ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00240.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

From 1977 to 1986, 264 women with stage I or II breast cancer and positive breast cancer family histories were treated with conservative surgery, axillary dissection, and irradiation. The records of these cases were reviewed and compared to those of 517 women with stage I or II breast cancer and negative breast cancer family histories who were treated similarly during the same time period. Patients with a negative family history were more likely to present with positive axillary lymph nodes than patients whose history was positive (33% vs. 26.5%, p = 0.054). There were no statistically significant differences found between the family history positive and family history negative women in terms of 5 and 10 year actuarial overall survival (5 yr: 91% vs. 90%, 10 yr: 86% vs. 82%) or relapse‐free survival (5 yr: 76% vs. 76%, 10 yr: 64% vs. 61 %). Breast recurrence rates were likewise not significantly different for the two groups of patients (5 yr: 6% vs. 9%, 10 yr: 17% vs. 18%). A separate analysis restricted to lymph node‐positive patients revealed no significant differences in survival between the family history positive and family history negative groups. It thus appears that women with early stage breast cancer who have a family history of the disease can be treated with breast‐conserving surgery and definitive irradiation with the same excellent results as seen in women without such a family hi

ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00241.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Fine‐needle aspiration biopsy has proven to be an accurate and well‐tolerated procedure with a reported specificity of 99% and sensitivity of 70–99%. Similarly, nonpalpable breast lesions can be effectively sampled by needle biopsies under radiologic guidance. Breast aspirates have also been extensively utilized for assessment of nuclear grade, hormone receptor status, ploidy status, and proliferation rate, and have proven to be an attractive alternative to surgical biopsy. Using strict cytologic criteria, it may also be possible to recognize the cytomorphologic changes in breast lesions that are associated with increased risk for subsequent development of breast cancer. Presence of myoepithelial cells within the clusters of atypical epithelial cells recognized morphologically and/or detected by immunostaining for muscle specific actin is an important diagnostic feature of proliferative breast disease with atypia (atypical hyperplasia). This recognition has significant clinical implications and is important in the design of chemoprevention trials. The cytologic distinction between carcinoma in situ and invasive breast cancer remains diff

ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00242.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00243.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Surrogate endpoint biomarkers (SEBs) are tissue changes observed in premalignant disease that highly correlate with cancer risk. They are urgently needed as endpoints in clinical trials of chemopreventive agents for breast premalignant disease because they require less time, money and effort compared to the conventional endpoint of cancer incidence reduction. The program of the Chemoprevention Branch, NCI, is supporting 30 clinical trials of various chemopreventive agents for premalignant disease in different organ systems that are being monitored by the SEBs of DNA aneuploidy, abnormally high proliferative index, abnormal nuclear morphometry (aberrant size, shape, texture, and pleomorphism) and nucleolar number, position in the nucleus, and morphometry. Evidence from the literature permits the expectation that in premalignant breast disease these SEBs, when measured by computer‐assisted quantitative image analysis, will accurately predict the risk of recurrence of breast DCIS after lumpectom

ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00244.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Several groups of investigators have explored the possibility that widespread morphologic and molecular changes in breast tissue of high‐risk women may exist prior to breast cancer development and that these changes might be detected by random sampling. These tissue changes might serve as risk bio‐markers if they are found to be associated with the development of cancer in prospective trials.We review here studies of morphologic and molecular abnormalities in nipple and fine needle aspirates in women at high risk for breast cancer. Cytologic evidence of hyperplasia with atypia detected by random sampling appears to have particular potential for development as a risk biomarker. If this morphologic change is found to be reversible with chemopreventive agents that are later found to prevent or delay the appearance of cancer, then hyperplasia with atypia as detected by random sampling may serve as a surrogate endpoint biomarker for response in phase II chemoprevention tri

ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00245.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Biomarkers are increasingly important in the analysis of a wide variety of neoplastic processes including breast cancer. While p53, p185erbB‐2, and epidermal growth factor (EGF) receptor are considered to be well‐characterized biomarkers in ductal carcinoma in situ (DCIS) and in invasive adenocarcinoma of the breast, the characterization of these biomarkers by immunohistochemistry may be problematic. ErbB‐2 protein (p185erbB‐2) must be identified clearly on cytoplasmic membranes for breast cancers to be classified as overexpressing p185erbB‐2while ignoring cytoplasmic expression. For p53, nuclear staining and the percent of positive cells are considered, but rules for “cut‐offs” of numbers of positive cells for a case to be classified as positive are not defined. Problems with immunodetection of biomarkers using immunohistochemical techniques can be subdivided to problems with the antigen, the antibody, fixation‐tissue processing, and evaluation‐interpretation. For example, the initial methods of fixation and tissue processing can modify both the pattern and intensity of immunohistochemical identification of specific antigens and localization of receptors may change after the receptor‐ligand interactions. We have evaluated the effects of fixation both on the immunolocalization and intensity of expression of p53, p185erbB‐2and EGF receptor. We also have studied the patterns of p185erbB‐2, p53, and EGF‐receptor expression in a series of breast cancers evaluated concomitantly with a group of prostate cancers. Our results confirm that p53 mutations are common in breast cancer and that there is strong expression of p185erbB‐2on the membranes of a subset of breast cancers. The patterns of staining for both p53, p185erbB‐2, and EGF‐receptor are different in prostate and breast cancers. For example, higher concentrations of primary antibody to p53 protein and to p185erbB‐2are necessary to demonstrate nuclear p53 accumulation or membrane p185erbB‐2expression in prostate cancers than in breast cancers. In contrast, a higher concentration of antibody to the EGF‐receptor is necessary to demonstrate EGF‐receptor expression in breast cancers than in prostatic adenocarcinoma. Neutral buffered formalin is a poor initial fixative compared with other fixatives for demonstrating p53 accumulation or p185erbB‐2expression. The effect of formalin fixation can be reversed with antigen retrieval methods increasing detection markedly in cells with nuclear p53 accumulation. Antigen retrieval techniques were not effective in increasing immunodetection of p185erbB

ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00246.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Estrogen and progesterone are necessary for lobulo‐alveolar development of the human breast, and there is an abundance of epidemiologic literature implicating estrogen and possibly progesterone exposure as promoters of breast malignancy. The investigation of estrogen receptor (ER) and progesterone receptor (PgR) distribution in normal and benign breast tissue may be a measure of susceptibility of the tissue to these hormones. Earlier data from radioligand binding assays showed that benign breast tissue expressed little or no ER; newer immunohistochemical (IHC) methods have led to the investigation of benign breast tissue from at least 1243 women in 12 studies in the last 9 years. These show that the level of expression of ER and PgR in normal breast epithelium is significantly lower than in receptor positive carcinomas. Immunostaining patterns for both receptors show a great deal of heterogeneity. There is general agreement that stromal and myoepithelial cells are negative for both ER and PgR. A growing body of evidence suggests that PgR is the dominant sex steroid receptor in the normal breast. Mean values for PgR positive cells in breast epithelium range from 24% to 29%; ER is positive by IHC in 3% to 15.6% of normal breast epithelial cells. No firm conclusions are possible as yet regarding overexpression in proliferative epithelium. There is agreement that the proportion of ER positive cells declines in the second half of the menstrual cycle, but there is no clear cut relationship between PgR positivity with the menstrual cycle. Oral contraceptive use appears to decrease the proportion of ER positive cells, and increase mammary epithelial proliferation. A recent case‐control analysis of epithelial ER and PgR status reports an association of ER positive benign epithelium with the presence of cancer in the breast. Future research should include a systematic quantitative analysis of receptor expression in epithelial proliferative lesions, and the longitudinal follow‐up of women who have had receptor testing on benign breast t

ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00247.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Delay in breast cancer diagnosis continues to account for the highest percentage of medical malpractice cases. Two papers were reviewed concerning palpation and mammo‐graphic thresholds of detection and prognostic factor analysis for breast cancer. Most tumors were not palpated by experienced clinicians until the masses were larger than 15 mm. Mammograms are misinterpreted at a rate of 1.8%, and 7% of the mammograms are false negative with either palpable cancers or interval cancers developing. In a multivariate regression analysis, lymph node status was the most powerful predictor of disease, free survival (DFS), and tumor size added little to the model. Guidelines for the practicing physician and the medical legal system were offered from the data reviewe

ISSN:1075-122X    

DOI:10.1111/j.1524-4741.1995.tb00248.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY