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L Ottestad

Publications and source records attributed to L Ottestad.

At least 19 recordsLinked to original sources
PubMed2001

Influence of neoadjuvant anastrozole (Arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer.

Anastrozole (Arimidex) is a novel, selective, and potent aromatase inhibitor used for the treatment of postmenopausal breast cancer. The drug has been shown to inhibit in vivo aromatization by 96--97% and to suppress plasma estrogen levels by 84--94%. However, the effects of anastrozole on intratumoral estrogen levels have not been studied. Here we report the effects of neoadjuvant treatment with anastrozole on intratumoral levels of estrone (E(1)), estradiol (E(2)), and estrone sulfate (E(1)S), measured by a highly sensitive RIA following a multistep purification procedure involving high-pressure liquid chromatography. Tumor tissue was obtained prior to treatment and after 15 weeks on therapy with anastrozole (1 mg once daily) from 12 postmenopausal women with locally advanced breast cancer (T(3)--T(4) and/or N(2)). Pretreatment tissue levels of E(2), E(1), and E(1)S were 217.9 (69.8--679.9), 173.6 (83.9--358.9), and 80.7 (31.4--207.3) fmol/g tissue (geometric mean values with 95% confidence interval, respectively). Treatment with anastrozole suppressed tissue E(2), E(1), and E(1)S levels by 89.0% (73.2--95.5%), 83.4% (63.2--92.5%), and 72.9% (47.3--86.1%), respectively, compared with baseline levels, with no significant difference between responders and nonresponders. Plasma levels of E(2), E(1), and E(1)S were suppressed by 86.1, 83.9, and 94.2%, respectively. Anastrozole caused a decrease in the immunoexpression of the proliferation markers Ki67 and pS2 in all of the patients, with a trend for a more profound suppression in those achieving an objective response. The mean percentage of apoptotic cells was found to be decreased in responders and increased in nonresponders after 15 weeks of anastrozole therapy. Our results reveal anastrozole to cause a significant suppression of tissue estrogen levels and to influence the biology of primary estrogen receptor-positive breast cancers in postmenopausal women.

Aged↗
PubMed1997

Loss of heterozygosity at 11q23.1 in breast carcinomas: indication for involvement of a gene distal and close to ATM.

Previous reports have suggested that heterozygotes for ataxia-telangiectasia (A-T) have an increased risk of cancer, in particular breast cancer. The ATM gene, responsible for A-T, was recently cloned. Loss of heterozygosity (LOH) in the chromosome band 11q23, where the ATM gene is located, has been reported in several types of tumours including breast carcinomas. Whether the ATM gene is the target, and the sole target, for the LOH seen in this region is not yet known. In this study, 169 primary breast carcinomas and 10 metastases were examined for allelic imbalance (AI) using 10 microsatellite markers mapping to 11q23.1. Nine of the markers reside within a 10 Mb region surrounding the ATM gene, whereas the tenth locus, APOC-3, is located more than 12 Mb telomeric from this region. The highest frequencies of alteration were found for APOC-3 (45%), and for two markers located approximately 200 and 900 kb telomeric from ATM, D11S1294 (44%) and D11S1818 (44%). The marker located within the ATM gene, D11S2179, was altered in 37% of the informative tumours. The present deletion map indicates that three distinct regions at 11q23.1 may be involved in breast cancer development; one between the markers D11S1294 and D11S1818, a second close to APOC-3, and a third that is possibly the ATM-gene itself.

Adult↗
PubMed1996

Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer.

The effect of anastrozole ('Arimidex', ZD1033), a new, selective, non-steroidal aromatase inhibitor on in vivo aromatisation and plasma oestrogen levels was evaluated in post-menopausal women with breast cancer. Twelve patients progressing after treatment with tamoxifen were randomised to receive anastrozole 1 mg or 10 mg once daily for a 28 day period in a double-blinded crossover design. In vivo aromatisation and plasma oestrogen levels were determined before commencing treatment and at the end of each 4-week period. Treatment with anastrozole 1 and 10 mg reduced the percentage aromatisation from 2.25% to 0.074% and 0.043% (mean suppression of 96.7% and 98.1% from baseline) and suppressed plasma levels of oestrone, oestradiol and oestrone sulphate by > or = 86.5%, > or = 83.5% and > or = 93.5% respectively, irrespective of dose. Notably, several patients had their oestrone and oestradiol values suppressed beneath the sensitivity limit of the assays. In conclusion, anastrozole was found to be highly effective in inhibiting in vivo aromatisation with no difference in efficacy between the two drug doses. Contrary to previous studies on other aromatase inhibitors, this study revealed an internal consistency between the percentage aromatase inhibition and suppression of plasma oestrone sulphate.

Anastrozole↗
PubMed1995

[Chemotherapy-induced hemolytic uremic syndrome. A complication to mitomycin treatment of breast carcinoma].

Mitomycin is a cytotoxic antibiotic that was first introduced into clinical use in 1958. Not until twenty years later was it recognised that haemolytic uremic syndrome could develop after treatment with mitomycin. It can be asked whether this condition was undiagnosed in previous years, since its frequency is now reported to be 4-15%. The disease appears to be dose-related, since it rarely occurs in patients who have received mitomycin < 30 mg/m2. No effective therapy has been established. We describe two patients with breast cancer in remission after treatment with mitomycin in combination with 5-fluorouracil. Both developed haemolytic uremic syndrome with fatal outcome.

Adult↗
PubMed1993

Flow cytometric DNA analysis as prognostic factor in human breast carcinoma.

Fresh tumour tissue from 198 primary invasive breast carcinomas was analysed by DNA flow cytometry. 108 tumours were non-diploid. A significantly higher proportion of non-diploid tumours was found among node-positive patients, patients with oestrogen receptor negative tumours and among patients with ductal carcinomas. The survival of patients with diploid and non-diploid tumours was not significantly different (p = 0.1). Totally, 145 tumours were analyzed with respect to S-phase fraction (SPF). The distribution of SPF was different in diploid and non-diploid tumours. A low SPF group, defined as the lower SPF quartile (< or = 4.6% in diploid and < or = 8.5% in non-diploid tumours), was associated with highly differentiated tumours and oestrogen receptor positive tumours. Histological grading revealed a highly significant correlation to SPF. 57% of ductal carcinomas grade I (8 out of 14), 30% of ductal carcinomas grade II (20 out of 67) and 5% of ductal carcinomas grade III (2 out of 37) had a low SPF. Patients within the low SPF group had a significantly longer survival than had patients within the high SPF group (p = 0.006). In a multivariate analysis the SPF was found to be an additional prognostic factor next to node status and ER status.

Aged↗
PubMed1993

Prognostic significance of TP53 alterations in breast carcinoma.

Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival.

Adult↗
PubMed1993

Amplification of c-erbB-2, int-2 and c-myc genes in node-negative breast carcinomas. Relationship to prognosis.

Primary tumours from 100 Norwegian node-negative breast carcinoma patients were examined for c-erbB-2, int-2, and c-myc proto-oncogene amplification. c-erbB-2, int-2, and c-myc amplification was found in 12.1% (12 of 99), 8.6% (8 of 93), and 1.1% (1 of 89) of the samples respectively. All the c-erbB-2 amplified tumours were of the ductal type, and all the int-2 amplified tumours were oestrogen receptor positive. No other significant or borderline significant associations between gene amplification and clinical or histopathological parameters were found. Relapse occurred more frequently in patients with c-erbB-2 gene amplification (relapse in 33.3% of the patients with c-erbB-2 amplification compared to 20.7% in the non-amplified group), but the difference was not statistically significant, int-2 amplification was not associated with increased risk of relapse, whereas the prognostic value of the c-myc amplification could not be evaluated.

Adult↗
PubMed1992

Screening for germ line TP53 mutations in breast cancer patients.

The constant denaturant gel electrophoresis technique was used to screen for TP53 germ line mutations in 237 women with breast carcinoma (167 unselected patients, 30 patients with at least one first-degree relative with breast cancer, and 40 women diagnosed with breast cancer before age 35). A germ line mutation at codon 181 was noted in one of the unselected patients and a codon 245 mutation in one of the early-onset patients. Both had a family history of breast cancer and other malignancies suggestive of Li-Fraumeni syndrome. The codon 245 mutation was also present in this patient's affected mother.

Adult↗
PubMed1992

Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas.

Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.

Adult↗
PubMed1990

The effect of pre-morbid height and weight on the survival of breast cancer patients.

A total of 8,427 women with breast cancer with height and weight measured prior to the diagnosis were followed up for on average 4.3 years. 2,383 women died from breast cancer and 430 from other causes. Among women diagnosed without any metastasis (stage I) the death rate was 1.70 times higher for those belonging to the highest quintile of body mass with respect to age compared to those in the lowest quintile. For patients with involved lymph nodes at diagnosis (stage II) the death rate was 1.42 times higher. Overweight was not a prognostic factor for stages III and IV patients. The prognostic effect of body mass in stages I and II was mainly connected to those in the highest quintile and was found for women in pre- as well as post-menopausal age. The effect did not depend on the length of time between measurement and diagnosis. Height was not found to be of prognostic relevance. The idea of the feasibility of a dietary trial in terms of the minimum trial size is given.

Body Height↗
PubMed1990

Amplification and protein over-expression of the neu/HER-2/c-erbB-2 protooncogene in human breast carcinomas: relationship to loss of gene sequences on chromosome 17, family history and prognosis.

c-erbB-2 gene amplification and protein over-expression were investigated in 89 primary tumours and 24 metastases from Norwegian breast cancer patients. Amplification occurred in 22.5% of the primary tumours and 50% of the metastases. The amplification was negatively correlated to the oestrogen receptor (ER) content in both the primary tumours and the metastases. No significant differences between amplified and non-amplified tumours were observed with regard to node status, clinical stage, tumour size or menopausal status, although correlations of borderline significance were found between node status, clinical stage and high degree of gene amplification. All the amplified tumours were of the invasive ductal type. Follow-up data of patients observed for more than 1 year showed a significantly higher recurrence rate in the c-erbB-2 amplified group. Allele loss of chromosome 17p and of 7q was seen in 55% and 48% of the tumours respectively. No significant correlation was found between these losses and clinico-histological parameters. More than 50% of the tumours with a loss of 17q sequences had an amplification of c-erbB-2 which is located on 17q12-21, indicating that only one of the chromosomes may be involved in the amplification of the c-erbB-2. A trend towards a correlation between loss of 17q and high degree of amplification were found. No correlation was found between positive family history of breast cancer and c-erbB-2 gene amplification, nor loss of 17p or 17q sequences. Our data support the hypothesis that amplification correlates with aggressive tumour behaviour, and thus may be used as a prognostic factor in breast carcinomas. The allele losses on 17p and 17q points to tumour suppressor gene or genes on this chromosome, although not as predisposing genes in families.

Breast Neoplasms↗
PubMed1990

Drug sensitivity testing of human breast cancer.

A survey of drug sensitivity testing of human breast cancer is given. The purpose of sensitivity testing, the tumour material studied, and the various in vivo and in vitro assays that are being used are discussed. Moreover, examples of results obtained are presented.

Animals↗
PubMed1989

Colony forming ability of human breast carcinomas: lack of prognostic significance.

To study whether colony growth in vitro reflects the prognosis of breast cancer patients, specimens from a total number of 138 patients with primary breast carcinomas were cultivated in the Courtenay-Mills soft agar method. The plating efficiency (PE) values were related to various clinical and histopathological parameters. No significant correlation was found between colony forming ability and menopausal status, histopathology, TNM-status or steroid hormone receptor status. The crude survival of the patients was not significantly correlated to the in vitro growth of the tumours; neither was there any difference in relapse-free survival between patients whose tumours failed to grow in vitro and those having growing tumours (PE greater than 0). A multivariate survival analysis of 115 patients with primary tumours without distant metastases revealed that the PE was not a significant independent prognostic indicator, as it gave no additional prognostic information above that of node and ER status. It is concluded that routine measurement of colony formation in vitro is not warranted in the management of breast cancer.

Adult↗
PubMed1988

Cultivation of human breast carcinoma in soft agar. Experience with 237 fresh tumour specimens.

A total of 237 breast carcinomas have been studied with the Courtenay-Mills (C-M) soft agar method. Cell yields and plating efficiencies (PE) were recorded after various enzyme treatments. The highest cell yields and PEs were obtained with the combination of collagenase 0.5%, hyaluronidase 1000 IE ml-1 and DNase 0.1% and an incubation time of 2 h. Eighty percent of the specimens gave greater than 10 colonies, and 60% formed greater than 30 colonies permitting chemosensitivity studies. The C-M method gave significantly higher PEs than the Hamburger-Salmon (H-S) method. Hormone supplements (insulin, oestradiol, progesterone, hydrocortisone) and also reduced agar concentrations (less than 0.3%) gave marginal stimulation of colony formation. In chemosensitivity studies involving doxorubicin, vincristine and 4-OOH-cyclophosphamide, the C-M method gave dose-response relationships without plateaus.

Breast Neoplasms↗
PubMed1988

Neuroendocrine activity in metastatic breast carcinomas.

The expression of NSE and hormone immunoreactivity were examined in lymph node metastases from 15 primary breast carcinomas (6 NSE-positive and 9 NSE-negative). NSE immunoreactivity was expressed in metastases in 7 cases. Both the primary tumour and lymph node metastasis(es) were NSE-positive in 3 cases. In 4 cases NSE-negative primary tumours were associated with NSE-positive lymph node metastases. In 2 of the 7 cases with NSE-positive metastases, the metastatic lesions did not express uniform NSE immunoreactivity. Immunoreactivity for hormones (gastrin (1 case), prealbumin (2 cases), ACTH and beta-endorphin (1 case) and somatostatin (1 case] was present in 5 of the 7 NSE-positive lymph node metastatic lesions. In one case only the same hormone (gastrin) was expressed in both the primary tumour and its lymph node metastasis. The present study shows that no relationship exists between primary tumours and the corresponding lymph node metastases with regard to NSE and hormone immunoreactivity.

Adrenocorticotropic Hormone↗