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Biomedical subjects

L Bernstein

Publications and source records attributed to L Bernstein.

At least 73 records · Page 4Linked to original sources

HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas.

PURPOSE: The HER-2/neu gene codes for a membrane receptor protein that is homologous, but distinct from the epidermal growth factor receptor. This investigation was performed to validate fluorescence in situ hybridization (FISH) as a sensitive and specific method for assessing HER-2/neu gene amplification in archival tissue and to test whether this alteration is associated with poor prognosis. MATERIALS AND METHODS: HER-2/neu gene amplification was determined by FISH in 140 archival breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node-negative breast cancers was assessed for amplification by FISH to determine the utility of HER-2/neu gene amplification. RESULTS: Relative to solid-matrix blotting procedures, FISH analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers. Among patients treated by surgery only, the relative risks (relative hazard) of early recurrence (recurrent disease within 24 months of diagnosis), recurrent disease (at any time), and disease-related death were statistically significantly associated with amplification. The prognostic information contributed by HER-2/neu amplification was independent of the other markers studied. CONCLUSION: FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification in the absence of adjuvant therapy is an independent predictor of poor clinical outcome and is a stronger discriminant than tumor size. Women with small tumors that had gene amplification were at increased risk of recurrence and disease-related death.

Aged↗

Mesothelioma, asbestos, and reported history of cancer in first-degree relatives.

BACKGROUND: Although malignant mesothelioma is known to be strongly related to asbestos exposure, its relationship to familial factors is unclear. METHODS: We compared reported histories of cancer in first-degree relatives, obtained from telephone interviews with the next-of-kin of 196 patients who had a pathologic diagnosis of mesothelioma, and with those from 511 decreased controls. RESULTS: Among men exposed to asbestos, we found a statistically significant twofold elevation in the risk of mesothelioma for patients reporting cancer in two or more first-degree relatives. We found no significant elevation in women or among the small number of men without asbestos exposure. The next-of-kin of three patients (but no controls) reported a possible mesothelioma in a first-degree relative; asbestos exposure could not be ruled out in those relatives. Associations of asbestos with pleural mesothelioma were stronger among men with a reported family history of cancer than men without, although no statistical evidence of an interaction was detected. CONCLUSIONS: These results provide suggestive, but limited, evidence that a family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma given asbestos exposure.

Asbestos↗

Prealbumin in nutrition evaluation.

We compressed 16 test-pattern classes of albumin (ALB), cholesterol (CHOL), and total protein (TPR) in 545 chemistry profiles to 4 classes by converting decision values to a number code to separate malnourished (1 or 2) from nonmalnourished (NM) (0) patients, using as cutoff values for nonmalnourished (0), mild (1), and moderate (2): ALB 35, 27 g/L; TPR 63, 53 g/L; CHOL 3.9, 2.8 mmol/L; and BUN 9.3, 3.6 mmol/L. The BUN was found to have too low an S-value to make a contribution to the compressed classification. The cutoff values for classifying the data were assigned prior to statistical analysis, after examining information in the structured data. The data was obtained by a natural experiment in which the test profiles routinely done by the laboratory were randomly extracted. The analysis identifies the values for the variables used that best classify the data and are not dependent on distributional assumptions. The data were converted to 0, 1, or 2 as outcomes, to create a ternary truth table (each row is nnnn, the n value is 0 to 2). This allows for 3(4) (81) possible patterns, without the inclusion of prealbumin (PAB). The emerging system has much fewer patterns in the information-rich truth table formed (a purposeful, far from random, event). We added PAB, coded, and examined the data for 129 patients. The classes are a compressed truth table of n-coded patients with outcomes of 0, 1, or 2 with protein-energy malnutrition (PEM) increasing from an all-0 to all-2 pattern. Pattern class (F = 154), PAB (F = 35), ALB (F = 56), and CHOL (F = 18) were different across PEM class and predicted PEM class (R2 = 0.7864, F = 119, p < E-5). Kruskal-Wallis analysis of class by ranks was significant for pattern class (1E-18), PAB (6.1E-15), ALB (1E-16), CHOL (9E-10), and TPR (5.3E-13). The medians and standard error (SEM) for PAB, ALB, and CHOL of all four PABCLASSES (NM, mild, moderate, severe) are: PAB = 209, 8.7; 159, 9.3; 137, 10.4; 72, 11.1 mg/L, ALB = 36, 0.7; 30.5, 0.8; 25.0, 0.8; 24.5, 0.8 g/L; CHOL = 4.43, 0.17; 4.04, 0.20; 3.11, 0.21; 2.54, 0.22 mmol/L. PAB and CHOL values show the effect of nutrition support on PAB and CHOL in PEM. Moderately malnourished patients receiving nutrition support have PAB values in the normal range at 137 mg/L and at 159 mg/L when the ALB is at 25 g/L or at 30.5 g/L.

Biomarkers↗

Cancer among American-Samoans: site-specific incidence in California and Hawaii.

BACKGROUND: There is a paucity of data about cancer among American-Samoans, the largest Pacific Islander group after Hawaiians. This study provides the first data on the incidence and relative risk for all cancers among American-Samoans on the US mainland and in Hawaii. METHODS: The University of Southern California Cancer Surveillance Program and the Hawaii Tumor Registry, two population-based cancer surveillance programmes, provided archival data on American-Samoans residing in Los Angeles Country. California and in Hawaii, respectively. RESULTS: There were significant differences in the incidence and age-adjusted site-specific relative risk of cancers between American-Samoans, Hawaiians, and Anglos (non-Hispanic whites). In Hawaii, American-Samoans diagnosed with cancer compared with Hawaiians had a higher age-adjusted site-specific relative risk for cancers of the nasopharynx (especially males), liver, prostate, thyroid, and blood (especially females) and a lower relative risk for cancers of the colon, rectum (especially males), lung (especially females) and breast. Furthermore, compared with Anglos diagnosed with cancer in Hawaii, American-Samoans had a higher relative risk for cancers of the nasopharynx (especially males), stomach, liver, lung (especially males), corpus uteri, thyroid and blood, and a lower relative risk for cancers of the colon, skin, breast, testes, cervix uteri, bladder (especially males), and lymph nodes. A relatively similar profile of cancer distribution and relative risk was observed among American-Samoans and Anglos diagnosed with cancer in California. CONCLUSIONS: The data provide baseline information which has important implications for future cancer control research and prevention in this population.

Adolescent↗

Epidemiology and prevention of breast cancer.

Breast cancer is the most common cancer in women, accounting for 32% of all newly diagnosed cancers. Demographic characteristics associated with an increased risk include increasing age, birth in North America or northern Europe, high socioeconomic status, never having been married, and, for breast cancer diagnosed after 45 years of age, the white race. Early age at menarche, late age at menopause, late age at first full-term pregnancy, and low parity increase risk, while removal of the ovaries at an early age is protective. Obesity increases risk in postmenopausal women. Having a first degree relative with breast cancer confers an increased risk, especially if both a mother and a sister have had breast cancer at an early age. Mutations in the BRCA1 and BRCA2 genes are associated with an inherited susceptibility to breast cancer at an early age. Other markers of increased risk include atypical and hyperplastic epithelial cells in nipple aspirate fluid, nodular densities on mammogram, and biopsy-confirmed benign proliferative breast disease. Little can be done at present to reduce breast cancer risk through primary prevention, but secondary prevention by mammographic screening in women of age 50 and older reduces mortality from breast cancer.

Adult↗

Measurement of organochlorine levels in postprandial serum or in blood collected in serum separator tubes.

Whether organochlorine blood levels in fasting and postprandial specimens provide equivalent measures of exposure and the extent to which collecting blood in tubes containing material to separate serum and blood cells corrupts the specimen are unclear. In this paper, we present data from two studies that address both of these issues. In the first study, 27 women provided fasting blood in plain, silicone-coated Vacutainer tubes (red-topped) and in similar tubes containing serum separator gel (SSTs), as well as a postprandial specimen in a red-topped tube. The specimens collected in SSTs were left to stand overnight, with the gel in contact with the sample. In the second study, the blood of 12 industrial incinerator workers was collected in red-topped tubes and in SSTs. Blood in SSTs was left in contact with the gel for 5 days. Serum organochlorine residue levels ([1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] (DDE)) and polychlorinated biphenyls) in samples collected in red-topped tubes were highly correlated with levels measured in samples collected in SSTs (all Pearson r values were > or = 0.79). Postprandial and fasting organochlorine levels were also highly correlated (Pearson r values > or = 0.89). Our results indicate that timing of the collection of blood in relation to meals and use of SSTs to collect blood specimens did not greatly affect the relative classification of subjects with respect to serum level of DDE or polychlorinated biphenyls. The longer the specimen was in contact with the SST gel, however, the lower the level of organochlorine that was detected and, at least for DDE, the greater the misclassification caused.

Adult↗

Risk factors for in situ breast cancer.

Few data exist on risk factors for in situ breast carcinoma. We examined risk factors for in situ breast carcinoma in data from two population-based case-control studies of breast cancer conducted among female residents of Los Angeles County. Cases with in situ or invasive disease were identified through the cancer registry for Los Angeles Country in the 1980s. We included all cases ages 40 years or younger diagnosed over a 5.5-year period and all cases ages 55-64 years diagnosed over a 3-year period. Control subjects were individually matched to cases by age (+/-3 years), neighborhood of residence, and, for younger controls, parity (nulliparous versus parous). The analysis included 233 cases with in situ cancer, 2057 cases with invasive cancer, and 2203 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for screening mammography and established risk factors. In general, risk factors for in situ breast cancer were similar to those for invasive disease in this population. In premenopausal women, however, the risk of in situ breast cancer decreased with increasing body mass index, whereas for invasive disease, body mass index was unrelated to risk. In addition, in postmenopausal women with known age at menopause, use of unopposed estrogen replacement therapy was associated with increased risk of in situ disease [OR for ever use of estrogen alone was 1.60 (95% CI, 1.00-2.58)], whereas for invasive disease the OR was 1.23 (95% CI, 1.00-1.50). A similar difference was seen for combined hormone replacement therapy. Unmeasured increased screening among estrogen or combined replacement hormone users compared with nonusers could account for some of the association of in situ breast cancer risk with hormone replacement use.

Adult↗

Role of zidovudine antiretroviral therapy in the pathogenesis of acquired immunodeficiency syndrome-related lymphoma.

The role of zidovudine and other antiretroviral agents in the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related lymphomas has been somewhat controversial. In an attempt to elucidate the precise role of antiretroviral agents in the subsequent development of AIDS-related lymphoma, we performed a population-based, case-control study of human immunodeficiency virus (HIV)-seropositive patients with intermediate- or high-grade lymphoma in Los Angeles County, California, in which information regarding use of antiretroviral medications was ascertained. Diagnostic biopsy material was reviewed to confirm intermediate-or high-grade lymphoma. A structured interview, conducted with all cases and controls, included information about use of zidovudine and other antiretroviral agents. A total of 112 HIV-infected homosexual/bisexual men with lymphoma were matched to 112 homosexual/bisexual men with asymptomatic HIV infection; 49 of the lymphoma cases were also matched to 49 additional controls with AIDS, as defined by conditions other than lymphoma. Positive histories of zidovudine use were reported by 44 (39%) lymphoma cases, 24 (21%) asymptomatic HIV controls, and 21 (42%) AIDS controls. The average duration of zidovudine use up to 12 months before lymphoma diagnosis was 19.0 +/- 13.0 months (mean +/- SD) for the lymphoma cases, 12.6 +/- 10.5 months for the asymptomatic controls, and 11.0 +/- 7.1 months for the AIDS controls. When comparing the 49 HIV-positive lymphoma cases with their 49 matched AIDS controls, all of whom were diagnosed with AIDS during the same time period, the matched relative odds of lymphoma associated with prior use of zidovudine was 0.43 (95% confidence interval [CI] = 0.17 to 1.12). In comparing all 112 lymphoma cases with 49 AIDS controls, the unmatched relative odds of lymphoma associated with zidovudine use was 0.93 (95% confidence interval = 0.47 to 1.83). One lymphoma case and no AIDS control cases had a history of didanosine use; no lymphoma case or AIDS control cases had taken zalcitabine. We conclude that zidovudine is not associated with an increased risk of development of lymphoma among HIV-infected homosexual or bisexual men.

Acquired Immunodeficiency Syndrome↗

Cancer incidence among Filipinos in Los Angeles County, 1972-1991.

Although Filipinos are the second largest Asian subgroup in the United States, little is known about their patterns of cancer incidence. We have examined cancer incidence rates among Filipinos living in Los Angeles County from 1972 through 1991 and evaluated their risk of non-localized cancer relative to non-Hispanic whites. Although Filipinos have substantially lower cancer rates than non-Hispanic whites in Los Angeles County, their incidence rates of liver cancer, cancer of the nasopharynx and thyroid cancer are higher. Filipino men and women had somewhat more advanced cancer at diagnosis, on average, than non-Hispanic whites, though no statistically significant differences were observed for sites where early detection methods exist. Our data suggest that Filipino-Americans would benefit from increased screening for cervical and breast cancer as well as efforts to interrupt transmission of hepatitis B virus to reduce liver cancer incidence.

Aged↗

Correlation of estrogen levels between successive pregnancies.

To date, no study has attempted to correlate hormone levels between successive pregnancies in the same woman. Serum levels of total estradiol and total free estradiol have been measured between the eighth and the 17th weeks in the first and second full-term pregnancies of 34 white women participating in the Collaborative Perinatal Study, 1959-1965. Intraindividual interpregnancy Pearson's product moment correlations were calculated. Partial correlation coefficients (adjusted for gestational age) for log pregnancy total estradiol and total free estradiol were 0.78 and 0.73, respectively (p < 0.001). These findings provide evidence that levels of pregnancy estradiol are significantly and strongly correlated in successive pregnancies of the same woman. This phenomenon can provide an explanation for the higher concordance of breast cancer incidence between two sisters than between a mother and daughter in the familial pattern of breast cancer.

Breast Neoplasms↗

Incidence of second cancers in patients treated for Hodgkin's disease.

BACKGROUND: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies have indicated that the incidence of certain solid tumors increases following treatment for Hodgkin's disease. PURPOSE: We studied the association between treatment for Hodgkin's disease and the incidence of second cancers. METHODS: We conducted a study within a cohort that included 10,472 patients from 14 cancer centers in the United States and Canada who were first diagnosed as having Hodgkin's disease at some point from 1940 through 1987. Discounting the 1st year after diagnosis, the average length of follow-up was 7.1 years per subject. RESULTS: We observed 122 leukemias and 438 solid tumors. The relative risk (RR) of leukemia following chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI] = 5.6-35). Increased risks of leukemia were observed after treatment with chlorambucil (RR = 2.0; 95% CI = 1.1-3.6), procarbazine (RR = 4.9; 95% CI = 2.6-9.1), vinblastine (RR = 1.7; 95% CI = 1.1-2.8), and a group of rarely used drugs that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI = 1.9-7.4). RRs were also estimated for various combinations of drugs, including MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95% CI = 2.9-12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (RR = 1.5; 95% CI = 0.7-3.4). The RR of leukemia associated with splenectomy was 1.6 (95% CI = 1.0-2.5). The RR of solid tumors following chemotherapy was 1.4 (95% CI = 1.1-1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1 (95% CI = 1.7-5.8). Chemotherapy was associated with an increased risk of cancers of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI = 1.7-20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1-3.2). In patients followed for 10 or more years after radiotherapy, increased risks were found for cancers of the respiratory system and intrathoracic organs (RR = 2.7; 95% CI = 1.1-6.8) and for cancers of the female genital system (RR = 2.4; 95% CI = 1.1-5.4). CONCLUSIONS: Procarbazine, chlorambucil, and vinblastine are associated with increased leukemia risk. Combination drug regimens have leukemogenic effects estimated as the product of RRs for individual drugs. Chemotherapy and radiotherapy increase the risk of selected solid tumors, and the effect of chemotherapy on solid tumor risk is weaker than the leukemogenic effect. IMPLICATIONS: Without doubt, the benefits of treatment of Hodgkin's disease outweigh the risk of a subsequent malignancy, but data on the carcinogenic effects of radiation and drugs beyond 10 years after treatment continue to be sparse, and future analyses should be directed at long-term survivors.

Adolescent↗

Prostate cancer: trends in mortality and stage-specific incidence rates by racial/ethnic group in Los Angeles County, California (United States).

Between 1976 and 1988 in the United States, the secular trends to age-adjusted incidence rates of prostate cancer were significantly different by racial/ethnic group (P < 0.001), and increased significantly only among non-Hispanic Whites at a rate of 2.7 percent (95 percent confidence interval [CI] = 2.3-3.1%) annually. While incidence rates of regional disease increased significantly (7.7 percent to 11.3 percent annually) among all racial/ethnic groups during this period, localized disease increased significantly only among non-Hispanic Whites, by 1.8 percent (CI = 1.4-2.3%) annually. Prostate cancer mortality in Los Angeles County (California) remained constant among Hispanics, non-Hispanic Whites, and Asians, but increases 1.6 percent (CI = 0-3.2%) annually among Blacks. While the increase in localized disease rates of non-Hispanic Whites may be due to increased detection of asymptomatic disease, this apparently has not occurred among other racial/ethnic groups in Los Angeles County. The secular increase in regional disease rates among all racial/ethnic groups without a concurrent increase in mortality (except Blacks), suggests increased accuracy of staging rather than a true increase in incidence may account for these trends. Adjusted for socioeconomic status, year and age at diagnosis, Black and Hispanic men were at significantly higher risk of being diagnosed with non-localized disease (odds ratio = 1.39 and 1.24, respectively) than were non-Hispanic Whites.

Black or African American↗