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S Gundersen

Publications and source records attributed to S Gundersen.

At least 19 recordsLinked to original sources
PubMed2000

The prognostic value of p53 and c-erb B-2 immunostaining is overrated for patients with lymph node negative breast carcinoma: a multivariate analysis of prognostic factors in 613 patients with a follow-up of 14-30 years.

BACKGROUND: Approximately 30% of breast carcinoma patients with negative lymph nodes die of their disease. Biologic markers such p53 protein and c-erb B-2 have been related to tumor progression, but their prognostic value remains controversial. METHODS: Two large series of a total of 613 lymph node negative breast carcinoma patients from a single institution were analyzed with respect to tumor size, histologic grade, and immunohistochemical staining for p53, c-erb B-2, estrogen receptor (ER), and progesterone receptor (PgR). Interobserver variation in histologic grading was evaluated by Kappa statistics. The two series had different treatment modalities: 228 patients (SACGS group) were treated surgically with mastectomy and given 1 perioperative chemotherapy course, and 385 patients (HOST group) were treated with mastectomy and ovarian radiation and further randomized to receive postoperative treatment with radiotherapy or no adjuvant treatment. The follow-up ranged from 14-30 years. RESULTS: Immunoreactivities for p53, c-erb B-2, ER, and PgR did not differ significantly in the two series. p53 immunostaining was present in 187 of 613 tumors (29%), and c-erb B-2 immunoreactivity was present in 58 of the tumors (10%). Three hundred forty-eight tumors (57%) were positive for ER. Kappa statistics value of interobserver variation in the histologic grading of ductal carcinomas was 0.69, which is considered to be a substantial degree of agreement. No significant differences in survival were found when comparing p53, c-erb B-2, ER, and PgR positive and negative cases. However, both recurrence free survival rates and overall survival rates after 10 years were significantly better in the T1N0M0 group compared with the T2N0M0 group (81% vs. 67% [P < 0.0001] and 85% vs. 70% [P < 0.0001]). Ten-year recurrence free survival rates for patients with histologic Grade 1 versus Grades 2-3 (according to Elston and Ellis' modification of the Bloom and Richardson method) tumors were 90% and 70%, respectively (P < 0. 0001), and overall survival rates for the same groups were 94% and 81%, respectively (P=0.0002). After 30 years of follow-up, the overall survival rate for patients with tumors of histologic Grade 1 versus Grades 2-3 were 87% and 68%, respectively, and were 78% and 66%, respectively, for patients with tumors </= 2 mm versus those with tumors > 20-50 mm. Approximately 35% of the patients with tumors of histologic Grades 2-3 and measuring > 20 mm were dead after 10 years of follow-up, contrary to 6% of the patients with tumors of histologic Grade 1 measuring </= 20 mm. A significantly more favorable prognosis also was observed in patients in the HOST group treated with adjuvant radiotherapy. CONCLUSIONS: Histologic grade and tumor size were found to be major prognostic factors for patients after 30 years of follow-up. c-erb B-2 and p53 immunostaining does not appear have any independent prognostic value. Adjuvant radiotherapy may be of value in the treatment of patients with localized tumors.

Adult↗
PubMed1998

A retrospective study of the value of chemotherapy as adjuvant therapy to surgery and radiotherapy in grade 3 and 4 gliomas.

The aim of this retrospective study was to evaluate the effect of adjuvant chemotherapy among patients < 55 years of age with anaplastic gliomas (historical grade 3, n = 85) with four cycles 4 weeks apart of 160 mg carmustine (BCNU) infused into the internal carotid artery, combined with vincristine 2 mg and procarbazine 50 mg x 3 for 1 week (i.a.BCNU-PV) versus no adjuvant chemotherapy. In glioblastomas (histological grade 4, n = 257) the same chemotherapy was evaluated versus two cycles 4 weeks apart of 160 mg lomustine (CCNU) orally instead of BCNU, combined with vincristine and procarbazine (PCV) versus no chemotherapy. All patients in both groups received radiotherapy. Among glioblastoma patients < 55 years of age there was a significant (P = 0.03), but moderately increased survival in the i.a.BCNU-PV group versus the two other arms that did not differ from each other. This difference could be explained by an uneven distribution of prognostic factors, especially age group (< 50 years versus 50-54 years) in favour of the i.a.BCNU-PV group. In anaplastic gliomas, the median survival in the i.a.BCNU-PV group was 80 months versus 25 months for the no chemotherapy arm (P = 0.004). No significant differences in the distribution of prognostic factors were found between the two therapy arms. We suggest that the role of adjuvant chemotherapy in glioblastomas is unclear, while i.a.BCNU-PV as adjuvant chemotherapy among patients < 55 years of age and with anaplastic gliomas increased survival markedly.

Administration, Oral↗
PubMed1998

Influence of droloxifene on metastatic breast cancer as first-line endocrine treatment.

The effect of droloxifene (3-hydroxytamoxifen) given as first-line endocrine treatment was evaluated in 39 postmenopausal women with advanced receptor-positive or receptor-unknown breast cancer. The patients had not received any previous anticancer therapy apart from adjuvant treatment. The overall response rate (CR + PR) was 51% (8% CR, 43% PR), 95% confidence interval+/-15.7%. Median time to progression (all patients) was 8 months, the median time to response 2 months, while the median duration of response was 10 months. The drug was well tolerated with no major side effects recorded; 16% of the patients experienced hot flushes. The response to droloxifene recorded in the present study is in accordance with the response rates to tamoxifen as first-line treatment in identical groups of patients.

Aged↗
PubMed1997

[Check up of breast cancer stages 1 and 2].

We have studied the efficacy of investigations during follow-up of 430 operable node positive and node negative breast cancer patients. Median follow-up was eight years, and 128 patients had relapsed, 91 with metastatic disease. Eight blood analyses, chest X-ray, limited skeletal X-ray and bone scan examinations were undertaken at regular intervals. Of the patients who had relapsed, 59% had symptoms, 23% were detected by clinical examination and 18% were detected by blood analysis only. X-rays and scintigrams were of little value in proportion to the costs. The combination of three blood analyses was useful. An increase in sedimentation rate (ESR) of more than 10 mm/h, an increase in gamma-glutamyltransferase (GT) of 20 U/l and an increase in alkaline phosphatase (ALP) of 60 U/l or more. By using ESR, gamma-GT, ALP, history and clinical examination, costs could be reduced by 90% while maintaining adequate baseline screening for relapse.

Breast Neoplasms↗
PubMed1997

Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study.

The study was planned to compare, in a prospective double-blind randomized trial, the efficacy and safety of toremifene (TOR) and tamoxifen (TAM) in post-menopausal patients with advanced breast cancer who have not had prior systemic therapy for advanced disease. Four hundred and fifteen post-menopausal patients with oestrogen receptor (ER)-positive or ER-unknown advanced breast cancer were randomly assigned to receive daily either 60 mg TOR or 40 mg TAM. The patients were stratified to measurable and non-measurable but evaluable groups. They were assessed for response to therapy, time to progression (TTP), time to treatment failure (TTF), response duration, overall survival and drug toxicity. Two hundred and fourteen patients were randomized into TOR and 201 into TAM treatment. The response rate (complete + partial) was 31.3% for TOR and 37.3% for TAM (P = 0.215). The 95% confidence interval (CI) for the 6% difference was -15.1% to 3.1%. The median TTP was 7.3 months for TOR and 10.2 months for TAM (P = 0.047). The 95% CI for the hazard ratio of 0.80 was 0.64-1.00. A percentage of the TOR patients (9.8%) and the TAM patients (18.9%) discontinued the treatment prematurely (P = 0.011) for various reasons. Consequently, the median TTF of 6.3 vs 8.5 months did not differ significantly (P = 0.271). The hazard ratio was 0.89 and the subsequent 95% CI 0.73-1.09. The median overall survival was 33.0 months for TOR and 38.7 months for TAM (P = 0.645). The hazard ratio was 0.94 with 95% CI of 0.73-1.22. The transient difference in TTP may be related to an imbalance in ER content of the tumours. When only patients with ER-positive tumours were considered (n = 238), no difference between two treatments was seen (P = 0.578). TAM was associated with an overall slightly higher frequency of adverse drug reactions than TOR (44.3 vs 39.3%) and a higher discontinuation rate due to these events (3.5% vs 0.9%). Treatment-emerged moderate dizziness (P = 0.026) and cataracts (P = 0.026) were more frequent among TAM than among TOR patients. In conclusion, TOR (60 mg day(-1)) and TAM (40 mg day(-1)) are equally effective and safe in the treatment of advanced post-menopausal ER-positive or ER-unknown breast cancer.

Adult↗
PubMed1996

[Prognosis in primary tumors of the central nervous system. A patient material from the Norwegian Radium Hospital 1960-94].

We present the results of a retrospective survey of 1,218 patients treated at the Norwegian Radium Hospital during the years 1980-94 for primary tumours of the central nervous system. Median survival for patients with glioblastoma (n = 492) was 12 months, for patients with anaplastic astrocytoma (n = 83) 25 months, astrocytoma (n = 260) 95 months, oligodendroglioma (n = 85) 74 months, mixed glioma (n = 68) 65 months, and medulloblastoma (n = 53) 109 months. Median survival for patients with brain stem tumours (n = 37) was nine months, while 74% of patients with tumours in the pineal region (n = 38) survived for five years. The histology and localisation of the tumour, as well as age and functional status, are important prognostic factors for survival in patients with primary CNS tumours.

Adolescent↗
PubMed1996

[Tumor size and histological grading of stage 1 breast cancer. Prognostic and therapeutic significance].

Systemic adjuvant therapy can improve the prognosis for breast cancer patients. In node negative disease most patients have a good prognosis with local therapy only. Therefore, identification of subgroups with higher risk of relapse is warranted in order to avoid overtreatment of a large number of patients. A total of 399 tumours from patients without axillary metastases, operated on in the years 1964-72, were measured preoperatively and graded according to a modified Scharff-Bloom-Richardson scheme. Patients with T2 (UICC) tumours and histologic grade 2 and 3, had a 3.3-fold relative risk of mortality from breast cancer compared with the rest of the patients. These patients should receive adjuvant systemic therapy.

Aged↗
PubMed1996

Prognostic factors for glioblastoma multiforme--development of a prognostic index.

The prognosis for glioblastoma multiforme is generally poor. However, it can be useful to identify groups of patients with varying prognosis. Based on data from 495 consecutive patients admitted to the Norwegian Radium Hospital during 1980-1994, multivariable methods were used to identify prognostic factors independently associated with length of survival. A prognostic index was derived in 384 randomly selected patients, and tested in 111 other patients. Performance status, dexamethasone dependency, age group, surgery and behavioural changes were prognostic discriminators. On this basis a prognostic index was made and three separate subsets with different survival prognoses could be identified. The prognostic index was then tested among 20% of the patients and shown to predict reliable survival curves. In the subset with the highest index (high risk subset) almost all patients in the main group as well as in the the test group were dead within 18 months.

Age Factors↗
PubMed1996

Circulating anodic antigen (CAA) levels in different age groups in a Zimbabwean rural community endemic for Schistosoma haematobium determined using the magnetic beads antigen-capture enzyme-linked immunoassay.

A simplified version of the magnetic bead antigen-capture enzyme-linked immunoassay (MBAC-EIA) was used to detect circulating anodic antigen (CAA) in individuals of different age groups with Schistosoma haematobium infection only in an endemic area of Zimbabwe. An overall positive correlation between S. haematobium egg excretion and CAA levels was demonstrated. The age profile for CAA levels was generally comparable with the age profile of S. haematobium prevalence and intensity of infection. The CAA levels were higher in younger (5-14 years of age) individuals than in older (greater than 14 years of age) ones. Since the sensitivity of the MBAC-EIA in the diagnosis of S. haematobium infection was found to be 97%, CAA levels appear to be a useful indicator of worm burden in an endemic area.

Adolescent↗
PubMed1995

Adjuvant tamoxifen for pre- and postmenopausal women with estrogen receptor positive, node positive breast cancer: a randomized study.

370 patients with operable, axillary node positive breast cancer, were randomized to receive tamoxifen (TAM) 20 mg/day for 2 years or no adjuvant hormone therapy. All patients had estrogen receptor (ER) positive (ER > 10 pmol/g) primary tumours. 350 patients, 93 younger than 50 years of age and 257 patients 50 years or older, were evaluable for the study. After a median follow up of 76 months, significantly (p = 0.0001) fewer loco-regional, but not distant (systemic), relapses have been recorded in the TAM group. Overall survival was also improved, but even though the study was designed to give maximum benefit from TAM statistically significant effect of TAM seemed to be limited to patients 50 years of age and older.

Antineoplastic Agents, Hormonal↗
PubMed1995

Influence of treatment with the anti-oestrogen 3-hydroxytamoxifen (droloxifene) on plasma sex hormone levels in postmenopausal patients with breast cancer.

Plasma levels of oestradiol (Oe2), oestrone (Oe1) oestrone sulphate (Oe1S), androstenedione, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG) and the gonadotrophins (FSH and LH) were determined in 20 postmenopausal women with breast cancer treated with the anti-oestrogen droloxifene (3-hydroxytamoxifen). Plasma oestrogens were measured before and after 3, 6 and 12 months of therapy. The other hormones were measured before and after 6 months of therapy. Droloxifene treatment had no significant influence on plasma levels of Oe2. Plasma levels of Oe1 and Oe1S increased during treatment (mean increase of 11.9-15.9% and 24.5-69.4% respectively after different time-intervals on treatment). The Oe1S/Oe1 and Oe1S/Oe2 ratios increased by mean values of 13.8-45.2% and 25.9-52.4% respectively. Plasma SHBG increased significantly by a mean value of 73.9%, while FSH and LH fell non-significantly by 19.7% and 20.4% respectively. Plasma levels of testosterone, androstenedione, DHEA and DHEAS all increased during treatment, but none of these alterations were of statistical significance. While the influence of droloxifene on plasma SHBG resembled that which is seen during treatment with tamoxifen, its influence on plasma oestrogens and the gonadotrophins seems to be different. Possible explanations of such differences and the clinical implications of alterations in plasma hormones during treatment with droloxifene are discussed.

Aged↗
PubMed1994

Weekly doxorubicin with or without high-dose medroxyprogesterone acetate in hormone-resistant advanced breast cancer. A randomised study. The Norwegian Breast Cancer Group.

In a randomised study, 218 patients with advanced breast cancer, resistant to hormone therapy, received either doxorubicin 20 mg every week (Awkly) alone or Awkly combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 210 evaluable patients, the response rates were 26% [95% confidence interval (CI) 18-34%] for Awkly and 38% (95% CI 29-47%) for Awkly + HD-MPA (P = 0.08). There was no significant difference with regard to duration of response. Median survival was 11 months in both groups. Considerable toxicity was seen from HD-MPA, particularly weight gain and fluid retention. The present study provides evidence that, in concordance with preclinical studies and a previous randomised study, interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. For further studies, other gestagens and/or a dose reduction could be investigated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Follow-up of breast cancer patients stage I-II: a baseline strategy.

In 430 stage I-II breast cancer patients the cost-benefit of investigations during follow-up have been studied. Median follow-up time was 8 years and 128 patients had relapsed, 91 with metastatic disease. High costs of routine chest X-ray, limited skeletal X-ray and bone scan examinations were associated with low incidence of diagnosed relapses not suspected otherwise. In the eight blood analyses examined, increases of more than 10 mm/h in erythrocyte sedimentation rate (ESR), 20 U/l in gamma-glutamyltransferase (GT) or 60 U/l in alkaline phosphatase (ALP) resulted in a combined sensitivity of 55% and specificity of 91% for relapses with distant metastases. Elevation of at least two blood tests gave a combined sensitivity of 31% and a specificity of 98%. The importance of using individual reference values in screening for recurrences is emphasised. Symptomatic relapse or relapse detected at interval visits were not independent prognostic factors. The blood tests ALP, ESR and GT were strong predictors of survival measured from relapse which increase their legitimacy in follow-up. A more frequent follow-up for patients with 4+ involved nodes is proposed: three visits annually the first 5 years vs. two visits annually for the others. We conclude that history, clinical examination, ALP, ESR and GT are sufficient as a baseline screening for relapse in breast cancer patients.

Aftercare↗
PubMed1993

Randomized phase II trial of iproplatin and carboplatin in advanced breast cancer. The EORTC Early Clinical Trials Group and the EORTC Data Center.

BACKGROUND: The observed activity of cisplatin in breast cancer and its unattractive toxicity profile in palliative treatment warranted further study of platinum analogues in this disease. PATIENTS AND METHODS: Sixty-two patients with recurrent or metastatic breast cancer, 61 of whom had been previously treated with chemotherapy, were randomly assigned to therapy with either iproplatin (n = 32) or carboplatin (n = 30). Both platinum analogues were administered intravenously, iproplatin at a dose of 240 mg/m2 every 4 weeks and carboplatin at a dose of 450 mg/m2 every 5 weeks. RESULTS: Only two patients responded to iproplatin (7%) for durations of 21 and 61 weeks, and one patient responded to carboplatin (3%) for a duration of 64 weeks. All responses were complete. At the given dose schedules carboplatin was more myelosuppressive than iproplatin. Non-hematologic toxicities included nausea and vomiting (93% vs. 90%), diarrhea (20% vs. 10%) and hemorrhage (16% vs. 10%) for iproplatin and carboplatin, respectively. Two patients developed alopecia with carboplatin. No renal toxicity was observed. CONCLUSIONS: Both iproplatin and carboplatin have limited activity in previously treated women with advanced breast cancer when given in conventional dosages.

Adult↗
PubMed1992

[Prognostic parameters in localized breast cancer].

About 8% of women in Norway will develop breast cancer. 55% of these will have a node negative disease. The current debate concerns whether all women in stage I should be treated with adjuvant therapies. In this article we discuss different prognostic factors with the objective of subdividing node negative breast cancer patients into different prognostic groups. Risk factors include age under 30 years and over 70 years, increasing size of tumour, a high histological grade and negative oestrogen receptor status. We believe that, in future, evaluation of ploidy, proliferation antigens, oncogenes and possibly cathepsin D will be useful in selecting breast cancer patients in stage I for adjuvant therapy.

Adult↗