Update of the NCCN guidelines for treatment of prostate cancer.
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Androgens↗
Biomedical subjects
R Millikan
Publications and source records attributed to R Millikan.
The role of chemotherapy in the management of the patient with T3b bladder cancer.
At present, it is clear that chemotherapy can contribute to improved outcome for some patients with locally advanced bladder cancer. For patients in clinical stage T3b, the incidence of pathological node involvement is no high that little is lost by giving up precise staging, and neoadjuvant therapy is probably the preferred approach. This is based on improved tolerance for chemotherapy, improved resectability rates, and the desirability of addressing metastatic disease at the earliest opportunity. Although more experience is needed, at present the surgical complication rate for cystectomy after chemotherapy does not appear to be significantly higher than immediate surgery. For patients thought to have T2/3a lesions according to clinical evaluation who are subsequently found to have stage pT3b at operation, the evidence for benefit from chemotherapy is not yet conclusive, and we consider use of adjuvant therapy in this setting to be investigational. It is hoped that refinement of clinical markers and continued improvement in combination regimens will allow more effective therapy to be targeted more selectively in the future.
Antineoplastic Combined Chemotherapy Protocols↗
The Carolina Breast Cancer Study: integrating population-based epidemiology and molecular biology.
The integration of epidemiology and molecular biology provides a new strategy to identify additional risk factors for breast cancer and to better understand the role played by traditionally recognized risk factors. The Carolina Breast Cancer Study (CBCS) is a population-based, case-control study designed to identify causes of breast cancer among Caucasian and African-American women who are residents of a 24-county area of central and eastern North Carolina. Information on established and potential breast cancer risk factors is obtained by personal interviews. Blood samples are collected from all consenting participants. Medical record documentation and paraffin-embedded tumor specimens are obtained for all breast cancer patients. DNA from tumor tissue is tested for a variety of molecular alterations characteristic of breast cancer. Germline DNA from blood lymphocytes is evaluated for presence of alleles increasing susceptibility to breast cancer. Statistical analyses evaluate gene-environment interaction by exploring the associations between environmental/behavioral factors and breast cancer in relation to specific molecular alterations (germline and tumor). Results will help identify high-risk women, clarify causal pathways, and hopefully contribute to the prevention of breast cancer.
Adult↗
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.
Breast Neoplasms↗
Studying environmental influences and breast cancer risk: suggestions for an integrated population-based approach.
Increased attention has focused in recent years on environmental exposures which may elevate risk of human breast cancer. Following a brief introduction to the topic, we present a summary of recent evidence regarding the role of chlorinated hydrocarbons (e.g. pesticides), occupational exposures (e.g. electromagnetic fields), dietary factors, and other hydrocarbons (e.g. tobacco). Next, we present suggestions for additional measurements which may help to clarify the contribution of environmental factors, including individual and ecologic level exposure histories, polymorphisms in carcinogen-metabolizing enzymes, and interactions among environmental exposures, breast tumor characteristics, and other risk factors for breast cancer. Finally, we discuss how a population-based approach may be used to integrate these sources of information and could provide new clues regarding the role of environmental influences in breast cancer.
Breast Neoplasms↗
p53 mutations in benign breast tissue.
PURPOSE: Patients with benign breast biopsies that exhibit atypical epithelial proliferation or fibroadenoma may be at increased risk for invasive breast cancer. We hypothesized that molecular markers might also be useful to evaluate the malignant potential of nonneoplastic breast tissue. PATIENTS AND METHODS: Study subjects belonged to a cohort of 6,805 women who underwent biopsy for nonmalignant breast disease at the Mayo Clinic and Rochester-affiliated hospitals between 1967 and 1981. As part of a nested case-control study that compared subjects who developed invasive breast cancer with those who did not, we analyzed a sample of 60 benign breast biopsies for the following markers: HER-2/neu and p53 over-expression by immunohistochemistry, HER-2/neu and PRAD-1 amplification using differential polymerase chain reaction (PCR), and p53 mutation using single-strand conformation analysis (SSCA) and direct DNA sequencing by asymmetric PCR. RESULTS: None of 60 biopsies showed amplification of HER-2/neu or PRAD-1. Five samples exhibited low-level immunoreactivity to the HER-2/neu protein product. Fourteen samples exhibited focal or diffuse immunoreactivity to the p53 protein. Point mutations in the p53 gene were found in five samples: three of these samples exhibited mutations that altered the amino acid sequence. Only two of five samples with p53 mutation exhibited p53 overexpression. Histologic diagnoses on three samples with nonconservative p53 mutation were, respectively, nonproliferative fibrocystic change, papillomatous hyperplasia, and fibroadenoma. CONCLUSION: The clinical significance of p53 mutation, p53 overexpression, and low-level HER-2/neu expression in benign breast tissue remains to be determined. Further research will be necessary to evaluate whether these markers could serve as useful adjuncts to histology in evaluation of the malignant potential of benign breast tissue.
Base Sequence↗
Linkage analysis of DRD2, a marker linked to the ataxia-telangiectasia gene, in 64 families with premenopausal bilateral breast cancer.
Recent reports suggest that subjects who are heterozygous for the ataxia-telangiectasia gene are at increased risk of breast cancer. We conducted linkage analyses of 64 families with premenopausal bilateral breast cancer using DRD2, a marker linked to the ataxia-telangiectasia locus at 11q22-23. We assumed a model with dominant transmission of breast cancer. Lod scores summed over all families provided strong evidence against tight linkage (e.g., a lod score of -6.08 at theta = 0.00001), although a single family provides suggestive evidence of tight linkage to DRD2. Evidence against linkage to 11q was strongest among families that may involve the BRCA1 breast cancer susceptibility gene on 17q21. However, we did not observe evidence of linkage to 11q among the remaining subgroup with neither a family history of ovarian cancer nor the appearance of linkage to 17q21.
Adult↗
A linkage analysis of D17S74 (CMM86) in thirty-five families with premenopausal bilateral breast cancer.
We report here results of a linkage analysis of a marker in 35 families in which the proband had premenopausal bilateral breast cancer. This group is of particular interest given their high family risk and the question of etiological heterogeneity. Probands were ascertained from cancer registries in Los Angeles County and Connecticut and major hospitals in Montréal and Québec. Assuming no residual heterogeneity and summing lod scores over all families, we obtained strong evidence against tight linkage (e.g., lod score at theta = 0.000001 is -3.39). To address the issue of heterogeneity, we performed admixture and predivided sample analyses. Using an admixture model we were able to reject the hypothesis of no linkage versus that of linkage with homogeneity (P = 0.045). However, we were unable to reject the hypothesis of no linkage versus linkage with heterogeneity (P = 0.119) or to distinguish between linkage with homogeneity and linkage with heterogeneity (P = 0.500). Predivided sample analyses based upon age of onset, pathological characteristics, time between diagnoses of the breast cancers in each bilateral proband, and the span of ages at diagnoses within a family did not discriminate between apparently linked and unlinked families.
Age Factors↗
Simian virus 40 small tumor antigen and an amino-terminal domain of large tumor antigen share a common transforming function.
The 82-residue amino-terminal sequences of simian virus 40 large tumor antigen (TAg) and small tumor antigen (tAg) are identical. Genetic analysis of TAg lacking amino acids 1-82 revealed that it was transformation-defective, as revealed by the agar growth assay, except when introduced in the presence of tAg. Since the latter, alone, lacks overt transforming activity, it would appear that the function of the sequence common to TAg and tAg is necessary, but not sufficient, for TAg transforming activity and that tAg can provide that function or its equivalent in trans. Thus, tAg may, in part, be viewed as a "portable" copy of a TAg functional domain.
Animals↗
Attitudes toward genetic testing in patients with colorectal cancer.
PURPOSE: The purpose of this study was to examine risk perceptions and interest in genetic testing among African American and White patients with colorectal cancer. DESCRIPTION OF STUDY: In this cross-sectional study, 98 patients with colorectal cancer participated in a brief structured telephone interview. Information was collected on knowledge and risk perceptions regarding colorectal cancer genetics, health behaviors, knowledge about the availability of genetic testing, and interest in genetic testing for colorectal cancer susceptibility. RESULTS: Sixty-one percent of the participants were worried about their relatives' risk of colorectal cancer, and 64% were concerned about being a colorectal cancer susceptibility gene carrier. Although 81% of the participants reported that they had never heard about a genetic test for colorectal cancer susceptibility, 72% stated that they would want to take the test if it were available. Predictors of intention to have a genetic test were younger age, less advanced stage of disease, and more frequent thoughts about colorectal cancer being hereditary. CLINICAL IMPLICATIONS: These results suggest that the demand for genetic testing may be great, despite a general lack of knowledge about colorectal cancer genetics and the potential risks and limitations of testing. Education and counseling about cancer genetics and genetic testing may clarify misconceptions about hereditary colorectal cancer and help patients with colorectal cancer and their family members make informed decisions about whether to undergo testing.
Adult↗