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Biomedical subjects

I J Bleiweiss

Publications and source records attributed to I J Bleiweiss.

At least 19 recordsLinked to original sources
PubMed1998

Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients.

Based on breast cancer families with multiple and/or early-onset cases, estimates of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may be as high as 85%. The risk for individuals not selected for family history or other risk factors is uncertain. We determined the frequency of the common BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268 anonymous Ashkenazi Jewish women with breast cancer, regardless of family history or age at onset. DNA was analyzed for the three mutations by allele-specific oligonucleotide hybridization. Eight patients (3.0%, 95% confidence interval [CI] 1.5%-5.8%) were heterozygous for the 185delAG mutation, two (0.75%, 95% CI 0.20-2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT mutation. The lifetime risk for breast cancer in Ashkenazi Jewish carriers of the BRCA1 185delAG or BRCA2 6174delT mutations was calculated to be 36%, approximately three times the overall risk for the general population (relative risk 2.9, 95% CI 1.5-5.8). For the 5382insC mutation, because of the low number of carriers found, further studies are necessary. The results differ markedly from previous estimates based on high-risk breast cancer families and are consistent with lower estimates derived from a recent population-based study in the Baltimore area. Thus, presymptomatic screening and counseling for these common mutations in Ashkenazi Jewish women not selected for family history of breast cancer should be reconsidered until the risk associated with these mutations is firmly established, especially since early diagnostic and preventive-treatment modalities are limited.

Adult↗
PubMed1998

The efficacy of neoadjuvant chemotherapy compared to postoperative therapy in the treatment of locally advanced breast cancer.

The current approach to the treatment of locally advanced breast cancer is sequential chemotherapy, surgery and/or radiation, and consolidation chemotherapy. Although significant tumor response is seen with this regimen, there are few studies that compare this approach to postoperative chemotherapy. The purpose of this study was to compare the disease-free and overall survival of patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and surgery to patients treated with surgery followed by adjuvant chemotherapy. Ninety-four patients with stage IIB, IIIA, and IIIB breast cancer were treated with a standardized chemotherapy regimen. The first group, 60 patients who were followed prospectively, was treated with neoadjuvant chemotherapy (NCT) consisting of vincristine, prednisone, cytoxan, methotrexate, and 5-FU (CVFMP) followed by surgery and consolidation chemotherapy with adriamycin. The second group, 34 patients evaluated retrospectively, had surgery followed by postoperative chemotherapy (PCT) with CVFMP followed by adriamycin. Overall median follow-up was 38 months. In the NCT group, 45/60 (75%) patients had a clinical response to induction therapy and the median reduction in tumor size was 50%. The rates of local recurrence, distant recurrence, and death from disease were similar in the two groups. The time to local recurrence was similar for the two groups. However, the median time to distant recurrence was shorter in the NCT group (19 month vs. 31 months, p = NS). Overall median survival among the NCT patients was shorter than for the PCT group (30 vs. 47 months, p = NS). The current study suggests that postoperative therapy is comparable to a neoadjuvant regimen in patients with locally advanced breast cancer with regard to local recurrence, distant recurrence, and overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Nucleolar localization of BRCA1 protein in human breast cancer.

Both a rabbit polyclonal BRCA1 antibody, K-18, and a mouse monoclonal BRCA1 antibody, AP 16, produced nucleolar epithelial cell staining on frozen tissue sections of human infiltrating mammary carcinomas. There was much less BRCA1 antibody staining in normal tissues; however, 2 intraductal tumors and a papilloma, found in proximity to the carcinomas showed considerable nucleolar immunoreactivity. MCF-7 cells fixed in methanol and immunostained with the same two antibodies also revealed nucleolar staining, however, after 4% paraformaldehyde fixation for three minutes, there were many fewer nuclei stained. Antigen retrieval methods on formalin-fixed, paraffin-embedded specimens produced tumor cell cytoplasmic staining with AP 16 and nuclear staining in both tumor and normal epithelial cells with another BRCA1 monoclonal antibody, SG 11.

Adult↗
PubMed1998

CYP17 genotype and breast cancer risk.

The MspAI polymorphism in the 5' untranslated region of CYP17 has been evaluated as a breast cancer risk factor in a hospital-based case-control study in New York City. The study population consisted of 363 women [123 breast cancer patients and 240 patient controls (123 benign breast disease without atypical hyperplasia, 117 women without breast disease)]. There were 224 Caucasians (76 cases, 148 controls), 55 African-Americans (20 cases, 35 controls) and 84 Hispanics (27 cases, 57 controls); 142 premenopausal women and 221 postmenopausal women. Consistent with a previous report (Feigelson et al., Cancer Res., 57: 1063-1065, 1997) we found no evidence to implicate the minor variant (restriction site present allele, designated A2) as a breast cancer risk factor. Furthermore, we sought evidence to implicate the minor variant of CYP17 in the development of more aggressive breast cancers (n = 38/121) as had been reported previously. Although confidence intervals (CI) overlap, the data presented here do not provide support for previously reported findings (odds ratio, 0.9; 95% CI, 0.4-2.0; n = 38 versus odds ratio, 2.5; 95% CI, 1.1-5.2; n = 40). Clearly this question needs to be resolved in a larger study. No evidence was found to support the contention that inheritance of the minor variant is a predictor of early age at menarche. Allelic frequencies between different ethnic groups were not found to be different with the exception of Hispanic controls, in which the genotypic distribution was not consistent with the Hardy-Weinberg equilibrium.

Black People↗
PubMed1997

p53 haplotype determination in breast cancer.

Inheritance of certain germ line haplotypes consisting of three biallelic polymorphisms of p53 has been proposed as a risk factor for breast cancer and colorectal cancer [A. Själander et al., Carcinogenesis (Lond.), 17: 1313-1316, 1996, and Carcinogenesis (Lond.), 16: 1461-1464, 1995]. In their studies, pairwise haplotypes of these three polymorphisms were estimated. Extended haplotypes were further projected from the pairwise combinations. To overcome the necessity to estimate pairwise and extended haplotype frequencies, a PCR method has been developed to determine the absolute extended p53 haplotypes in diploid genomes. The method requires allele-specific PCR, confirmed by restriction analysis, and successive amplicon analysis. It has been applied to a nested case-control study of breast cancer (284 subjects; 99 cases and 185 controls; 182 Caucasians, 56 Hispanics, and 46 African-Americans). Evidence is presented that minor variants of the intron 3, codon 72, and intron 6 polymorphisms were moderately elevated in Caucasian breast cancer cases (intron 3, P = 0.03 for genotype and P = 0.01 for allelic frequency; codon 72, P = 0.07 for genotype and P = 0.054 for allelic frequency; and intron 6, P = 0.02 for genotype and P = 0.02 for allele frequency). Accordingly, analysis of haplotype distributions suggested an association of minor p53 haplotypes with breast cancer risk in Caucasians (P = 0.07). The relative allelic frequencies in breast cancer cases compared with controls also differed by age and menopausal status; the 1-2-1 haplotype was overrepresented in postmenopausal cases (P = 0.02) and cases older than 50 years (P = 0.02), whereas the other minor haplotypes (1-1-2 and rare variants) were overrepresented in premenopausal cases (P = 0.003) and cases 50 years of age and younger (P = 0.02). Genotype distributions at each locus and for all control groups were consistent with Hardy-Weinberg equilibria. Differences in haplotype distribution were associated with ethnicity (Caucasians versus African-Americans and Caucasians versus Hispanics, P < 0.001). The new haplotyping method may be useful in the study of gene-environment interactions.

Adult↗
PubMed1997

Factors associated with clear biopsy margins and clear reexcision margins in breast cancer specimens from candidates for breast conservation.

BACKGROUND: The aim of this study was to identify variables associated with clear biopsy margins and clear reexcision margins of breast cancer specimens from patients who are candidates for breast conservation. STUDY DESIGN: The records of breast cancer patients were reviewed to identify candidates considered for breast conservation after biopsy. Factors associated with obtaining histopathologically clear excisional biopsy margins and clear reexcision margins were studied in 674 excisional biopsy specimens and in 197 reexcision specimens. RESULTS: Clear biopsy margins were associated with older patient age (p = 0.0446), family history of breast cancer (p = 0.0008), diagnosis by fine needle aspiration (p = 0.0000), small tumor size (p = 0.0010), absence of ductal carcinoma in situ (p = 0.0004), and absence of extensive intraductal carcinoma (p = 0.0117). In multivariate analysis, only diagnosis by fine needle aspiration and small tumor size were associated with clear biopsy margins. Clear margins in reexcision specimens were associated with small tumor size (p = 0.0086), close or unknown biopsy margins (p = 0.0003), and absence of nodal involvement (p = 0.0014). In multivariate analysis only biopsy margin status and node status were associated with clear reexcision margins. CONCLUSIONS: These data indicate that obtaining clear biopsy margins is facilitated by small tumor size and by having a preoperative diagnosis by fine needle aspiration. The majority of patients undergoing reexcision will have clear margins although this is significantly less likely when the biopsy margins are involved or when nodal involvement is present.

Biopsy↗
PubMed1996

Defective expression of cellular retinol binding protein type I and retinoic acid receptors alpha2, beta2, and gamma2 in human breast cancer cells.

Because the retinoic acid (RA) signaling pathway regulates cell proliferation and differentiation, inactivation of genes integral to the pathway represents a potential mechanism of carcinogenesis. We have studied in human breast cancer cells (T47D, MCF-7, ZR75-1, MDA-MB-231, and BT20) the expression of a subset of retinoid signaling genes that are themselves transcriptionally up-regulated by RA, the cellular retinol binding protein type I (CRBPI) and the RA receptors (RARs) alpha2, beta2, and gamma2. We find that constitutive expression of these genes is low or undetectable, and that expression levels are seldom responsive to 24 h treatment with 1 microM all-trans or 9-cis RA (Northern blot analysis). This is in contrast to breast fibroblasts, which show RA-dependent expression of all four genes under the same conditions. Moreover, normal human breast epithelial cells express CRBPI and RARbeta2 at the mRNA level, suggesting that loss of expression of these genes is tied to malignant transformation. RARbeta2, but not CRBPI, was also expressed in RA-treated MTSV1-7 cells, an immortalized but nontumorigenic luminal epithelial cell line. Lack of CRBPI and RARbeta2 expression in cancer cells was not due to general impairment of RA signaling, as shown by RA activation of a RARE3-tk-CAT reporter in a subclone of MDA-MB-231 cells that did not express either CRBPI or RARbeta2. These results suggest that at least two independent defects in the expression of proteins that function in retinoid signaling may be involved in breast carcinogenesis.

Breast Neoplasms↗
PubMed1996

Epithelioid cells in myoid hamartoma of the breast: a potential diagnostic pitfall for core biopsies.

OBJECTIVE: We report six cases of myoid hamartoma of the breast, a rare benign lesion in which the characteristic smooth muscle cells may have epithelioid histology. We emphasize the importance of radiographic correlation and immunohistochemical studies to diagnosis, particularly on stereotactic core biopsies, to avoid potential confusion with infiltrating lobular carcinoma. DESIGN: Case studies. Prospective and retrospective analysis of six cases, including stereotactic biopsy of two. SETTING: Academic medical center-based pathology practice. PATIENTS: Six postmenopausal women, aged 50 to 59 years, with palpable or nonpalpable mammographically evident breast masses. RESULTS: All the lesions were radiographically well circumscribed, most showing heterogeneous radiodensity. Histologically variable amounts of glandular, fibrous, and adipose tissue were admixed with smooth muscle cells, which occasionally had prominent epithelioid features. All the lesions' myoid cells stained for smooth muscle markers as well as steroid receptor proteins. Stereotactic core biopsy was diagnostic in one case, making excision unnecessary. CONCLUSIONS: With proper radiographic correlation and immunohistochemical confirmation, myoid hamartoma can be confidently diagnosed even on the limited tissue samples yielded by stereotactic core biopsy.

Basement Membrane↗
PubMed1995

Detection of mammary tumor virus env gene-like sequences in human breast cancer.

Mouse mammary tumor virus (MMTV) has been related to human breast cancer (BC) in previous studies. Although suggestive sequence homology to MMTV has been described in BC DNA, the presence of human endogenous retroviruses (HERs) confounded these results. We have selected a 660-bp sequence of the MMTV env gene with very low homology to HER or to any other human or viral gene. We have searched for sequences homologous to it using the polymerase chain reaction. DNA was extracted from fresh or frozen tissues using primers and probes constructed to detect 660 bp; for paraffin-embedded tissues, we sought 250-bp sequences by similar methodology. The 660-bp sequence was detected in 121 (38.5%) of the 314 unselected BC samples, in cultured BC cells, in 2 (6.9%) of 29 breast fibroadenomas and in 2 (1.8%) of 107 breast specimens from reduction mammoplastias. The sequence was not found in normal tissues including breast, lymphocytes from BC patients, nor in other human cancers or cell lines. The 250-bp sequence was detected in 60 (39.7%) of the 151 BCs, and in 1 of 27 normal breast samples assayed from paraffin-embedded sections. Cloning and sequencing of the 660 bp and 250 bp demonstrated that they are 95-99% homologous to MMTV env gene, but not to the known HERs nor to other viral or human genes (< 18%). Southern blot analysis using labeled cloned sequences showed that the 660-bp sequences were present in low copy number as a 7-8-kb EcoRI fragment only in breast cancer samples and two breast cancer cell lines that were positive by PCR. These data indicate that 38-40% of human breast cancers contain gene sequences homologous to the MMTV env gene that are absent from other tumors and tissues. These MMTV env gene-like sequences may play a role in the etiology of a large proportion of human breast cancer.

Base Sequence↗
PubMed1995

Contralateral axillary lymph node metastasis as the first evidence of locally recurrent breast carcinoma.

BACKGROUND: Carcinoma of the breast infrequently presents initially as axillary adenopathy. In such cases, after biopsy proves the presence of metastatic carcinoma, the primary tumor generally is assumed to be in the ipsilateral breast, despite negative mammographic findings and the lack of a clinically palpable breast mass. METHODS: The authors recently studied a case of a 50-year-old woman in whom recurrent neuroendocrine carcinoma of the breast presented as a contralateral axillary lymph node metastasis. After mastectomy ipsilateral to the metastasis proved negative for tumor, a histologic comparison of the previous contralateral tumor with that in the lymph node was performed, followed by biopsy of the clinically and mammographically negative original lumpectomy site. RESULTS: Histologic and immunohistochemical studies proved that the original, metastatic, and locally recurrent tumors were identical, sharing unusual neuroendocrine features. The patient is currently disease free after chemotherapy. CONCLUSION: Contralateral mammary carcinoma should be considered in the workup of a patient who presents with evidence of an axillary lymph node metastasis. Locally recurrent breast carcinoma may be clinically and mammographically occult. Histologic review of prior biopsy material and comparison with current tissue is essential in proper patient management.

Axilla↗
PubMed1994

Adoptive cellular therapy of human breast and colorectal tumor targets using ex vivo activated memory T lymphocytes with potentiation by cis-diamminedichloroplatinum(II).

Autolymphocyte therapy (ALT) is adoptive cellular therapy of cancer using ex vivo activation of autologous peripheral blood lymphocytes (PBL). Memory T cells are the principal effector population in ALT, with in vivo activity in patients with metastatic renal cell carcinoma (RCC) and melanoma, and ex vivo cytotoxicity against autologous tumor targets. However, the noncytolytic lymphocyte portion of ex vivo-activated memory T cells (ALT cells) may also contribute as antitumor effectors. Pretreatment of murine and human tumor cells ex vivo with chemotherapeutic agents can enhance their susceptibility to antitumor lymphocytes ex vivo and in vivo. To determine whether cis-diamminedichloroplatinum(II) (DDP) could enhance ex vivo antitumor effects of ALT cells by immunomodulation, human breast and colorectal carcinoma target cells were derived from both primary and metastatic surgical specimens and incubated in complete medium (CM) with DDP or in CM alone (control group). Viability of each group was confirmed by trypan blue-dye exclusion test. ALT cells were prepared from autologous PBL at surgery. Primary and metastatic tumor cells from each group were used as targets for ALT cells and levels of interferon-gamma (IFN-gamma) release were measured as a determination of antitumor effect and recognition. Primary tumor target cells incubated in DDP showed enhanced antitumor effects and recognition by autologous ALT cells, as measured by the IFN-gamma assay compared to non-DDP-treated controls. Metastatic autologous tumor target cells demonstrated less IFN-gamma release than did the primary targets, although this was enhanced by pre-treating metastatic tumor targets with DDP. ALT cells demonstrated minimal IFN-gamma release when incubated with allogeneic tumor targets. These data suggest that autotumor recognition of metastatic tumor targets is comparable to that of primary lesions following ex vivo pretreatment of metastatic cells with nonlethal doses of certain chemotherapeutic agents. DDP may somehow alter the physical properties of target cells, rendering them susceptible to immune-mediated attack and the combination of ALT and DDP may lead to increased therapeutic efficacy in patients with metastatic breast and colon cancer.

Breast Neoplasms↗
PubMed1994

Silicone breakdown and capsular synovial metaplasia in textured-wall saline breast prostheses.

Saline-filled prostheses are currently the only type of prostheses available for cosmetic use in the United States because of concerns raised about the possibility of systemic toxicity of silicone-filled artificial mammary implants. Although the approved implants are saline-filled, their potential to release silicone particles from the shells has not been systematically evaluated. We performed microscopic examination of the pericapsular tissue of 54 patients with textured-surface implants and compared these with 51 patients with smooth-walled implants over a 2-year period. The capsules that had formed around virtually all textured-surface implants had silicone fragments present either in extracellular spaces, in vacuolated histiocytes, or in the form of foreign-body granulomas in surrounding fibroadipose tissue but not in capsules associated with smooth-walled implants. In 87 percent of samples of pericapsular tissue from textured saline implants, the contact surface displayed exuberant reactive synovial metaplasia, a histologic pattern not previously described with these devices. Our findings suggest that smooth-walled prostheses are associated with less silicone fragmentation than textured devices in the peri-implant tissue capsules that tend to form around artificial surfaces used for this purpose.

Breast↗
PubMed1993

Systemic inflammatory disorder related to fibrous breast capsules after silicone implant removal.

Silicone breast implants have been associated with connective-tissue inflammatory syndromes such as systemic sclerosis, and as with other artificial breast prostheses, fibrous capsules tend to form around the implants. The capsular tissue is generally considered inert and typically is left in situ when the prostheses are explanted. We report a patient who formed symptomatic bilateral submammary cysts associated with pain, swelling, arthralgia, fever, axillary lymphadenopathy, accelerated erythrocyte sedimentation rate, and antinuclear antibody following removal of intact silicone breast implants without capsulectomy. Clinical improvement followed removal of the capsules, which histologically displayed fragments of silicone, fibrous tissue, and inflammatory cells. Our experience suggests that when silicone breast implants are thought to be the cause of a clinical inflammatory syndrome characterized by mammary pain, swelling, arthralgia, or serologic abnormalities, consideration should be given to removing the capsules entirely so that the chance of a perpetuating reaction will be reduced.

Arthritis↗
PubMed1992

Carcinosarcoma of the submandibular salivary gland. Immunohistochemical findings.

Carcinosarcomas of the salivary glands are rare lesions that generally have been associated with benign mixed tumors. The authors report a case of a submandibular gland lesion, which occurred in a 64-year-old man, that was composed of intermingled ductal type adenocarcinoma and osteogenic sarcoma with a large component of osteoclast-like giant cells. The local recurrence of the tumor was entirely sarcomatous with no epithelial component observed. There was no histologic evidence of a preexisting or coexisting pleomorphic adenoma. Immunohistochemical studies confirmed two separate populations of tumor cells, corresponding to the histologic growth pattern. The authors review the literature and discuss histogenetic implications of distinction between de novo carcinosarcoma and carcinosarcoma in association with pleomorphic adenoma.

Carcinoma, Intraductal, Noninfiltrating↗
PubMed1992

Primary endobronchial actinomycosis in association with foreign body aspiration.

A 66-year-old diabetic man presented with a bilobar pneumonia two months after aspiration of a chicken bone. Flexible fiberoptic bronchoscopy demonstrated a mass in the bronchus intermedius. Histologic examination of endobronchial biopsy specimens revealed bone fragments, vegetable matter, and sulfur granules containing Actinomyces organisms. The patient responded to bronchoscopic removal of the foreign body and penicillin therapy. To our knowledge, the association of actinomycotic infection with an aspirated endobronchial foreign body has not previously been reported.

Actinomycosis↗