Value of Memorial Sloan-Kettering Cancer Center nomogram in clinical decision making for sentinel lymph node-positive breast cancer.

BACKGROUND: The aim of this study was to determine the value of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram for individual decision making in a Dutch cohort of women with breast cancer with a positive sentinel lymph node (SLN) but at low risk of additional nodal metastases. METHODS: Data were collected on 168 patients with a positive SLN who underwent completion axillary lymph node dissection. The predicted probability of non-SLN metastases was calculated for each patient, using the MSKCC nomogram. Specificity and false-negative rates were calculated for subgroups with a predicted risk of no more than 5, 10 or 15 per cent. A receiver operating characteristic (ROC) curve was constructed and the area under the curve (AUC) calculated. RESULTS: The discrimination of the MSKCC nomogram, measured by the AUC, was 0.68. For low predicted probability cut-off values of no more than 5, 10 and 15 per cent, the false-negative rates were 20, 14 and 19 per cent, and the specificities were 4, 27 and 32 per cent, respectively. The low-risk category (5 per cent or less) consisted of only 3.0 per cent of the study population. CONCLUSION: The performance of the MSKCC nomogram was insufficient to make it a useful tool for individual decision making in this cohort of women with SLN-positive breast cancer.

[Acute abdominal pain and fever in a young woman as the first symptoms of lymphangioleiomyomatosis]. / Acute buikpijn en koorts bij een jonge vrouw als eerste verschijnselen van lymfangioleiomyomatose.

A previously healthy 28-year-old woman presented to the emergency clinic with acute severe abdominal pain and high fever. A diagnostic laparoscopy was performed, during which a large retroperitoneal tumour was found. A CT-scan of the abdomen and thorax confirmed the presence of a retroperitoneal mass but also revealed multiple renal angiomyolipomas and extensive cystic lesions in all lung fields. Based on these findings, the diagnosis lymphangioleiomyomatosis (LAM) was suspected, and later confirmed by histological examination of a biopsy specimen. The acute abdomen and fever appeared to have been caused by a Streptococcus agalactiae infection of the retroperitoneal lymphangiomyoma, which was treated with intravenous antibiotics. LAM is a very rare disease affecting mostly women of childbearing age and presenting almost exclusively with pulmonary symptoms. This is the first description of LAM presenting with an acute surgical abdomen and fever due to infection of a lymphangiomyoma.

Margin status and the risk of local recurrence after breast-conserving treatment of lobular breast cancer.

BACKGROUND: Invasive lobular breast carcinoma is known for its multicentricity and is associated with a higher incidence of incomplete excision after breast-conserving therapy. The aim of the study was to examine the influence of positive surgical margins on the local recurrence rate in patients diagnosed with invasive lobular cancer and treated with breast-conserving therapy. METHODS: All 416 women diagnosed with invasive lobular breast cancer and undergoing breast-conserving treatment between 1995 and 2002 were selected from the population-based Eindhoven Cancer Registry. Their medical charts were reviewed and detailed information was collected. RESULTS: The risk of margin involvement was 29% after the first operation and 17% when taking into account the final margin status of the patients undergoing re-excision. During follow-up, 18 patients developed a local recurrence. The 5 year actuarial risk of developing a local recurrence was 3.5% (95% confidence interval 2.5-4.5) and the 8 year risk was 6.4% (95% confidence interval 4.7-8.0). There was no influence of positive surgical margins on the risk of local recurrence, neither in the univariate analysis nor after adjustment for age, tumour size, nodal status and adjuvant systemic treatment. CONCLUSION: Patients with invasive lobular cancer, treated with breast-conservation, have a low risk of local recurrence, despite their high risk of having a microscopically incomplete excision of the tumour.

The significance of one positive axillary node.

AIMS: The aim of this study was to identify a subgroup of patients with breast cancer that can safely avoid axillary dissection. METHODS: Using data collected by the Eindhoven Cancer Registry, we compared the clinico-pathological features of 489 patients with only one positive lymph node to those of 817 patients with more than one positive lymph node in the axilla. All patients underwent complete axillary dissection, not preceded by a sentinel node biopsy. RESULTS: Tumour size greater than 1cm, harvesting more than 15 axillary lymph nodes at histopathological examination, metastasis size larger than 2mm, extranodal extension, and nodal involvement of the axillary apex are independently associated with the occurrence of more than one metastatic axillary lymph node. CONCLUSION: No subgroup could be identified in which axillary dissection can always be omitted. However, tumour size<1cm, finding a micrometastasis rather than a macrometastasis, and especially not finding extranodal extension were independently associated with finding only one positive axillary lymph node.

Long-term survival of T1 and T2 lymph node-negative breast cancer patients according to Mitotic Activity Index: a population-based study.

Node-negative breast cancer patients have a relatively good prognosis, but eventually one-third will die of the disease. Thus, prognostic factors to identify the high-risk group among these patients are needed. We retrospectively determined the Mitotic Activity Index (MAI) for a large series of node-negative breast cancer patients (n = 468) with tumours smaller than 5 cm, who only received locoregional treatment. Patients were followed for up to 29 years; crude and relative survival were calculated, both univariate and multivariate. Relative survival differed significantly according to MAI (p = 0.05), the difference occurred in the first 5 years after diagnosis and remained constant thereafter. After adjustment, MAI still significantly affected relative survival (RER, 1.9; 95% CI, 1.1-3.5). Tumour size also increased the risk, but this was not statistically significant (RER, 1.5; 95% CI, 0.8-2.7). Survival of patients with a T1 tumour and MAI < 10 was similar to that for the general population in the first 5 years after diagnosis. In conclusion, MAI significantly predicted long-term survival for T1/T2N0 breast cancer. Adjuvant systemic therapy appears to have little benefit for node-negative breast cancer patients with a T1 tumour, regardless of the MAI. For those with a T2 tumour and a MAI > or = 10 systemic therapy might have reduced mortality. The need for close surveillance of node-negative breast cancer patients with a T1 tumour and MAI < 10 seems limited.

The prognostic significance of axillary lymph-node micrometastases in breast cancer patients.

AIMS: We analysed the results of regional community practice to determine the prognosis of axillary lymph-node micrometastases in women with breast cancer. METHODS: Patient data were retrieved from the population-based Eindhoven Cancer Registry in The Netherlands. Between 1975 and 1997, 10,111 patients were diagnosed as having invasive breast cancer. We compared three subgroups: patients without axillary involvement (the pN0 group), patients with axillary micrometastasis (< or = 2 mm, the pN1a group), and patients with a macro metastasis in only one lymph node (> 2 mm, the pN1 group). Follow-up was completed until April 2002. RESULTS: The relative risk (RR) of dying comparing the pN1a group and the pN1 group to the pN0 group was 1.32 and 1.34, respectively. Excluding the adjuvantly treated patients, the RR of dying was 1.51 and 1.91, respectively for the pN1a group and the pN1 group vs. the pN0 group. CONCLUSION: This outcome data of nearly 25 years of community practice show that breast cancer patients with axillary lymph node micrometastasis have a significantly worse survival rate than those without independent of age or tumour size. Adjuvant systemic therapy should be contemplated when treating these patients.

Trends in breast cancer aggressiveness before the introduction of mass screening in southeastern Netherlands 1975-1989.

OBJECTIVE: The increased incidence of breast cancer in the southeastern Netherlands was accompanied by markedly improved relative survival and stable mortality. We investigated whether the average aggressiveness of tumors changed over time in a population-based study, before the introduction of mass screening. METHODS: The mitotic activity index (MAI) was determined retrospectively for 1051 consecutive patients diagnosed with invasive, non-metastatic breast cancer in 1975, 1981, 1988, and 1989. Trends over time, and effects of age, tumor size and lymph node status were examined by univariate and multivariate regressions. RESULTS: Age-adjusted incidence of low MAI tumors changed from 35/100,000 in 1975 to 45/100,000 in 1988-89, an increase of 30% (P = 0.01), the incidence of tumors with a high MAI increased about 20% (P = 0.28), from 25 to 29/100,000. For small tumors (T1) the odds for a high MAI was lower in 1981 (OR: 0.80; 95% CI: 0.37-1.73) and 1988-89 (OR: 0.66; 95% CI: 0.35-1.23) compared to 1975. Among T3 and T4 tumors the odds increased to 2.03 (95% Cl: 0.71-5.86) in 1981 and 2.16 (0.76-6.18) in 1988-89. CONCLUSION: Although the incidence of tumors with low aggressive potential increased, the incidence of high MAI tumors also increased. Stable breast cancer mortality rates in the face of increasing incidence rates during the period 1975-89 cannot be attributed solely to changes in tumor aggressiveness; early diagnosis and better treatment may also have contributed.

Treatment of 100 patients with sentinel node-negative breast cancer without further axillary dissection.

BACKGROUND: The sentinel node biopsy technique for breast cancer has been validated extensively in phase I and II studies. However, no data from phase III randomized clinical studies are available. It remains controversial whether a histologically negative sentinel node biopsy without further axillary dissection can be considered to be good clinical practice. METHODS: One hundred consecutive patients with breast cancer who had a negative sentinel node biopsy without additional axillary dissection were studied prospectively between 1997 and 2000 in order to identify tumour recurrence and to assess the morbidity of the sentinel node procedure. Special attention was paid to axillary or locoregional recurrence, distant metastases and overall survival. One year after the procedure patients were sent a questionnaire to assess any functional impairment of the arm or shoulder. RESULTS: Median follow-up was 24 (range 16-40) months. One patient had an axillary relapse 14 months after the initial diagnosis of breast cancer. She died after 2 years from metastatic disease. There were no other local axillary recurrences. There was a 94 per cent response rate to the questionnaire. Twelve patients developed mild disabilities, of whom two said that they had to change their hobbies, sports or daily activities owing to the sentinel node procedure. No patient developed lymphoedema or needed physiotherapy after the operation. CONCLUSION: When strict criteria for the sentinel node biopsy procedure are used, the sentinel node biopsy without further axillary dissection after a negative histological investigation is a safe procedure. It may therefore be considered to be the standard of care for the treatment of patients with breast cancer.

The risk of nodal metastases in breast cancer patients with clinically negative lymph nodes: a population-based analysis.

A population-based study was performed to assess the likelihood of axillary lymph node metastases in patients with clinically negative lymph nodes, according to patient age, tumor size and site, estrogen receptor status, histologic type and mode of detection. Data were obtained from the population-based Eindhoven Cancer Registry. During the period 1984-1997, 7680 patients with invasive breast cancer were documented, 6663 of whom underwent axillary dissection. Of the 5125 patients who were known to have clinically negative lymph nodes and underwent axillary dissection, 1748 (34%) had positive lymph nodes at pathological examination. After multivariate analysis, histologic type, tumor size, tumor site and the number of lymph nodes in the axillary specimen remained as independent predictors of the risk of nodal involvement (P < 0.001). Lower risks were found for patients with medullary or tubular carcinoma, smaller tumors, a tumor in the medial part of the breast and patients with less than 16 nodes examined. This study gives reliable estimates of the risk of finding positive lymph nodes in patients with a clinically negative axilla. Such information is useful when considering the need for axillary dissection and to predict the risk of a false-negative result when performing sentinel lymph node biopsy.

The relationship between findings on pre-treatment mammograms and local recurrence after breast-conserving therapy for invasive breast cancer.

AIMS: This study was planned (a) to determine the correlation between findings on the pre-treatment mammogram and local recurrence after breast-conserving therapy (BCT), and (b) to analyse the relationship between mammographical features, specific pathological characteristics and the need for re-excision. METHOD: The size and outline of the lesion, the presence of suspect microcalcifications and signs of multifocality on pre-treatment mammograms of 39 patients with local recurrence after BCT and 126 randomly selected control patients without local recurrence were compared. Tissue slides of the primary tumour were reviewed to confirm the histological type and grade, the aspect of the margins, microscopic margin involvement, presence of vascular invasion and the presence and extent of an intraductal component. RESULTS: Among patients /=50 years, 67% of the patients with local recurrence had a non-circumscribed lesion compared to 9% of the control group (P<0.001). Suspect microcalcifications on the mammogram were associated with the finding of an extensive intraductal component, vascular invasion and a higher histological grade by the pathologist. Patients with a non-circumscribed density or a scirrhous lesion needed re-excision more often (30 and 33%, respectively) than those with a well-circumscribed density (9%). CONCLUSIONS: Although the number of patients was small, this study indicates that some mammographical features are associated with a higher risk of local recurrence after BCT and the need for re-excision. This was supported by the findings of the pathological review.

Prognostic value of DNA ploidy using flow cytometry in 1301 breast cancer patients: results of the prospective Multicenter Morphometric Mammary Carcinoma Project.

The literature on breast cancer reports conflicting prognostic results with respect to DNA ploidy of flow cytometric DNA histograms. This might result from different DNA ploidy classification methods. Our study evaluated the prognostic power of DNA ploidy, using different classification methods, in a large prospective group (n = 1301) of breast cancer patients. Flow cytometric DNA histograms obtained from fresh frozen material were interpreted with use of a commercially available computer program. On the basis of the number of stemlines and the DNA Index, we classified the DNA ploidy by different methods. In all of the cases, the classification method "DNA diploid versus DNA nondiploid" provided the best prognostic significance for overall survival (OS) (Mantel-Cox (MC) = 5.4, P = .02; relative risk (RR) = 1.3, P = .05) and for disease-free survival (DFS) (MC = 11.8, P = .0006; RR = 1.3, P < .05). This was also true for the OS of the lymph node-positive (but not the lymph node-negative) subgroup (MC = 4.1, P = .04; RR = 1.3, P = .05). In subgroups classified on the basis of tumor size, DNA ploidy showed prognostic significance for DFS only in the subgroup of tumors smaller than 2 cm and larger than 5 cm. In multivariate analysis, DNA ploidy showed no additional prognostic power to lymph node status and tumor size. The classification "DNA diploid versus DNA nondiploid" was mostly consistent with respect to prognostic power for OS and DFS, especially in small or lymph node-positive tumors. The RR of DNA nondiploid patients was only marginally higher, however, so large study groups are required to reach statistical significance. This could partly explain the disagreements in the literature. Therefore, DNA ploidy seems to be of little clinical importance in breast cancer patients, compared with other prognostic parameters.

Prognostic implications of different cell cycle analysis models of flow cytometric DNA histograms of 1,301 breast cancer patients: results from the Multicenter Morphometric Mammary Carcinoma Project (MMMCP).

Conflicting prognostic results with regard to DNA flow cytometric cell cycle variables have been reported for breast cancer patients. An important reason for this may be related to differences in the interpretation of DNA histograms. Several computer programs based on different cell cycle fitting models are available resulting in significant variations in percent S-phase and other cell cycle variables. Our present study evaluated the prognostic value of percent S-phase cells obtained using 5 different cell cycle analysis models. Flow cytometric DNA histograms obtained from 1,301 fresh frozen breast cancer samples were interpreted with 5 different cell cycle analysis models using a commercially available computer program. Model 1 used the zero order S-phase calculation and "sliced nuclei" debris correction, model 2 added fixed G2/M- to G0/G1-phase ratio, and model 3 added correction for aggregates. Model 4 applied the first-order S-phase calculation and sliced debris correction. Model 5 fixed the coefficients of variation CVs of the G0/G1- and G2/M-phases in addition to applying the sliced nuclei debris correction and zero order S-phase calculation. The different models yielded clearly different prognostic results. The average percent S-phase cells of the aggregate correction model (model 3) provided the best prognostic value in all cases for overall survival (OS) as well as disease-free survival (DFS) (OS: p < 0.0001; DFS: p < 0.0001), in lymph node-positive cases (OS: p < 0.0001; DFS: p = 0.004) and in DNA-diploid subgroups (OS: p = 0.004; DFS: p = 0.001). For the lymph node negative and DNA-non-diploid subgroups, the percent S-phase of the second cell cycle reached slightly better prognostic significance than the average percent S-phase cells. In multivariate analysis, the average percent S-phase of the aggregate correction model had the best additional prognostic value to tumor size and lymph node status. In conclusion, different cell cycle analysis models yield clearly different prognostic results for invasive breast cancer patients. The most important prognostic percent S-phase variable was the average percent S-phase cells when aggregate correction was included in cell cycle analysis.

Changing attitudes towards breast-conserving treatment of early breast cancer in the south-eastern Netherlands: results of a survey among surgeons and a registry-based analysis of patterns of care.

To see whether personal preferences of surgeons can explain the trends in the use of breast-conserving therapy (BCT) of early breast cancer, questionnaires were sent to the surgeons of seven community hospitals in the south-eastern Netherlands in 1987 and 1995. The answers were set against the actual use of breast-conserving therapy in the hospitals in the period 1984-94, as monitored by the Eindhoven Cancer Registry. The proportion of surgeons who were willing to use BCT for tumours < or =3 cm increased from 43% in 1987 to 93% in 1995. In 1995, the majority of the surgeons considered multicentric tumour growth, diffuse microcalcifications on the mammogram and an extensive intraductal component around the tumour as contraindications for breast-conserving therapy. The proportion of patients with an operable, non-metastasized breast tumour of < or =5 cm in diameter undergoing breast-conservative surgery increased from 31% in 1984 to 60% in 1989 (P<0.01) and remained at that level in 1990 and 1991. Between 1991 and 1993, the proportion receiving breast-conservative surgery decreased significantly for patients younger than 50 years and a tumour 2.1-3.0cm in diameter, and also for those 50-69 years old with a tumour < or =2.0cm or 3.1-5.0cm across. The observed decrease in BCT in the south-eastern Netherlands in some subgroups seems to reflect the growing awareness of potential risk factors for local recurrence following BCT.

Management of early breast cancer in southeast Netherlands since 1984. A population-based study. Regional Breast Cancer Study Group.

We studied changes in staging and treatment of patients with early breast cancer (TNM stage I and II) in eight community hospitals in southeast Netherlands between 1984 and 1991 and related these changes to the guidelines for the management of breast cancer drawn up by the regional Breast Cancer Study Group. Since 1984, the proportion of patients that underwent breast-conserving therapy (local tumour excision, axillary dissection, and irradiation of the breast) increased from 26% to 53%. Although the mean number of axillary lymph nodes examined by the pathologists increased significantly, the proportion of patients with positive lymph nodes remained unchanged. The proportion of patients with involved axillary nodes receiving any form of adjuvant systemic therapy increased from 49% to 82%. Therapeutic policy initially varied significantly from one hospital to another but gradually became more uniform. We conclude that, except for elderly patients, treatment of early breast cancer corresponded increasingly to the guidelines of the regional Breast Cancer Study Group.

[Increased incidence of breast cancer in southeast Netherlands between 1960 and 1989]. / Toegenomen incidentie van borstkanker in Zuidoost-Nederland tussen 1960 en 1989.

Trends in incidence, stage distribution and mortality of breast cancer were determined in the Southeastern Netherlands in 1960-1989. First and second primary breast cancers were analyzed separately. The incidence and mortality rates were age-standardised according to the European Standard Population. The incidence rate of first primary invasive breast cancer increased from 50 per 100,000 women per year in 1960-61 to 96 in 1988-89, and of second primary invasive breast cancer from 3.2 in 1965-66 to 7.8 in 1988-89. The incidence rate of first primary ductal carcinoma in situ (DCIS) increased from 0.3 per 100,000 women per year in 1975-76 to 2.8 in 1988-89 and of second primary DCIS from 0.06 in 1975-79 to 0.4 per 100,000 in 1985-89. The increase in first invasive primaries was observed in all age groups, but mostly at age 75 and over. The percentage with stage I tumours of the patients with a first primary invasive breast cancer increased from 7% in the sixties to 27% in the eighties, whereas the percentage of stage III and IV tumours combined, decreased from 39% in the sixties to 26% in the eighties. While age-adjusted incidence of first primaries almost doubled in the past thirty years, breast cancer mortality rose only slightly. However, breast cancer mortality showed a proportionate increase of total mortality from 4.5% in 1970-71 to 6.3% in 1988-89.(ABSTRACT TRUNCATED AT 250 WORDS)

The Multicenter Morphometric Mammary Carcinoma Project (MMMCP). A nationwide prospective study on reproducibility and prognostic power of routine quantitative assessments in The Netherlands.

The Multicenter Morphometric Mammary Carcinoma Project (MMMCP) has been set up to investigate prospectively the prognostic value and reproducibility of routine assessments of the morphometric Multivariate Prognostic Index (MPI) and other quantitative parameters in comparison with classical prognosticators and steroid receptors in breast cancer patients. In this project, 34 hospitals participate, divided over six geographically different regions. Of each patient entering in the study, multiple clinical and classical pathological parameters (including tumor size and lymph node status) as well as several quantitative parameters such as mean nuclear area, DNA index and mitotic activity index will be evaluated. Of all patients, the MPI will be assessed with tumour size, lymph node status and mitotic activity index. The quantitative assessments are performed in all consecutive breast cancers which enter the participating pathology laboratories, and all measurements are controlled in Amsterdam. The patient intake time will be from January 1, 1988 until January 1, 1990. It is expected that 3000 patients will enter in this study. Follow up data will be gathered up to 10 years. However, two to five years after the initiation of the Project, a first evaluation of the reproducibility and prognostic significance of routine MPI and other assessments in breast cancer patients will be possible. A detailed description of this project is given.

Polyneuropathy due to polyangiitis overlap syndrome.

A patient presented with a mild polyneuropathy, developed a large intra-abdominal haemorrhage and died of cardiac arrest within a few days. Microscopic examination revealed a polyangiitis overlap syndrome (Fauci) with lesions in many organs, including the peripheral nerves and the heart. A myocarditis was considered to be the cause of death.

Mesenteric cysts.

7 new cases of cysts in the mesentery of the small bowel are presented, together with 54 clinically and histologically well documented cases from the literature. Most cysts are found in laparotomy for an acute abdomen. Almost half of the patients are under the age of 11 years. The cysts can be unilocular, multilocular or multiple. Cysts in the mesentery of the jejunum always had a chylous content. Most often the wall consists of an endothelial lining, smooth muscle, lymphatic tissue and lymphatic vessels. Inflammation and/or bleeding destroyed the endothelial lining and added granulation tissue to the histologic picture. With the exception of 7 cases, the cysts are probably of congenital and lymphatic origin. Trauma, infection, bleeding or volvulus can make a silent cyst manifest.