Search PubMed⌕ Search

Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 37 records · Page 2Linked to original sources
PubMed2002

Local recurrence in the breast after conservative surgery--a study of prognosis and prognostic factors in 391 women.

In a population-based cohort of 6613 women with invasive breast cancer, who had breast-conserving surgery between 1981 and 1990, 391 recurrences in the operated breast were identified. The main aim of this study was to examine the prognosis and prognostic factors in different subgroups of local recurrences, characterised by the time to recurrence, location of recurrence and previously given radiotherapy. The median follow-up for women who had a local recurrence was 7.9 years. The life-table estimates for breast cancer-specific survival in women with local recurrences were 84.5% (standard error (S.E.) 1.8) at 5 years and 70.9% (S.E. 2.7) at 10 years. The risk of breast cancer death was highest among women who had an early (<or=2 years) recurrence in the same quadrant as the primary tumour, with a breast cancer-specific survival of 67.9% (S.E. 4.8) at 5 years and 56.0% (S.E. 5.9) at 10 years. There was a statistically significant difference in the probability of breast cancer-specific survival, as measured from the recurrence, between women who initially did or did not receive radiotherapy (P=0.0123). However, when measured from primary treatment, there was no significant difference, indicating that the difference in prognosis could be due to a lead-time bias. Independent prognostic factors for breast cancer-specific survival in women with local recurrences were time to local recurrence and the Nottingham Prognostic Index (NPI).

Adult↗
PubMed2002

Ductal carcinoma in situ of the breast: a new phenotype classification system and its relation to prognosis.

In a study of invasive breast cancer, multiple correspondence analysis (MCA) revealed clustering of eight pathobiological variables. Two different phenotypes were distinguished by an index calculated on the basis of the variables (histologic grade, necrosis, lymphoid infiltration, number of mitosis and expression of c-erbB-2, p53, progesterone receptor and Bcl-2). Phenotype A lesions share most of the features of normal breast tissue. Phenotype B looks more malignant, has a higher early recurrence rate and is more frequently seen in younger patients. Our aim was to see if ductal breast carcinoma in situ (DCIS) could be divided into the same phenotypes. One hundred and eighty DCIS were investigated. Association between the eight variables was studied in 2 x 2 models. The phenotype index was calculated by summing weights for the variables in the MCA. All variables were associated, except Bcl-2. DCIS was divided in two phenotypes. Thirty-three tumours were Phenotype A and 147 Phenotype B. The mean age at diagnosis was 65.5 and 58.4 years for Phenotypes A and B, respectively (p = 0.0012). No difference regarding local relapse free survival was seen. Two phenotypes were distinguished in DCIS, similar to invasive breast cancer. In an earlier study, 45% of the invasive cancers were classified as Phenotype B. In this study, 82% of DCIS were Phenotype B. This may indicate that invasive breast cancer of Phenotype B is derived from DCIS of Phenotype B. The distribution of DCIS phenotypes with a small proportion of Phenotype A DCIS may be due to that Phenotype A DCIS is less likely to be detected by mammography, or that some invasive breast cancers of Phenotype A progress to invasiveness without passing the in situ phase.

Adult↗
PubMed2002

Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study.

Blockade of tumor necrosis factor (TNF)alpha by a soluble TNF receptor fusion protein (etanercept; Enbrel) improved in vitro hemopoiesis from the marrow of patients with myelodysplastic syndrome (MDS). Therefore, we enrolled 14 MDS patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot trial. Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to three times a week if no response at 8 weeks). Among 12 evaluable patients, four had rises in hemoglobin by 1-1.5 gm/dl (three) or decreased transfusion requirements (one). Two patients had increased platelet counts (54% and 73%), and two increased neutrophils (63% and 120%). Baseline TNFalpha levels, determined in all patients, did not correlate with responses. Among eight marrows available for sequential in vitro assays, four showed increases in CFU-GM of 1.5- to 5-fold at 8 weeks, whereas three showed 3- to 10-fold decrements relative to baseline. Thus, etanercept treatment resulted in moderate improvements of cytopenias in some patients, while cell counts declined in others. Additional trials are needed to evaluate its clinical efficacy in MDS.

Adult↗
PubMed2002

Consequences of axillary recurrence after conservative breast surgery.

BACKGROUND: The aim was to study the incidence, time course and prognosis of patients who developed axillary recurrence after breast-conserving surgery, and to evaluate possible risk factors for axillary recurrence and prognostic factors after axillary recurrence. METHODS: In a population-based cohort of 6613 women with invasive breast cancer who had breast-conserving surgery between 1981 and 1990, 92 recurrences in the ipsilateral axilla were identified. Risk factors for axillary recurrence were studied in a case-control study nested in the cohort, and late survival was documented in the women with axillary recurrence. RESULTS: The overall risk of axillary recurrence was 1.0 per cent at 5 years and 1.7 per cent at 10 years. The risk of axillary recurrence increased with tumour size (P = 0.033) and was highest in younger women (odds ratio (OR) 3.9 for women aged less than 40 years compared with those aged 50-59 years). Radiotherapy to the breast reduced the risk of axillary recurrence (OR 0.1 (95 per cent confidence interval 0.1 to 0.4)). The breast cancer-specific survival rate after axillary recurrence, as measured from primary treatment, was 78.0 per cent at 5 years and 52.3 per cent at 10 years. Tumour size and node status had a statistically significant effect on death from breast cancer. CONCLUSION: Axillary recurrence is rare, although more common in younger women with large tumours. Radiotherapy to the breast was protective. Tumour size and node status were the most important prognostic factors in women with axillary recurrence.

Adult↗
PubMed2002

Five-node biopsy of the axilla: an alternative to axillary dissection of levels I-II in operable breast cancer.

BACKGROUND: Axillary clearance of patients with early breast cancer is accompanied by a high risk of arm morbidity. Less invasive ways to establish the axillary nodal status are therefore of interest, especially in women with low risk of nodal metastases. METHODS: Four hundred and fifteen breast cancer patients (clinical stage T(0-3) N(0-1) M(0)) were operated in the axilla with a five-node biopsy followed in the same operation by a further dissection of levels I-II of the axilla in order to evaluate the accuracy of the five-node node biopsy compared with level I-II dissection. RESULTS: In all patients the sensitivity of the five-node biopsy was 97.3% with a negative predictive value of 98.5% and a negative likelihood ratio of 0.027. Among cases detected by screening (n=204) and those clinically detected (n=197) the sensitivity of the five-node biopsy was 95.8% and 97.9% respectively, with negative predictive values of 98.7% and 98.0% and negative likelihood ratios of 0.042 and 0.021 respectively. CONCLUSION: Five-node biopsy of the axilla has good accuracy for correctly staging the axilla in both clinically and screening-detected cases. Five-node biopsy is an alternative to axillary clearance and sentinel node biopsy in patients with operable breast cancer.

Aged↗
PubMed2002

Compliance and findings in a Swedish population screened for colorectal cancer with sigmoidoscopy.

AIM: The aim of this study was to evaluate the patterns of compliance and the frequency of adenomas and neoplasms in a Swedish population. METHODS: In 1996, 2000 men and women born in 1935 or 1936 were selected at random from the population registers of Uppsala and Malmö/Lund. All subjects were invited by mail to participate. In a randomised study design, subjects were either called up by a nurse to schedule the appointment for sigmoidoscopy or instructed to call themselves. At sigmoidoscopy subjects with a cancer, an adenoma (neoplastic polyp) or more than three hyperplastic polyps were scheduled for a complete colonoscopy. RESULTS: Thirty-nine percent (770/1988) of all the invited subjects had a sigmoidoscopy. The participation differed between the two centres, 47% at the Uppsala centre and 30% at the Malmö/Lund centre (P<0.01). There was no statistically significant difference between the two different invitation groups. In all, 98 subjects (13%) were planned for colonoscopy. Thirty-one (35%) of the subjects having a colonoscopy were women and 57 (65%) were men. Fifty-five true adenomas were found in 46 subjects. All together, six subjects had proximal adenomas. Five adenocarcinomas were diagnosed, all within the reach of the sigmoidoscope. CONCLUSIONS: The compliance was lower and the adenomas were fewer than expected. To increase compliance it is necessary with rigorously controlled invitation routines.

Adenoma↗
PubMed2002

Areas of concern, quality of life and life satisfaction in patients with peripheral vascular disease.

OBJECTIVES: to explore the ways in which peripheral vascular disease subjectively affect patients and to relate these findings to validated measurements of quality of life (QOL) and life satisfaction. DESIGN: a cross-sectional study. SUBJECTS: eighty patients, with carotid artery stenosis (CAS), abdominal aortic aneurysm (AAA), intermittent claudication (IC) or critical limb ischaemia (CLI). METHODS: semi-structured interviews were used to explore the effect of the disease on the patients life situation. QOL was assessed by SF-36 and life satisfaction by LiSat-11. RESULTS: the SF36, LiSat-11 and our interview revealed two principal patterns: one for patients with CAS and AAA, and one for patients with IC and CLI. The interview revealed important areas affecting the vascular patient. Some of these areas: higher intellectual function, concern, sexual function, family concern and factors related to the operated areas were not covered by either the SF36 or the LiSat-11. CONCLUSIONS: for a full understanding of how peripheral vascular disease affects the individual, disease specific questions need to be added to generic QOL instruments and measurements of life satisfaction.

Adult↗
PubMed2002

Prostate-specific antigen for prostate cancer staging in a population-based register.

OBJECTIVE: Previous studies have shown a relationship between serum prostate-specific antigen (PSA) level and prostate tumour volume. Reports based on selected case series have also indicated that serum PSA may be used for staging, although a varying prevalence of metastasizing tumours complicates the interpretation of these studies. In order to determine the accuracy of the serum level of PSA in predicting the presence of metastases we performed a prospective cohort study of a geographically defined population of men with prostate cancer. METHODS: Serum level of PSA and the results of investigations for regional lymph node and distant metastases were recorded for all 8328 men with prostate cancer registered in the Swedish National Prostate Cancer Register 1996-1997. RESULTS: The prevalence of lymph node metastases among men who had undergone lymph node exploration was 4%, 16% and 33% for well, moderately and poorly differentiated tumours. The corresponding prevalence of distant metastases was 12%, 30% and 48%. With serum PSA <20 ng/ml as a cut-off point the negative likelihood ratios for well and moderately differentiated tumours were found to be 0.47 and 0.45 for lymph node metastases and 0.24 and 0.18 for distant metastases, resulting in post-test probabilities >92% for the exclusion of metastases. In men with poorly differentiated tumours, the negative likelihood ratio would need to be even lower to safely exclude disseminated disease. CONCLUSION: For well to moderately differentiated tumours, further investigations to assess the presence of metastases may be omitted with no great risk for understaging if serum PSA <20 ng/ml.

Aged↗
PubMed2002

Prostate-specific antigen as surrogate for characterizing prostate cancer subgroups.

OBJECTIVE: To evaluate how serum prostate-specific antigen (PSA) levels in a population-based cohort of men with prostate cancer vary with age and intensity in the diagnostic activity and to describe the treatment selection processes associated with PSA level. MATERIAL AND METHODS: All men in the Swedish National Prostate Cancer Register diagnosed during 1996-1997 were included. In 1996 the register included 19 counties, covering 61% of the Swedish male population, and in 1997 21 counties with 79% of the Swedish male population. RESULTS: A total of 8328 men were registered. PSA levels were missing in 341 cases. With increasing PSA there was a shift towards more advanced and poorly differentiated tumours. PSA at diagnosis increased with age, with the exception of patients younger than 50 years who had higher PSA values. The mean logarithm of PSA correlated negatively with the percentage of localized tumours (p < 0.005) and the age-adjusted incidence (p < 0.05) in each respective county in 1997. PSA was higher in men receiving radiotherapy compared with those treated with radical prostatectomy as well as in the group treated with bilateral orchiectomy compared with those receiving GnRH-analogues. CONCLUSIONS: If PSA is used as a surrogate measure of extent of tumour volume in a population of prostate cancer patients, our findings indicate that age distribution and differences in incidence (possibly due to variation in diagnostic activity) should be taken into account. In our cohort there was a selection process, probably in part guided by PSA level, when choosing type of curative or palliative treatment.

Age Factors↗
PubMed2002

Health, health-compromising behaviour, sexuality and involvement in pregnancy among 18-year-old Swedish males: a cross-sectional survey.

UNLABELLED: The aim of this study was to determine whether there are differences regarding well-being, health habits and health-compromising behaviour between Swedish young men who had never had sexual intercourse (group I), those who were sexually active but without a pregnancy record (group II), and those who had caused pregnancies (group III). A self-report questionnaire was used covering questions regarding health, health habits and risk behaviour. Tests of significance for differences between the three groups were performed with chi 2-tests. Differences were found in health, health behaviour and risk-taking behaviour between the three groups of young men, with an apparent tendency towards riskier lifestyles from group I, through group II, to group III. Two especially striking findings were the more frequent use of anabolic steroids and the reported high rate of sexual offences in group III compared with groups I and II. CONCLUSION: This study highlights serious health-compromising behaviours in 18-y-old men involved in pregnancies in a medium-sized Swedish city. This group has been largely ignored both in clinical practice and in scientific studies, in contrast to the huge efforts directed towards pregnant adolescent females. Public health workers, school health programmes and adolescent clinics need to acknowledge this and work accordingly.

Adolescent↗
PubMed2001

Increased p53 mutation frequency during tumor progression--results from a breast cancer cohort.

The mutational patterns of the p53 gene for exons 4-9 were analyzed in 30 recurring tumors compared with the p53 status of the corresponding 30 primary breast cancers. The prevalence of p53 mutations was higher, although not statistically significant (P = 0.07), in the evaluable recurring tumors compared with the corresponding primaries, 12 of 29 (41%) versus 7 of 30 (23%). Twenty-one of the patients had unchanged p53 mutation status in the recurring compared with the primary tumors, whereas 8 had an altered mutational status or pattern in the sequential tumor. These findings indicate that p53 mutations may be an important factor for tumor progression in human breast cancer.

Breast Neoplasms↗
PubMed2001

Tumour markers in breast carcinoma correlate with grade rather than with invasiveness.

Ductal breast carcinoma in situ (DCIS) is regarded as a precursor to invasive breast cancer. The progression from in situ to invasive cancer is however little understood. We compared some tumour markers in invasive and in situ breast carcinomas trying to find steps in this progression. We designed a semi-experimental setting and compared histopathological grading and tumour marker expression in pure DCIS (n = 194), small invasive lesions (n = 127) and lesions with both an invasive and in situ component (n = 305). Grading was done according to the Elston-Ellis and EORTC classification systems, respectively. Immunohistochemical staining was conducted for p53, c-erbB-2, Ki-67, ER, PR, bcl-2 and angiogenesis. All markers correlated with grade rather than with invasiveness. No marker was clearly associated with the progression from in situ to invasiveness. The expression of tumour markers was almost identical in the 2 components of mixed lesions. DCIS as a group showed a more 'malignant picture' than invasive cancer according to the markers, probably, due to a higher proportion of poorly differentiated lesions. The step between in situ and invasive cancer seems to occur independently of tumour grade. The results suggest that well-differentiated DCIS progress to well-differentiated invasive cancer and poorly differentiated DCIS progress to poorly differentiated invasive cancer.

Biomarkers, Tumor↗
PubMed2001

Myeloablation and autologous peripheral blood stem cell rescue results in hematologic and clinical responses in patients with myeloid metaplasia with myelofibrosis.

Current therapeutic options for myeloid metaplasia with myelofibrosis (MMM) are limited. A pilot study was conducted of autologous peripheral blood stem cell (PBSC) collection in 27, followed by transplantation in 21 patients with MMM. The median age was 59 (range 45-75) years. PBSCs were mobilized at steady state (n = 2), after granulocyte colony-stimulating factor (G-CSF) alone (n = 17), or after anthracycline-cytarabine induction plus G-CSF (n = 8). A median of 11.6 x 10(6) (range 0 to 410 x 10(6)) CD34(+) cells per kilogram were collected. Twenty-one patients then underwent myeloablation with oral busulfan (16 mg/kg) and PBSC transplantation. The median times to neutrophil and platelet recovery after transplantation were 21 (range 10-96) and 21 (range, 13 to > or = 246) days, respectively. Five patients received back-up PBSC infusion because of delayed neutrophil or platelet recovery. The median follow-up is 390 (range 70-1623) days after transplantation, and the 2-year actuarial survival is 61%. After transplantion, 6 patients died: 3 of nonrelapse causes (1 within 100 days of PBSC infusion) and 3 of disease progression. Erythroid response (hemoglobin > or = 100 g/L [10 gm/dL] without transfusion for > or = 8 weeks) occurred in 10 of 17 anemic patients. Four of 8 patients with a platelet count less than 100 x 10(9)/L (100 000/microL) responded with a durable platelet count more than 100 x 10(9)/L (100 000/microL). Symptomatic splenomegaly improved in 7 of 10 patients. It is concluded that (1) PBSC collection was feasible and stable engraftment occurred after transplantation in most patients with MMM, (2) myeloablation with busulfan was associated with acceptable toxicity, (3) a significant proportion of patients derived clinical benefit after treatment, and (4) further investigation of this novel approach is warranted. (Blood. 2001;98:586-593)

Aged↗
PubMed2001

Fruit, vegetables, dietary fiber, and risk of colorectal cancer.

BACKGROUND: Several recent large prospective cohort studies have failed to demonstrate the presumed protective effect of fruit, vegetable, and dietary fiber consumption on colorectal cancer risk. To further explore this issue, we have examined these associations in a population that consumes relatively low amounts of fruit and vegetables and high amounts of cereals. METHODS: We examined data obtained from a food-frequency questionnaire used in a population-based prospective mammography screening study of women in central Sweden. Women with colorectal cancer diagnosed through December 31, 1998, were identified by linkage to regional cancer registries. Cox proportional hazards models were used to estimate relative risks. All statistical tests were two-sided. RESULTS: During an average 9.6 years of follow-up of 61 463 women, we observed 460 incident cases of colorectal cancer (291 colon cancers, 159 rectal cancers, and 10 cancers at both sites). In the entire study population, total fruit and vegetable consumption was inversely associated with colorectal cancer risk. Subanalyses showed that this association was due largely to fruit consumption. The association was stronger, however, and the dose-response effect was more evident among individuals who consumed the lowest amounts of fruit and vegetables. Individuals who consumed less than 1.5 servings of fruit and vegetables per day had a relative risk for developing colorectal cancer of 1.65 (95% confidence interval = 1.23 to 2.20; P(trend) =.001) compared with individuals who consumed more than 2.5 servings. We observed no association between colorectal cancer risk and the consumption of cereal fiber, even at amounts substantially greater than previously examined, or of non-cereal fiber. CONCLUSIONS: Individuals who consume very low amounts of fruit and vegetables have the greatest risk of colorectal cancer. Relatively high consumption of cereal fiber does not appear to lower the risk of colorectal cancer.

Colorectal Neoplasms↗
PubMed2001

The expression of vascular endothelial growth factor correlates with mutant p53 and poor prognosis in human breast cancer.

Wild-type p53 protein has been shown to inhibit angiogenesis through thrombospondin in the preclinical setting. Here, we determined the associations between the expression of the angiogenic factor vascular endothelial growth factor (VEGF) and the p53 status, including different mutation sites and types, in primary breast cancer. Cytosols from 224 primary breast cancer patients were analyzed with an enzyme immunoassay for determination of human VEGF165 protein content. p53 status was determined by cDNA-based sequencing of the entire coding region, by immunohistochemistry (IHC), and by a p53 luminometric immunoassay (LIA) method. Statistically significant associations was found between higher VEGF content and non-wild-type p53 status for all methods; sequence-based data (P = 0.0019), IHC data (P = 0.0068), and the LIA method (r = 0.427; P > 0.001). Highest VEGF values were detected in tumors with p53 insertions, deletions, and stop codon mutations (P = 0.0043). Combining p53 status and VEGF content resulted in additional prognostic information, relapse-free survival (RFS; P = 0.0377), overall survival (OS; P = 0.0319), and breast cancer corrected survival (BCCS; P = 0.0292). In multivariate analysis, the relative hazard increased when the VEGF data were added to the p53 status, with a relative hazard of 1.7 for RFS and 3.0 for BCCS, compared with 1.1 for RFS and 1.4 for BCCS among the patients with either high VEGF content or p53 mutation. Higher VEGF content was statistically significantly correlated with a worse outcome for patients with estrogen receptor-positive tumors receiving adjuvant tamoxifen: RFS (P = 0.0471), OS (P = 0.0134), BCCS (P = 0.0064), as well as in multivariate analysis with point estimates of 3.4 and 2.1 for BCCS and RFS, respectively. VEGF expression is related to p53 status in human breast cancer patients. Combining VEGF with p53 status resulted in better prognostic prediction.

Adult↗
PubMed2001

Dietary antioxidant vitamins, retinol, and breast cancer incidence in a cohort of Swedish women.

Dietary antioxidant vitamins and retinol have been proposed to be protective against breast cancer on the basis of their ability to reduce oxidative DNA damage and their role in cell differentiation. Epidemiologic studies have not been convincing in supporting this hypothesis, but women with high exposure to free radicals and oxidative processes have not been specifically considered. We explored these issues in the Swedish Mammography Screening Cohort, a large population-based prospective cohort study in Sweden that comprised 59,036 women, 40-76 years of age, who were free of cancer at baseline and who had answered a validated 67-item food frequency questionnaire. During 508,267 person-years of follow-up, 1,271 cases of invasive breast cancer were diagnosed. Cox proportional hazards models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). There was no overall association between intake of ascorbic acid, beta-carotene, retinol or vitamin E and breast cancer incidence. High intake of ascorbic acid was inversely related to breast cancer incidence among overweight women (HR=0.61; 95% CI 0.45-0.82, for highest quintile of intake among women with body mass index>25 kg/m(2)) and women with high consumption of linoleic acid (HR=0.72; 95% CI 0.52-1.02, for highest quintile of ascorbic acid intake and average consumption of more than 6 grams of linoleic acid per day). Among women with a body mass index of 25 or below, the hazard ratio for breast cancer incidence was 1.27 (95% CI 0.99-1.63), comparing the highest to the lowest quintile of ascorbic acid intake. Consumption of foods high in ascorbic acid may convey protection from breast cancer among women who are overweight and/or have a high intake of linoleic acid.

Adult↗