Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

Background: Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF).

Methods: A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women).

Correlation of growth fraction by Ki-67 and proliferating cell nuclear antigen (PCNA) immunohistochemistry with histopathological parameters and prognosis in primary breast carcinomas.

The immunoreactivity for Ki-67 and PCNA was investigated in 487 patients with primary breast carcinomas using MIB-1 (Immunotech, France) and PC-10 (DAKO, Denmark) as primary antibodies. Formalin-fixed and paraffin-embedded tissue sections were used. The immunoreactivity for Ki-67 and PCNA was found to be independent of the length of fixation if the sections were pretreated in a microwave oven in citrate buffer and distilled water, respectively.

Medullary carcinoma of the breast. Prevalence and prognostic importance of classical risk factors in breast cancer.

In an earlier study of 235 breast cancers with medullary features, we concluded from a multivariate Cox regression analysis that only four histopathological features contained significantly positive prognostic information. In the present study, continuing our work on the same population base, we used these histological characteristics (predominantly syncytial growth pattern, no tubular component, diffuse stromal infiltration with mononuclear cells and sparse necrosis (< 25%), as diagnostic criteria for medullary carcinoma of the breast (MC). We found a significantly better prognosis for patients with MC than those with non-medullary carcinoma (NMC) or infiltrating ductal carcinoma (IDC).

[Significance for prognosis of delayed diagnosis and treatment of breast cancer].

In a study of 7608 patients with primary breast cancer the effect of patient's and doctor's delay on survival was examined. The delay was arbitrarily divided into the following intervals: Short (0-14 days), intermediate (15-60 days) and long (> 60 days). The delay had significant influence on survival.

The prognostic significance of immunohistochemically detectable metallothionein in primary breast carcinomas.

Metallothionein (MT) is a low-molecular-weight protein with a high affinity for group II metal ions, especially zinc and copper. MT serves as an intracellular reservoir of these ions, but may also be involved in the detoxification of certain toxic metal ions such as cadmium. In addition, high MT contents might protect tumour cells from alkylating agents and irradiation.

Proliferating cell nuclear antigen (pcna) and C-erbb-2 oncoprotein in breast-carcinoma with correlations to histopathological parameters and prognosis.

Overexpression of PCNA (more than 25% positive tumour cells) and positivity of c-erbB-2 oncoprotein were immunohistochemically demonstrated in 490 formalin-fixed and paraffin-embedded breast carcinomas. Overexpression of PCNA and c-erbB-2 correlated with large tumour size, presence of lymph node metastases, high histological grade (poor differentiation), and absence of steriod hormone receptors features indicating an aggressive phenotype. In univariate analysis overexpression of PCNA correlated with poor overall survival (p<0.

Immunohistochemical detection of metallothionein in primary breast carcinomas and their axillary lymph node metastases.

Metallothioneins (MTs) are low-molecular-weight proteins with specific binding for group II metal ions. MTs are involved in the detoxification of metals, but can also play a role in protection of the cell against certain anticancer agents and from damage of irradiation. High expression of MTs in primary breast carcinomas has been found to be associated with poorer prognosis.

The prognostic-significance of cathepsin-d in breast carcinomas - an immunohistochemical study.

Cathepsin D, a lysosomal protease, was examined by immunohistochemistry in 481 breast carcinomas. The immunoreactivity for cathepsin D was registered in the tumour cells, in the surrounding stroma, and in the macrophages and correlated with clinicopathological parameters. In univariate analysis of survival data, less than 25% positive tumour cells, any positivity in the stroma, and moderate or strong positivity in the macrophages were poor prognostic parameters.

[Breast cancer in the county of Viborg during 1983-1989. A quality control study].

The aim of the present study was to compare the quality of treatment for breast cancer in Viborg County to that provided in the rest of Denmark during the period 1983 to 1989. Women younger than 70 years of age with the diagnosis of invasive breast carcinoma and registered in the DBCG (Danish Breast Cancer Cooperative Group) were included, 435 from Viborg county and 11,434 from the rest of Denmark. No differences were found between the two patient-groups with regard to tumoursize, degree of anaplasia, number of axillary lymph nodes removed or number of positive lymph nodes.

[The significance of prognostic factors on the occurrence of metastases from breast cancer to various localizations].

The aim of the study was to identify and compare risk factors for development of metastases from breast cancer at specific anatomical sites. The sites were grouped into ten categories, simultaneous occurrences at several sites being common. The influence of various risk factors for recurrence at one specific site can be modelled by well-established survival analysis techniques such as the Cox regression model.

Patient's and doctor's delay in primary breast cancer. Prognostic implications.

In a study of 7,608 patients with primary breast cancer patient's and doctor's delay were examined in relation to age, tumour size, grade of anaplasia, and number of positive lymph nodes. The delays were arbitrarily divided into the following intervals: Short (0-14 days), intermediate (15-60 days) and long (> 60 days). The well-established patient and tumour characteristics were shown to have prognostic significance.

Medullary carcinoma of the breast, prognostic importance of characteristic histopathological features evaluated in a multivariate Cox analysis.

In this study of 136 breast cancers with medullary features (MC), registered in the Danish Breast Cancer Cooperative Group (DBCG) from 1982 to 1987, we confirmed the prognostic importance of a new definition of medullary carcinoma of the breast (MC newdef) which was recently proposed by us, deduced from a previous study of a corresponding tumour material (DBCG 77-82). However, the individual histological criteria did not have the same prognostic importance as in our previous study, although prognostic trends were the same. To further improve and validate the diagnostic criteria, we combined the two populations and performed a multivariate Cox regression analysis.

The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG).

In primary, operable breast cancer, the Nottingham Prognostic Index (NPI) based on tumour size, lymph node stage and histological grade can identify three prognostic groups (PGs) with 10-year survival rates of 83%, 52%, and 13%. With the aim of defining a subset of patients having so good prognosis that adjuvant therapy can be withhold, the NPI was applied to a Danish population-based study group comprising 9,149 patients. As opposed to the British study, we used conventional axillary lymph-node staging.

Vimentin expression in 98 breast cancers with medullary features and its prognostic significance.

The expression of vimentin, as assessed by immunohistochemistry, has been evaluated in 69 medullary carcinomas of the breast: 28 typical medullary carcinomas (TMC), 41 atypical medullary carcinomas (AMC), and 29 invasive ductal carcinomas with subtle medullary features that, however, did not fulfill the strict criteria of TMC or AMC. Immunoreactivity of at least 10% of the component cells was found in 14 of the medullary carcinomas (5 out of 28 TMC, 9 out of 41 AMC whereas only 1 of the invasive ductal carcinomas was vimentin-positive. The patients were followed for 8-13 years.

Lobular carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group.

In a Danish nationwide prospective study of in situ carcinomas and atypical lesions of the breast, 88 women, comprising 69 patients with lobular carcinoma in situ (LCIS) and 19 patients with combined lobular and ductal carcinoma in situ (LCIS + DCIS), were accrued from 1982 through 1987. All cases were treated with excision only. Within a median follow-up time of 61 months, a recurrence rate of 17% (15 cases) was found, excluding nine cases of refinding of LCIS.

Ductal carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group.

In a Danish nationwide prospective study of in situ carcinoma of the breast, 112 women with ductal carcinoma in situ, treated with excision only, were registered from 1982 to 1987. Within a median follow-up of 53 months, a crude recurrence rate of 22% (25 cases) was found, of which five cases recurred as invasive carcinomas and 20 cases as in situ carcinomas. The histopathologic review included a single-parameter analysis of histological growth pattern, size of lesion, nuclear size, presence of comedonecrosis, and subhistologic type.

[Axillary dissection in primary surgical treatment of breast cancer: risk of false-negative axillary status].

The present study evaluates the extent of axillary dissection as part of the primary surgical treatment of operable breast cancer. Data are from the period January 1979 to August 1990 and were collected prospectively as part of the Danish Breast Cancer Cooperative Group protocols for low-risk mammary carcinoma. The series consists of 6774 breast cancer patients aged 69 years or younger.

Differential influence of prognostic factors on the occurrence of metastases at various anatomical sites in human breast cancer.

The present study was initiated by data on the anatomical occurrence of metastases from breast cancer. Metastases may occur at various organs, here grouped into ten categories, and simultaneous occurrences at several sites are common. Our aim was to identify and compare risk factors for development of metastases at each site.

Axillary dissection of level I and II lymph nodes is important in breast cancer classification. The Danish Breast Cancer Cooperative Group (DBCG).

In order to define the term "a node-negative patient", the axillary nodal status at the primary operation for breast cancer was evaluated in 13,851 patients registered by the Danish Breast Cancer Cooperative Group (DBCG). The determinants for node negativity in primary breast cancer were the number of lymph nodes removed and the tumour size. The number of lymph nodes removed should be at least 10 to exclude misclassification of node-positive patients as node negative.

Survival of breast cancer patients in relation to factors which affect the risk of developing breast cancer.

In order to evaluate the prognostic significance of risk factors for developing breast cancer, a population-based study was conducted of 2,445 breast cancer patients diagnosed in Denmark, 1983-1984. Data on clinical and pathological characteristics of breast cancer were derived from the Danish Breast Cancer Cooperative Group and data on risk factors from a self-administered questionnaire. Among 1,744 patients (71%) with complete information, survival was determined primarily by size of the tumour, skin invasion, number of positive lymph nodes and grade.

Medullary carcinoma of the breast, proposal for a new simplified histopathological definition. Based on prognostic observations and observations on inter- and intraobserver variability of 11 histopathological characteristics in 131 breast carcinomas with medullary features.

In a previous study of 131 breast carcinomas with medullary features, we evaluated the diagnostic inter- and intraobserver variation and its prognostic implications using the criteria of typical (TMC) and atypical (AMC) medullary carcinoma of the breast put forward by Ridolfi et al. (1977). We found a considerable interobserver variation as well as intraobserver variation, with significant implication on prognosis, and concluded that the histopathological definition of MC must be sharpened and simplified in order to increase the diagnostic reproducibility.

Pattern of spread and progression in relation to the characteristics of the primary tumour in human breast cancer.

Characteristics of primary breast tumours were related to the extent of dissemination, the anatomical location of metastases, and the rate of progression in 863 patients with recurrent breast cancer. The following features were examined: tumour laterality, location within the breast, size, invasion of skin or fascia, presence of residual cancer tissue (RCT) in the mastectomy specimen, and number of positive lymph nodes. Increasing tumour size, increasing number of nodes, and the presence of local invasion and RCT were all associated with a short duration of survival both from initial diagnosis and from first recurrence.

The prognostic importance of syncytial growth pattern in medullary carcinoma of the breast.

The histopathological criteria for medullary carcinoma of the breast (MC) used by most pathologists today were delineated by Ridolfi et al. in 1977. The prime criterion is: "A predominantly syncytial growth pattern", predominantly being defined as including 75% or more of the tumour.

The limited value of routine chest X-ray in the follow-up of stage II breast cancer.

In 280 patients with stage II breast cancer, chest X-ray was performed at 6 and 12 months and yearly thereafter to the 6th year or until recurrence, another cancer was detected, the patient refused further follow-up or died. Among 1289 scheduled chest X-rays, malignant changes were found in 20 patients, of which only 3 had pulmonary symptoms. In a further 14 patients malignant changes were suspected, but follow-up examinations could not prove malignancy.