensitivity of mammography and MRI within subgroups according to different tumor characteristics. Twenty-two (49%) of the 45 breast cancers were detected by MRI and not visible at mammography, of which 20 (44%) were also not palpable (MRI-only detected tumors). MRI-only detected tumors were more often node-negative than other screen-detected cancers (94 vs. 59%; P=0.02) and tended to be more often <or=1 cm (58 vs. 31%; P=0.11). MRI was more sensitive than mammography for a wide spectrum of invasive tumor characteristics i.e., size, nodal status, histology, grade and ER status. Half of the breast cancers detected in this study were visible by MRI only and these tumors were smaller and significantly more often node-negative than other screen-detected tumors, suggesting that MRI makes an important contribution to the early detection of hereditary breast cancer.

Breast Neoplasms↗

The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma.

BACKGROUND: Cytokeratin immunohistochemistry (IHC) reveals a higher rate of occult lymph node metastases among lobular carcinomas than among ductal breast cancers. IHC is widely used but is seldom recommended for the evaluation of sentinel lymph nodes in breast cancer patients. OBJECTIVE: To assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes of patients with invasive lobular carcinoma. METHODS: The value of IHC, the types of metastasis found by this method, and the involvement of non-sentinel lymph nodes were analysed in a multi-institutional cohort of 449 patients with lobular breast carcinoma, staged by sentinel lymph node biopsy and routine assessment of the sentinel lymph nodes by IHC when multilevel haematoxylin and eosin staining revealed no metastasis. RESULTS: 189 patients (42%) had some type of sentinel node involvement, the frequency of this increasing with increasing tumour size. IHC was needed for identification of 65 of these cases: 17 of 19 isolated tumour cells, 40 of 64 micrometastases, and 8 of 106 larger metastases were detected by this means. Non-sentinel-node involvement was noted in 66 of 161 cases undergoing axillary dissection. Although isolated tumour cells were not associated with further lymph node involvement, sentinel node positivity detected by IHC was associated with further nodal metastases in 12 of 50 cases (0.24), a proportion that is higher than previously reported for breast cancer in general. CONCLUSIONS: IHC is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.

Axilla↗

Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer.

Inheritance of one defective BRCA2 allele predisposes humans to breast cancer. To establish a mouse model for BRCA2-associated breast cancer, we generated mouse conditional mutants with BRCA2 and/or p53 inactivated in various epithelial tissues, including mammary-gland epithelium. Although no tumors arose in mice carrying conditional Brca2 alleles, mammary and skin tumors developed frequently in females carrying conditional Brca2 and Trp53 alleles. The presence of one wildtype Brca2 allele resulted in a markedly delayed tumor formation; loss of the wildtype Brca2 allele occurred in a subset of these tumors. Our results show that inactivation of BRCA2 and of p53 combine to mediate mammary tumorigenesis, and indicate that disruption of the p53 pathway is pivotal in BRCA2-associated breast cancer.

Animals↗

Clinical presentation, endoscopic features, and treatment of gastric metastases from breast carcinoma.

BACKGROUND: Breast carcinoma is the most common malignancy in women. Metastatic involvement of the stomach is not well known. METHODS: Endoscopic features and treatment options were evaluated retrospectively for 51 patients with gastric metastases of breast carcinoma. RESULTS: The presenting sites of metastases were skeleton (43%), stomach (27%), lung (8%), and liver (4%). Diagnosis of gastric involvement was histologically confirmed in 41 patients and based on endoscopic features, despite negative biopsies in 10 patients. Six patients (12%) presented with nonfatal hemorrhage; in the others, symptoms were nonspecific: anorexia (71%), epigastric pain (53%), and vomiting (41%). Endoscopy showed 3 patterns: 18% localized lesions, 57% diffuse infiltration, and 25% external compression at the cardia or pylorus. Histology showed mainly lobular breast carcinoma (n = 36) compared with ductal carcinoma (n = 10) and other types (n = 5), contrary to the usual distribution. The overall response to systemic therapy was 46% (17 of 37 treated patients). Median survival from detection of gastric metastases was 10 months, with a 2-year survival rate of 23%. CONCLUSIONS: Gastric metastases usually derive from lobular rather than ductal breast carcinoma. Endoscopy revealed mainly a diffuse linitis plastica-like infiltration. Chemotherapy or hormonal treatment may result in fair palliation in selected patients, although many patients are heavily pretreated.

Adult↗

p27(kip1) expression in breast carcinomas: an immunohistochemical study on 512 patients with long-term follow-up.

p27(Kip1) (p27), a cyclin-dependent kinase inhibitor, has an important role in the progression of cells from G(1) into S phase of the cell cycle. p27 may act as a tumor suppressor, and several reports suggest that loss of its expression in breast carcinoma is related to tumor progression and poor prognosis. We evaluated p27 immunohistochemical expression in 512 consecutive cases of breast carcinoma with 9 years of median-term follow-up. p27 expression was heterogeneous and frequently less intense than in normal cells. Low p27 expression (<50% of reacting cells) was associated with grade III tumors, N0 status, estrogen receptor-negative status, and low cyclin D1 expression. In the whole series of cases, p27 expression did not predict outcome. In node-negative cases (249 patients), high p27 expression indicated poor prognosis. p27 was not prognostically relevant in the group of 223 patients with pT1 disease or in the group of 154 patients <50 years of age. We also investigated the prognostic value of the combined expression of p27 and cyclin D1, but no differences in survival were seen in this bivariate analysis.

Adult↗

Prognostic factors for survival after breast conserving therapy for stage I and II breast cancer. The role of local recurrence.

Risk factors for local recurrence (LR) in a univariate analysis had a significant correlation with survival. Local and distant failure could not be regarded as independent events. We undertook a multivariate survival analysis to study the relation between LR and survival. In a retrospective study of 1026 patients treated with tumorectomy, axillary dissection and radiotherapy, factors associated with disease-specific survival (DSS) were analysed. Actuarial estimates for DSS are 91% at 5 years and 86% at 10 years. The multivariate analysis revealed five factors: clinical stage, number of affected axillary nodes, histological grade, degree of tubule formation and left-sided primary tumour. Controlling for these factors, LR appeared to be significantly correlated with DSS. The hazard rate of DSS was estimated to increase by a factor 8.8 (95% confidence interval 4.6-16.8) upon occurrence of a LR. Local recurrence per se, apart from the identified prognostic factors, is a risk factor for DSS. The exact mechanism by which LR has an influence on survival cannot be clarified from these data.

Adult↗

Lymphedema-induced lymphangiosarcoma.

A series of eight patients with chronic lymphedema-related lymphangiosarcoma is presented. All but one case showed a typical rapid progression and fatal outcome, as has been reported in other series. In one patient the lymphangiosarcoma developed on the chest wall, the axilla and the arm where persisting lymphedema and fibrosis occurred after bilateral mastectomy and bilateral postoperative radiotherapy. In this patient an asymptomatic course and slow locoregional progression of lesions was seen. The clinical picture, the etiological considerations and the therapeutic options of the lymphedema-induced lymphangiosarcoma with regard to the literature are discussed.

Aged↗

Risk factors in breast-conservation therapy.

PURPOSE: To identify clinical and pathologic factors associated with an increased risk of local recurrence following breast-conservation therapy (BCT) to assess the safety of this procedure for all subgroups of patients. PATIENTS AND METHODS: The study population consisted of 1,026 patients with clinical stage I and II breast cancer treated between 1979 and 1988 at the Netherlands Cancer Institute. The BCT regimen consisted of local excision and axillary lymph node dissection (ALND) followed by whole-breast irradiation to a total dose of 50 Gy in 2-Gy fractions and boost irradiation (mostly by iridium implant) of 15 to 25 Gy. RESULTS: With a median follow-up duration of 66 months, the actuarial breast recurrence rate was 4% at 5 years, counting all breast recurrences. Univariate analysis showed seven factors to be associated with an increased risk of local recurrence; age, residual tumor at reexcision, histologic tumor type, presence of any carcinoma-in-situ component, vascular invasion, microscopic margin involvement, and whole-breast radiation dose. Three factors remained independently significant after proportional hazard regression analysis: age, margin involvement, and the presence of vascular invasion. When the analysis was repeated, but counting only those breast recurrences that occurred before regional or distant failures, only young age and vascular invasion were independent predictive factors. In the third analysis, factors predicting the necessity of local salvage treatment were analyzed. In this analysis, the possible bias in the former analysis caused by censoring actuarial methods was avoided. The results were the same as in the second analysis, showing young age and vascular invasion as the only independent predictive factors. Breast recurrence rates were 6% for patients less than 40 years of age and 8% for patients with tumors showing vascular invasion. In the absence of risk factors, the breast recurrence rate is only 1% at 5 years. CONCLUSION: Slightly higher recurrence rates were found in patients less than 40 years of age and in patients with tumors showing vascular invasion. The role of margin involvement is uncertain.

Actuarial Analysis↗

Further evaluation of the prognostic value of morphometric and flow cytometric parameters in breast-cancer patients with long follow-up.

The added prognostic value of cellular DNA content compared with single and combined morphometric factors and classical parameters such as tumor size, nodal status, histologic grade and estrogen receptor (ER) content was investigated in 225 consecutive breast-cancer patients with long follow-up. Of all features investigated, the MPI (multivariate prognostic index) had the strongest prognostic value [Mantel-Cox (MC) = 48.2, p less than 0.00005]. The results further showed that neither age nor ER content had significant prognostic value, but the DNA index (DI) as a single parameter had (though weak) prognostic significance (MC = 5.9, p = 0.015); a similar result was obtained with the percentage of S-phase cells (MC = 6.1, p = 0.013). The DI had (restricted) additional prognostic value to the morphometric features (MPI plus DI Mantel-Cox 53.0, p less than 0.0001). The percentage of S-phase cells had no additional prognostic value over the MPI. On the other hand, the additional value of the DI over tumor size and nodal status was much more impressive (MC = 41.0 and 40.7), although it did not reach the prognostic significance of the MPI. Prediction of disease outcome with a linear combination of quantitative microscopical parameters of the primary tumor alone [MAI (mitotic activity index), DI and mean nuclear area] was very accurate, even without considering lymph-node status (MC 30.8, p less than 0.0005). Grade had no additional value to the MPI at all (p = 0.76). This could be especially important for lymph-node-negative patients in whom the prognostic value of the MPI and the MAI are confirmed.

Breast↗

Limited prognostic value of cellular DNA content to classical and morphometrical parameters in invasive ductal breast cancer.

This retrospective study evaluates several prognostic factors in 63 patients with invasive ductal breast cancer. Special attention is paid to the additional prognostic value of cellular DNA content to the previously developed and evaluated quantitative features mitotic activity index (MAI) and multivariate morphometric prognostic index (MPI). Follow-up was monitored for at least 50 months (median survival, 78 months) and only patients who died of distant metastases were included. The results show that the MAI is the strongest prognostic factor of all single features (Mantel-Cox, P = 0.008). Although patients with a diploid or tetraploid tumor tended to have a better prognosis than those with an aneuploid cancer, the DNA index as a single parameter was a weak prognosticator in the univariate survival analysis (Mantel-Cox, P = 0.24). Within the diploid and tetraploid tumors the MAI could distinguish patients with a favorable and unfavorable prognosis prediction (chi-square, P = 0.01). For aneuploid tumors this was not possible. Analysis of combined features revealed that the MPI has a high prognostic value (Mantel-Cox, P = 0.0015), thus confirming other studies. A linear combination of the nuclear DNA index, MAI, nodal status, and mean nuclear area showed only a slight improvement in prognosis prediction compared with the MPI (Mantel-Cox, P = 0.0005); with this rule, the classification of the patients was more in agreement with the actual outcome in 4% of the cases. The gain was in the poor prognosis group. These results suggest that the additional prognostic value of nuclear DNA content is restricted when compared with the morphometric prognostic factors. Further studies on a larger number of patients are required to confirm these findings.

Breast Neoplasms↗

The spectrum of gastrointestinal metastases of breast carcinoma: I. Stomach.

In a 15-year period at the Netherlands Cancer Institute, 27 patients were found with breast carcinoma metastatic to the stomach. Presenting symptoms were non-specific, mainly nausea, vomiting, dysphagia, epigastric pain, and melena. Endoscopy, performed in 22 of these patients, yielded a correct diagnosis in 13. Lobular rather than ductal breast carcinoma was the predominant source of gastric metastases in this series. Non-surgical treatment was rewarded by a favorable, palliative response in 32% of cases.

Breast Neoplasms↗

The spectrum of gastrointestinal metastases of breast carcinoma: II. The colon and rectum.

In a 15-year period at the Netherlands Cancer Institute, 17 patients were found with breast carcinoma metastatic to the colon or rectum or both. The presenting symptoms and signs were non-specific and included diarrhea, crampy pain, vomiting, and palpable tumor. Endoscopic examination, possible in only 10 of the 17 patients because of luminal obstruction, yielded a correct diagnosis in seven cases. Biopsy was confirmatory in five cases. Lesions metastatic to the colorectum originated predominantly in lobular carcinoma of the breast. Systemic hormonal or chemotherapy or x-irradiation, either alone or as an adjunct to surgery, produced a favorable response in over half the patients so treated.

Breast Neoplasms↗