Study Of Invasive Breast Cancer Research Articles

Cyclin D1 and associated proteins in mammary ductal carcinoma in situ and atypical ductal hyperplasia.

Experimental studies suggest that cyclin D1 is a potential oncogene but in clinical studies of invasive breast cancer, overexpression of cyclin D1 is found to be associated with oestrogen receptor (ER) expression and low histological grade, both markers of good prognosis. Immunohistochemistry has been used to examine the relationship between cyclin D1 expression and differentiation in 36 cases of ductal carcinoma in situ (DCIS) and the interrelationship between expression of cyclin D1, its associated protein product of the retinoblastoma gene (pRb), and ER, in this group of cases. The expression of these markers has also been examined in nine cases of atypical ductal hyperplasia (ADH) and these results have been compared with the levels of expression seen in DCIS. Cyclin D1 overexpression was found in 23/36 (64 per cent) cases of DCIS and, in contrast to invasive carcinoma, there was no relationship with either differentiation or ER expression. The level of pRb expression was significantly associated with cyclin D1 expression (rS = 0.49, P = 0.001) and only two cases (6 per cent) were pRb-negative. There was no association between pRb and differentiation of DCIS or ER status. In contrast to DCIS, only one case of ADH showed overexpression of cyclin D1 (Mann-Whitney U-test, P = 0.02). All cases of ADH were ER-positive and showed moderate pRb staining, similar to that seen in well-differentiated DCIS. These results provide further evidence that overexpression of cyclin D1 plays a role early in carcinogenesis.

The need for epidemiologic studies of in-situ carcinoma of the breast.

The purpose of this paper is to present background information on carcinoma in situ (CIS) of the breast and to provide a theoretical framework for planning epidemiologic studies which may further our understanding of breast cancer. Two types of epidemiologic studies are needed which incorporate CIS of the breast: (i) case-control studies, in which in-situ lesions serve as disease outcomes (endpoints), and (ii) cohort studies and clinical trials, in which diagnosis of in-situ carcinoma serves as a starting point for patient treatment and follow-up. Case-control studies focusing on the causes of CIS have distinct advantages: if risk factors for cancer contribute to pathways involving some intermediate stages but not others (e.g. comedo-type but not non-comedo-type DCIS; LCIS versus DCIS), the use of precursor lesions may more clearly reveal risk factor associations than studies of invasive breast cancer alone; epidemiologic studies of precursor lesions are conducted closer in time to the exposures suspected to be causes and may reduce recall bias or other forms of misclassification; genetic alterations in early lesions are more likely to represent causal events in development of the malignant phenotype. Population-based case-control studies of CIS may thus prove useful in understanding breast cancer etiology and designing preventive strategies. CIS patients identified for case-control studies may be followed up over time as a cohort. Cohort studies (and clinical trials) of CIS aim to elucidate mechanisms influencing progression of CIS to invasive cancer as well as to evaluate effectiveness of specific treatment modalities. Although the majority of CIS lesions of the breast are ductal carcinoma in situ (DCIS), epidemiologic studies which also include patients with lobular carcinoma in situ (LCIS) address potential differences between DCIS and LCIS with respect to both etiology and progression.

Pathologic Findings from the National Surgical Adjuvant Breast Project (Protocol No. 4): II. The Significance of Regional Node Histology Other Than Sinus Histiocytosis in Invasive Mammary Cancer

The morphologic appearances of regional lymph nodes in radical mastectomy specimens obtained from 303 women entered into a prospective study of invasive breast cancer were categorized into patterns that have been considered to reflect immunologic function. An attempt was made to correlate these with 31 other histological and 8 clinical features, including short-term treatment failure (3 months to 4 years, average 24 months). No significant relationship to the latter was encountered. However, a lymphocyte predominance pattern was significantly associated with a stellate tumor border, absent cell reaction within the dominant tumor, absent sinus histocytosis of lymph nodes, combination tumor types, and a patient age of 55 years or more. A similar relationship between age of patient and sinus histiocytosis was found with the germinal center predominance pattern. In addition, this histologic appearance was associated with circumscribed tumors, severe cell reaction, and the infiltrating ductal carcinoma NOS and medullary types. Nodes with an unstimulated appearance were also found to be related to an absent cell reaction but marked sinus histiocytosis and a patient age of 45-54 years. Possible reasons for the differences between these findings and those of others relating prognostic value to such assessment of nodal histology is discussed, as are the findings of studies relevant to the identity of immunologic function with the morphologic appearance of nodal structure. The findings from this study fail to indicate any value of such nodal assessments as prognostic discriminants for breast cancer. Although longer periods of observation might alter this conclusion, such an event is regarded as unlikely.