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J Bergh

Publications and source records attributed to J Bergh.

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

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

Induction of p53 expression in skin by radiotherapy and UV radiation: a randomized study.

BACKGROUND: p53 protein plays an important role in the response to DNA damage, and radiotherapy can cause radiation dermatitis. p53 and p21 levels increase in vitro when DNA is damaged by UVA, UVB, or gamma-radiation. To determine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin exposed to different types of radiation as part of a randomized study of women with breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast. METHODS: After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 women were irradiated with UVA and other areas were irradiated with UVB. Skin biopsy samples were taken from areas of normal unirradiated skin and all irradiated areas, and p53 and p21 were detected immunohistochemically. All statistical tests are two-sided. RESULTS: In skin irradiated with UVA or UVB, medians of 4.4% (range = 0%-40.5%) or 45.5% (range = 5.3%-74.6%) p53-positive keratinocytes, respectively, were observed. Radiotherapy produced medians of 31.0% (range = 0%-79.3%) p53-immunoreactive cells after 2 Gy of radiation and 83.2% (range = 37.6%-95.2%) after 54 Gy of radiation. Despite large interindividual differences in p53 response, comparable increases in epidermal p53 response were independent of the type of radiation. A correlation between p53 and p21 was also evident (r(s) =.78). In breast skin, there was no association between the p53 response and the degree of erythema (a measure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses. CONCLUSIONS: Individual responses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the degree of radiation dermatitis.

Aged↗
PubMed2001

Potent corticosteroid cream (mometasone furoate) significantly reduces acute radiation dermatitis: results from a double-blind, randomized study.

PURPOSE: Radiation-induced dermatitis is a very common side effect of radiation therapy, and may necessitate interruption of the therapy. There is a substantial lack of evidence-based treatments for this condition. The aim of this study was to investigate the effect of mometasone furoate cream (MMF) on radiation dermatitis in a prospective, double-blind, randomized study. MATERIAL AND METHODS: The study comprised 49 patients with node-negative breast cancer. They were operated on with sector resection and scheduled for postoperative radiotherapy using photons with identical radiation qualities and dosage to the breast parenchyma. The patients were randomized to receive either MMF or emollient cream. The cream was applied on the irradiated skin twice a week from the start of radiotherapy until the 12th fraction (24 Gy) and thereafter once daily until 3 weeks after completion of radiation. Both groups additionally received non-blinded emollient cream daily. The intensity of the acute radiation dermatitis was evaluated on a weekly basis regarding erythema and pigmentation, using a reflectance spectrophotometer together with visual scoring of the skin reactions. RESULTS: MMF in combination with emollient cream treatment significantly decreased acute radiation dermatitis (P=0.0033) compared with emollient cream alone. There was no significant difference in pigmentation between the two groups. CONCLUSIONS: Adding MMF, a potent topical corticosteroid, to an emollient cream is statistically significantly more effective than emollient cream alone in reducing acute radiation dermatitis.

Acute Disease↗
PubMed2001

Short- and long-term anxiety and depression in women recalled after breast cancer screening.

The aim was to investigate the psychological consequences of further investigation after breast cancer screening. Study participants include 509 women (61%) recalled due to suspicious findings on screening mammograms, and a matched control group of 285 women (68%) with normal mammograms. Psychological distress was prospectively assessed with the Hospital Anxiety and Depression Scale (HADS). 46% of the women reported borderline or clinically significant anxiety prior to the recall visit. A few days after the visit, anxiety and depression had decreased significantly (P<0.01) in women informed about normal or benign results at the recall clinic, while reported distress remained at relatively high levels in women referred to surgical biopsy. The results demonstrate the adverse short-term effect of a delay in receiving false-positive results, but do not indicate that the recall experience results in long-term anxiety or depression for a majority of women.

Adult↗
PubMed2001

Effects of dose-intensive chemotherapy and radiotherapy on serum n-terminal proatrial natriuretic peptide in high-risk breast cancer patients.

By using N-terminal proatrial natriuretic peptide (proANP) in serum as a marker of cardiac function, we compared the cardiac side effects of two intensive adjuvant treatment regimens for breast cancer. Patients received either 9 cycles of FEC (5-fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (n = 49, FEC-group) or three cycles of FEC followed by high-dose chemotherapy with alkylating agents (n = 56, CTCb-group) given with the support of peripheral blood stem cells support. Both groups received adjuvant radiotherapy. Serial measurements of proANP were performed up to three years after treatment. Mean proANP values in the FEC-group was on average 19% higher than in the CTCb-group (p = 0.002). The proANP levels showed a significant association with the cumulative dose of epirubicin (p < 0.001) but not with cyclophosphamide (p = 0.151) and 5-FU (p = 0.160). The pharmacokinetics of epirubicin was studied at the first and third chemotherapy course. The proANP levels after treatment were significantly related to the AUC (p = 0.034) and Cmax(p = 0.037) of epirubicin. Left-sided chest irradiation was associated with on average 12% higher proANP values than right-sided (p = 0.031). We conclude that dose-escalated FEC causes a stronger increase in proANP than 3 FEC followed by high-dose CTCb-treatment. Increase of proANP levels might represent an early sign of cardiotoxicity secondary to chemotherapy and radiation treatment. Long-time follow-up is necessary to determine the clinical significance of these findings.

Adult↗
PubMed2001

Timing of quality of life (QoL) assessments as a source of error in oncological trials.

AIM OF THE STUDY: To produce an empirical estimate of the nature and magnitude of the error produced by incorrect timing quality of life (QoL) measurements in patients receiving chemotherapy. DESIGN: In a multicentre trial, 283 patients were randomized to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). The QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The study design was retrospective. Data were analysed using t-tests. RESULTS: Erroneous timing affected the QoL findings in both treatment arms. At baseline, there were statistically significant differences in the MF group on the nausea/vomiting scale, with ill-timed assessment showing more symptoms, and in the T group on the physical functioning scale with ill-timed assessments indicating better QoL. The mean scores of correct vs. incorrect timings over the first 14 cycles showed statistically significant differences on several scales. In the MF group, ill-timed assessments indicated significantly worse physical functioning and global QoL, and significantly more of the following symptoms: fatigue, nausea/vomiting, insomnia, appetite loss, and constipation. In the T group, ill-timed assessment showed better physical functioning, less dyspnoea and more insomnia than correctly timed assessments. The reasons for erroneous timing were not always detectable retrospectively. However, in some cases the MF group, being in standard treatment, seemed to have followed a clinical routine not involving the active participation of the study nurse responsible, whereas patients in the experimental T group were more consistently taken care of by the study nurses. CONCLUSIONS: Incorrect timing of QoL assessments in oncological trials jeopardises both the reliability of the QoL findings within treatment and the validity of QoL outcome comparisons between treatments. This issue should be emphasized in the planning of both the study design and clinical routines.

Activities of Daily Living↗
PubMed2001

Early response of breast cancer bone metastases to chemotherapy evaluated with MR imaging.

PURPOSE: To compare T1-weighted spin-echo and fat-suppressed long echo time inversion recovery turbo spin-echo (long TE IR-TSE) MR images in the evaluation of early response of breast cancer bone metastases to chemotherapy. MATERIAL AND METHODS: Eighteen breast cancer patients with known bone metastases were investigated prospectively by MR, using T1-weighted and long TE IR-TSE sequences on the sternum, spine, pelvis and proximal femora, before and after a median of 6 courses of chemotherapy. Therapeutic response evaluation with MR was based on change in tumor size assessed quantitatively by measuring all focal metastases, and change in pattern and signal intensity (SI) of the metastases, assessed visually. Combined response evaluation based on clinical findings, conventional radiography, and scintigraphy was used as reference. RESULTS: Progressive disease (2 patients) and no change (4 patients) were assessed equally well on both MR sequences. Long TE IR-TSE demonstrated partial response with higher accuracy than T1-weighted images, 58% (7/12 patients) vs. 17% (2/12 patients). In patients without progression there was an SI increase in or around the metastases in 6 patients on T1-weighted images and in 7 patients on long TE IR-TSE images. CONCLUSION: The long TE IR-TSE sequence demonstrated early partial response of breast cancer bone metastases to chemotherapy more accurately than the T1-weighted sequence.

Adult↗
PubMed2001

The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of chemotherapy effects in some major tumour types--summary and conclusions.

This report by The Swedish Council on Technology Assessment in Health Care (SBU) reviews, classifies, and grades the scientific literature on cancer chemotherapy in some major tumour types, describes the practice of chemotherapy in Sweden, compares practice with scientific knowledge, and analyses the costs and cost-effectiveness of chemotherapy. The report is intended primarily for decision-makers at various levels, both practitioners and administrators. It is also of interest for the medical profession. The extensive body of scientific literature was reviewed according to strict criteria that reflected the scientific weight of the literature. Sixteen experts representing different disciplines (oncology, surgery, internal medicine, health economy and quality of life research) participated in the literature review. Each section was discussed within the project group and was reviewed by at least one, but usually two international researchers. Additional input was provided by national experts representing different scientific disciplines. For the final evaluation to be as close to the objective truth as possible, a concerted effort was made to guarantee objectivity and thorough assessment of current knowledge about the effects of chemotherapy on the selected cancers. The tumour types selected for this assessment include firstly those types where three investigations had shown an increased use of chemotherapy in Sweden during the latest decade. These were non-small cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, colorectal cancer and urinary bladder cancer. Secondly, the two tumour types comprising the greatest number of patients treated with chemotherapy in Sweden, breast cancer and haematological malignancies, were included. Among the haematological malignancies, the most prevalent ones, acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), Hodgkin's disease (HD), aggressive non-Hodgkin's lymphoma (NHL) of the large B-cell type and indolent NHL of follicular type were evaluated. These constitute about 75%, of all haematological malignancies. Thirdly, ovarian cancer was included since chemotherapy has been extensively used and since, at the time of the planning of this overview, a group of very expensive drugs, the taxanes, had preliminarily shown promising results. A wealth of scientific literature has been published on cancer therapy. The review presented in this report is limited to scientific studies judged to be important for evaluating chemotherapy efficacy. Assessments of the content and quality of these studies, and a critical summary of the results in all stages of the selected tumours, have never before been attempted in this way. However, similar comprehensive overviews of certain stages of the tumours have previously been made. These overviews were also critically evaluated. Totally 1,496 studies involving 558,743 patients were reviewed. The survey of practice of chemotherapy use involved all departments of surgery, urology, gynaecology, internal medicine including haematologic units, pulmonary medicine and general and gynaecologic oncology at 16 hospitals in two health care regions in Sweden, covering 39% of the Swedish population. During the 4 weeks of the survey, all patients with the diagnoses concerned who received chemotherapy were registered. The study included 1,590 patients. The working group's general conclusions are summarised in the following points: The literature on the effects of chemotherapy is extensive. Chemotherapy has a well-documented role in the curative and palliative treatment of patients with several types of cancer. The use of chemotherapy is of utmost importance for the possibility of cure in certain tumour types. In other tumours, chemotherapy increases the possibility of cure when added to local and regional treatments, particularly surgery. In the instances of no possibility of cure, chemotherapy may to a variable extent improve both patient survival and well-being. In Sweden chemotherapy is largely used in accordance with that documented in the scientific literature. The extent of both over- and under-treatment seems to be limited but cannot be excluded at the individual patient level. The literature-based knowledge is scientifically of lower quality in the most chemotherapy sensitive tumours than in tumours showing more limited sensitivity. In the more sensitive tumours, positive effects on a symptomatic stage and survival were seen several decades ago. In those days, clinical treatment studies did not fulfil the current high quality requirements. Small life-prolonging effects of chemotherapy are sometimes very well documented in large, high quality scientific studies. Some of these s

Antineoplastic Agents↗
PubMed2001

A systematic overview of chemotherapy effects in breast cancer.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for breast cancer is based on 233 randomised studies, 9 meta-analysis of randomised studies, a population-based cohort study and 18 overviews/retrospective analyses including a total of 155,243 patients. The conclusions reached can be summarised into the following points: Adjuvant treatment-- There is solid scientific support from randomised studies that adjuvant polychemotherapy at 10 years will result in an absolute mortality reduction for patients younger than 50 years by 12% for node positive (34% relative mortality reduction corresponding to an estimated median survival prolongation of several years) and 6% for node negative patients. For women aged 50 to 69 years, the corresponding figures for node positive and node negative patients are 6% and 2%, respectively (approximately 11% relative mortality reduction). Anthracycline-containing combinations result in an absolute survival benefit at five years of 3%, compared with non-anthracycline based polychemotherapy. There are indications that the taxane paclitaxel may further improve the survival compared with anthracyclines. However, the limited data preclude conclusions for the routine care. The addition of tamoxifen to chemotherapy further enhances the survival benefit for receptor positive subgroups. The roles of more dose-intensive regimens, including high-dose therapy with stem cell support, are presently studied in randomised investigations. The data presented so far are conflicting but they do not in general support high-dose therapy. Quality of life, based on analyses of randomised studies, demonstrate that adjuvant polychemotherapy has an initial detrimental effect, but long-term follow-up of treated patients demonstrates no impairment of quality of life compared with untreated patients. Polychemotherapy in standard doses should be offered to premenopausal node positive patients, and the corresponding postmenopausal group with a receptor-negative breast cancer and to node negative patients with high risk factors. Polychemotherapy should be combined with tamoxifen to all patients with receptor-positive tumours. Due to a need of more knowledge in this field, patients should be included in investigational protocols. Locally advanced breast cancer-- Based on current knowledge, treatment of patients with locally advanced breast cancer should include neoadjuvant/preoperative polychemotherapy since there is evidence from controlled studies that such therapy will statistically significantly increase the number of patients who can be offered breast-conserving surgery. Indirect comparisons also demonstrate survival improvements, but the scientific support is equivocal. Metastatic breast cancer-- The median survival for patients with metastatic disease treated with conventional chemotherapy doses and regimens is 12 to 24 months. Retrospective cohort studies indicate that the use of non-anthracycline containing chemotherapy compared with no chemotherapy might add a survival gain of six to nine months. However, this estimation is based on equivocal data. Based on overview data, polychemotherapy results in a statistically significant survival gain compared with single-agent therapy. Based on repeated randomised studies, the addition of anthracyclines increases the response rate and statistically significantly improves the survival compared with non-anthracycline containing chemotherapy, except for CMF combined with prednisone/prednisolone, which will statistically significantly improve the survival compared with some anthracycline combinations. Second line therapy using vinorelbine or docetaxel is statistically significantly better than other regimens with a time to progression and survival benefit in the order of one to three months based on few randomised studies. The role, if any, of third line therapy is yet to be demonstrated. In the metastatic setting, conventional chemotherapy improves the quality of life. In standard care, first line therapy should contain an anthracycline and second line therapy using vinorelbine or docetaxel could be offered to selected patients failing first line therapy. Based on numerous randomised studies, breast cancer demonstrates a positive dose-response relationship both in the adjuvant situation and for metastatic disease. However, in the conventional dose-range there seems to be a plateau in the dose-response curve, with no further survival gains for high

Adult↗
PubMed2001

Who should not receive adjuvant chemotherapy? International databases.

The optimal selection of patients for adjuvant therapy, avoiding overtreatment and undertreatment, of disease is a significant challenge in the management of early breast cancers. Population-based cohorts in Denmark and in two Swedish health care regions were investigated to identify patients with breast cancer who have a sufficiently low risk of recurrence without adjuvant therapy. Published data on different calcification patterns were also included from the randomized Swedish mammography two-county study. The Danish Breast Cancer Group's population-based registry revealed that patients with lymph node-negative and estrogen receptor- or progesterone receptor-positive cancers of histological grade I that were less than 20 mm in size had a 5-year survival rate similar to age-matched groups without breast cancer. Data from the Stockholm Breast Cancer Group identified a similar risk group (no information on cancer grade) with an approximate 10% risk of dying from breast cancer after 10 years without any adjuvant therapy. In women older than 50 years, approximately 20% died of other causes. Mammographically and lymph node-negative-detected cancers that are less than 15 mm in size generally have an excellent survival outcome, excluding patients with casting calcifications. Patients who have lymph node-negative breast cancers that are less than 20 mm in size, combined with estrogen receptor positivity, can be identified as a low-risk group. The vast majority of these patients are unlikely to benefit from the addition of conventional chemotherapy, but some of them may. The dilemma is that we cannot identify these patients prospectively because of the lack of relevant predictive factors for chemotherapy.

Breast Neoplasms↗
PubMed2001

Effects of nutrition and soil water availability on water use in a Norway spruce stand.

We investigated effects of nutrition and soil water availability on sap flux density, transpiration per unit leaf area (EL), and canopy stomatal conductance (GS) of Norway spruce (Picea abies L. (Karst.)) in northern Sweden during the 1996 growing season. Our objectives were to determine (1) if artificially imposed drought (65% rain diversion) reduces soil water sufficiently to cause physiological limitations to whole-tree and plot-scale water transport, and (2) whether increased capacity for water transport resulting from fertilization-induced increases in leaf (> 3-fold) and sapwood areas (> 2.3-fold) deplete soil water sufficiently to cause a negative feedback on GS and EL. We monitored soil water content (theta) and soil water potential (PsiS) in control (C), drought (D), fertilized (F) and irrigated + fertilized (IL) treatment plots, along with site meteorological conditions. Ten trees per plot were monitored for sap flow. Although there were significant treatment differences in mean daily EL (C > D > F; P < 0.01) and GS (C > D > F; P < 0.05), variation in absolute magnitudes was small. Therefore, transpiration differences on a unit ground area basis (EC) were nearly proportional to leaf area differences. Precipitation was well distributed throughout the study period and so PsiS remained high, except during short dry periods in Plot F when it declined rapidly. Thus, although soil water was not limiting to GS, EL or EC when precipitation was uniformly distributed throughout the growing season, we cannot conclude that water availability would not limit GS in fertilized stands if the seasonal distribution of precipitation were altered.

Picea↗
PubMed2001

Enzymatic mutation detection method evaluated for detection of p53 mutations in cDNA from breast cancers.

BACKGROUND: Rapid, reproducible, and easily run methods with high sensitivity and specificity are required for mutation screening of clinical samples. We evaluated the Enzymatic Mutation Detection (EMD(TM)) method by analysis of archival cDNA from 203 breast cancer patients and comparison with results of cDNA-based sequencing of the tumor suppressor gene p53. METHODS: The EMD technology uses the T4 endonuclease VII, which cleaves double-stranded DNA at sites where a DNA mismatch is present because of mispairing or an insertion/deletion of nucleotides. The EMD analyses were carried out by dividing the p53 gene into two overlapping fragments that were analyzed separately. After PCR amplification, the fragments were hybridized with wild-type p53 and subsequently exposed to the EMD enzyme. Cleavage products were analyzed and scored using an ALF(TM) automated DNA sequencer and ALFwin Fragment Analyzer software (VER: 1.02). RESULTS: The EMD technique had sensitivities of 45% and 64% and specificities of 83% and 84% for the two fragments, respectively. Patients with EMD-positive, wild-type p53 tumors had a survival similar to that of patients with EMD-negative, wild-type p53 tumors. Node-positive patients with p53 mutated tumors according to sequencing had a statistically significantly worse overall survival than those with p53 wild-type tumors (P = 0.016), whereas this difference in survival was not detected when p53 status was determined with EMD (P = 0.47). CONCLUSIONS: EMD had insufficient sensitivity for consideration in screening for the p53 gene in this archival material. Sequencing must still be considered as the standard procedure.

Breast Neoplasms↗
PubMed2001

Risk factors for subsequent invasive breast cancer and breast cancer death after ductal carcinoma in situ: a population-based case-control study in Sweden.

In a case-control study derived from a cohort of 4661 women with a primary carcinoma in situ of the breast, we investigated age at diagnosis, mode of detection, tumor characteristics, and primary therapy, as prognostic factors for developing invasive breast cancer or dying from breast cancer. From all of the women with a primary carcinoma in situ reported to the Swedish Cancer Registry from 1960 through 1992, we selected as cases all of the women with a ductal carcinoma in situ who later died of breast cancer (n = 39) or who developed a subsequent invasive cancer in either breast (n = 118). From this cohort, we also selected controls matched to the cases by year of diagnosis and health care region. We conducted univariate and multivariate analyses to study the association between risk of invasive cancer or death and the different risk factors. Large size, diameter > or = 25 mm [odds ratio (OR), 3.5; 95% confidence interval (CI), 1.1-11.4] and multifocality (OR, 3.9; 95% CI, 1.2-12.7) increased the risk of breast cancer death in univariate analysis. Postoperative radiotherapy (OR, 0.1; 95% CI, 0.0-1.0) and mastectomy (OR, 0.1-95% CI, 0.0-0.5) lowered the risk of an ipsilateral invasive cancer in multivariate analysis. The risk pattern by treatment category differed between those who had an ipsilateral invasive cancer and those who either had a contralateral cancer or died from breast cancer. The driving forces behind local and generalized disease may differ. Because confounding by indication may influence the effects of different treatments, the results should be interpreted with caution.

Adult↗
PubMed2000

Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Scandinavian Breast Group 9401 study.

BACKGROUND: Chemotherapy drug distribution varies greatly among individual patients. Therefore, we developed an individualised fluorouracil, epirubicin, cyclophosphamide (FEC) regimen to improve outcomes in patients with high-risk early breast cancer. We then did a randomised trial to compare this individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. METHODS: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. FINDINGS: At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double triangular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experienced more grade 3 or 4 acute toxicity compared with the tailored FEC group (p<0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Six patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome. INTERPRETATION: Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.

Acute Disease↗