Timing of breast cancer surgery--some arguments that there is no effect.
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Breast Neoplasms↗
Biomedical subjects
W Sauerbrei
Publications and source records attributed to W Sauerbrei.
Randomized 2 x 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients. German Breast Cancer Study Group.
PURPOSE: In 1984, the German Breast Cancer Study Group (GBSG) started a multicenter randomized clinical trial to compare the effectiveness of three versus six cycles of 500 mg/m2 cyclophosphamide, 40 mg/m2 methotrexate, and 600 mg/m2 fluorouracil (CMF) on day 1 and 8 starting perioperatively with or without tamoxifen (TAM) (3 x 10 mg/d for 2 years). The aim of the trial was to compare recurrence-free and overall survival between the different treatment modalities. PATIENTS AND METHODS: During 5 years, 41 institutions randomized 473 patients (3 x CMF: 145; 3 x CMF + TAM: 93; 6 x CMF 144; 6 x CMF + TAM: 91). Until March 31, 1992, median follow-up time was 56 months with 197 events for disease-free survival and 116 deaths observed. This provides a power of approximately 80% to detect a potential treatment difference corresponding to a relative risk (RR) of 0.67 for recurrence-free survival. Treatment modalities and various patient characteristics were evaluated by means of a multivariate Cox regression analysis. RESULTS: No significant difference in recurrence-free survival was observed with respect to hormonal therapy (RR = 0.75 TAM v no TAM; 95% confidence interval [CI], 0.54 to 1.04; P = .08) as well as duration of chemotherapy (RR = 0.90 of 6 x CMF v 3 x CMF; 95% CI, 0.67 to 1.19; P = .45). Similar results were obtained for overall survival. The multivariate analysis revealed a significant prognostic impact of the number of positive lymph nodes and the progesterone receptor level on recurrence-free survival. Compliance with chemotherapy within the range of 85% to 115% of the target dose was achieved in 94% and 78% of the patients randomized to 3 x CMF and 6 x CMF, respectively. Sufficient compliance with TAM was reported for 141 patients (93%). CONCLUSION: At this stage of follow-up, six courses of CMF are not superior to three courses with respect to recurrence-free survival.
Adult↗
[Therapy of hypopharyngeal cancer. Part IV: Long-term results of transoral laser microsurgery of hypopharyngeal cancer].
Between 1979 and 1986, 74 patients with hypopharyngeal carcinomas were operated using transoral laser microsurgery by the first author. 32 of the patients were subdivided into 5 subgroups and considered separately because of pretreatment for head and neck tumors, simultaneous multiple tumors etc. (excluding criterias). Survival times were not significantly prolonged and lasted 1-27 months (median, 11 months), but the quality of life was improved due to preservation or restoration of natural laryngopharyngeal functions. Forty-two patients were operated with curative intention. This group primarily underwent transoral laser microsurgery, aiming at complete locoregional tumor resection with function preservation (pT1, 5; pT2, 31; pT3, 4; pT4, 2). In 29 patients 31 necks were operated, mostly as a regionally limited functional neck dissection (or "selective" neck dissection). In 90% of the cases neck metastases (pN+) were found, mostly in levels II and III; pN1, 6; pN2a, 1; pN2b, 18; pN2c, 1. Altogether, stages III and IV were found in 71.4% of the patients. A temporary tracheotomy was required in four patients. There was no secondary laryngectomy, even though it was indicated in one case. Post-treatment oncological followup (median observation time, 104 months) demonstrated loco-regional recurrences (n = 1), late or recurrent metastases (n = 4), persisting metastases in the neck with cerebral metastasis (n = 1), distant metastases (n = 4), secondary tumors (n = 9, 5 of which occurred in the head and neck). Through March 1993, 24 patients (57%) have died. Causes were TNM-related (7), second primary tumor with or without distant metastases (8) and intercurrent disease with no evidence of disease (9). Within 5 years 17% of the patients died of TNM-related tumors, 9.5% due to a second primary with or without distant metastases, as well as 9.5% with intercurrent disease. The 5-year overall survival rate was 64% and was 83% (adjusted survival rate) if only TNM-related deaths were considered.
Adult↗
Steroid receptors in carcinoma of the breast. Results of immunocytochemical and biochemical determination and their effects on short-term prognosis.
A group of 241 nonpretreated breast carcinomas was studied for estrogen receptor (ER) and progesterone receptor (PR) content by both immunocytochemistry (ICC) and biochemical analysis (dextran-coated charcoal [DCC]). While the tumors were judged to be ER positive in 67.6% and PR positive in 65.6% by ICC, DCC analysis showed positive results in 77.6% for both ER and PR. There was only a moderate correlation between the semiquantitative results of ER and PR ICC and the corresponding values for DCC receptor determination. Among tumors shown to be steroid receptor positive by ICC, a majority showed a wide spectrum of staining intensity, from negative to intensely positive (type C staining pattern, ER 87.7%, PR 73.4%). Less frequently, carcinomas showing uniform, intense staining of all epithelial tumor cells were observed (type A staining pattern, ER 11.7%, PR 18.4%). Finally, only very few tumors had both clearly negative and distinctly positive cells (type B staining pattern, ER 0.6%, PR 8.2%). On analyzing the relationship between the expression of steroid receptors (ICC and DCC) and the prognostic factors axillary node status, tumor size, tumor histology, grade and patient age, only a significant correlation between patient age and ER (ICC, r = .46; DCC, r = .43), a weakly significant negative correlation between node involvement and ER, and a weakly significant negative correlation between tumor grade and ER (ICC only) as well as between tumor grade and PR were found. Among all patients, the recurrence-free interval was significantly longer in patients with ER- or PR-positive carcinomas (ICC and DCC).(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Monoclonal↗
Influence of model-building strategies on the results of a case-control study.
We evaluate the analysis of a case-control study in which many variables were investigated simultaneously. The purpose of the study was to explore some rather unspecific hypotheses about potential risk factors for adult brain tumour. Our aim is to show that in the analysis of case-control studies many decisions are necessary which are usually not published in detail. As in most studies these decisions are made during analysis and are data dependent. We demonstrate that the data allow sensible alternative decisions which influence the final results. A sensitivity analysis of several aspects of the analysis such as different measurement scales, variable selection, handling of missing values and interactions was performed, and demonstrated variation in the results based on the strategy for analysis. We conclude that details of the final analysis should be decided in the planning phase of a case-control study, and that more details of model-building strategies must be published. Results from a study where the analysis is highly data dependent must be interpreted with caution and validation of the results with new studies is essential.
Bias↗
Preoperative staging of breast cancer by palpation, mammography and high-resolution ultrasound.
In breast cancer preoperative determination of the tumor size is important for planning breast-conserving operations. In 100 patients with breast cancer, the preoperative tumor size was measured using clinical, mammographic and sonographic examinations and correlated with the results of a subsequent histological examination. Using a high-resolution real-time system, 98 tumors were visible. It was possible to detect not only early tumors under 1 cm in diameter, but also intraductal tumor components. This contributed greatly to the accuracy of the diagnosis. The sonographic measurement of tumor size demonstrated a correlation coefficient of 0.91 and was thus superior to mammography (0.79) and palpation (0.77). Measurement of the total tumor spread, including 39 multicentric lesions, showed an overestimation of 5% for the mammographic measurements and an overestimation of 4% for the sonographic measurements. Tumor extension was underestimated in 33% of the mammograms but in only 3% using ultrasound examination. The results, along with those of other studies, highlight the role of sonography in the diagnosis of breast cancer.
Journal Article↗
The prognostic effect of histological tumor grade in node-negative breast cancer patients.
The prognostic effect of histological tumor grade was evaluated in 1036 patients with early breast cancer (pT1 pN0 M0) entered into a trial comparing mastectomy and breast preserving treatment. All analyses were adjusted for the factors treatment, patients' age, and tumor size. Tumor grade was defined according to Bloom and Richardson based on the sum of scores assigned to each of three histological features: 1) degree of differentiation, 2) pleomorphism, and 3) mitotic index. The relative importance of these factors with regard to disease-free survival was evaluated. In univariate as well as in multivariate analyses the pleomorphism was the only factor showing a significant effect (univariate: p = 0.0024, multivariate: p = 0.015). It was investigated how the factors should be combined to define a histological grading score which yields the best possible classification of the patients with respect to prognosis. A new grading system was defined splitting the patients into three groups: 1) pleomorphism 1; 2) pleomorphism 2 or pleomorphism 3 and mitotic index 1; 3) pleomorphism 3 and mitotic index 2 or 3. This yields a good classification of the patients with respect to prognosis (p = 0.0004). The prognostic effect of this score was compared with the effects of the grading systems proposed in the literature. According to Bloom and Richardson and in the modified version by Schauer and Weiss, grading is based on the sum of scores of the various histological factors. Therefore, the strong effect of the pleomorphism was diluted in these grading definitions (Bloom and Richardson: p = 0.03, Schauer and Weiss: p = 0.028). The grading system proposed by Le Doussal et al. consists only of the scores of pleomorphism and mitotic index (p = 0.014). In summary, the factor pleomorphism showed a stronger effect on disease-free survival by itself than the grading systems proposed in the literature.
Adult↗
Quality control review for radiotherapy of small breast cancer: analysis of 708 patients in the GBSG I trial. German Breast Study Group (GBSG).
Within six years between November 1983 and December 1989 the German Breast Cancer Study Group (GBSG) conducted a prospective multicenter trial on the treatment of pT1 pN0 M0 breast carcinoma. Out of 1036 eligible patients from 69 hospitals, a total of 733 underwent breast preservation surgery and postoperative radiotherapy. A detailed quality control (QC) screening of 708 available radiotherapy records was performed by the radiotherapy reference center. The following quality control scoring system was used for all radiotherapy variables: Radiotherapy treatment "completely according to study protocol" (QC score = 0); "acceptable protocol deviations" (QC score = 1); "unacceptable protocol violations" (QC score = 2); the "overall QC score" was the worst judgement for any single quality control criterion, while the "total QC score" was the summation of all single quality control scores (range: 0 to 14). 292 (41.2%) patients were treated per protocol; 290 (41.0%) had acceptable protocol deviations; and 126 (17.8%) had unacceptable protocol violations. 107 (84.9%) single violations, 15 (11.9%) combinations of two, three (2.4%) combinations of three, and one (0.8%) combination of four unacceptable violations were observed. 564 (79.4%) patients achieved a total QC score of < or = 2, 124 (17.5%) of 3 to 5, and 20 (2.8%) of > or = 6. The criterion "radiotherapy treatment duration" had the highest rate of protocol violations, 67/708 (9.5%); other quality control criteria with protocol violations were "radiotherapy reference dose" (27 = 3.8%), "radiotherapy treatment initiation" (15 = 2.1%) and "other protocol violations" (33 = 4.7%). No protocol violations were observed for the criterion "target volume coverage". The protocol compliance improved slightly during the conduct of the study. Institutional differences in protocol compliance were observed depending upon the accrual rate, the institutional treatment preference and between academic and non-academic hospitals. After a short median follow-up of 48 months, differences in protocol compliance, i.e. protocol violations, have not resulted in a reduced disease-free survival; however, the final prognostic evaluation of the quality control review may require longer follow-up and eventually different treatment endpoints to be analyzed.
Breast Neoplasms↗
A bootstrap resampling procedure for model building: application to the Cox regression model.
A common problem in the statistical analysis of clinical studies is the selection of those variables in the framework of a regression model which might influence the outcome variable. Stepwise methods have been available for a long time, but as with many other possible strategies, there is a lot of criticism of their use. Investigations of the stability of a selected model are often called for, but usually are not carried out in a systematic way. Since analytical approaches are extremely difficult, data-dependent methods might be an useful alternative. Based on a bootstrap resampling procedure, Chen and George investigated the stability of a stepwise selection procedure in the framework of the Cox proportional hazard regression model. We extend their proposal and develop a bootstrap-model selection procedure, combining the bootstrap method with existing selection techniques such as stepwise methods. We illustrate the proposed strategy in the process of model building by using data from two cancer clinical trials featuring two different situations commonly arising in clinical research. In a brain tumour study the adjustment for covariates in an overall treatment comparison is of primary interest calling for the selection of even 'mild' effects. In a prostate cancer study we concentrate on the analysis of treatment-covariate interactions demanding that only 'strong' effects should be selected. Both variants of the strategy will be demonstrated analysing the clinical trials with a Cox model, but they can be applied in other types of regression with obvious and straightforward modifications.
Brain Neoplasms↗
Steroid receptors in ovarian carcinoma: immunohistochemical determination may lead to new aspects.
87 nonpretreated stage III/IV ovarian common epithelial carcinomas were studied for estrogen receptor (ER) and progesterone receptor (PR) content by both immunohistochemistry (IHC) and biochemical (DCC) analysis. While the DCC assay showed tumors to be receptor-positive in 62% (ER) and 66% (PR), receptor-positive malignant epithelial cells were only detected in 38% (ER) and 31% (PR) by IHC. There was only a low correlation between the semiquantitative results of ER and PR IHC and the corresponding values of DCC receptor determination. The finding of steroid receptor-positive stromal cells without any evidence of hormone receptor-positive epithelial tumor cells offers a possible explanation for discrepant results in numerous cases with obviously "false positive" results of DCC analysis. Since the considerable heterogeneity of steroid receptor expression present in many ovarian neoplasms can only be detected by IHC, it seems to be the appropriate method of ER and PR determination. Most patients were treated by both radical cytoreductive surgery (n = 76) and a platinum-based chemotherapy (n = 79). ER was not shown to be of significant prognostic value. However, survival was significantly better in patients with PR positive tumors (IHC and DCC) on univariate analysis. Residual tumor after primary surgery was the only remaining significant prognostic factor after multivariate analysis. Further studies are needed to clarify the biological function of steroid receptor-positive stromal cells in ovarian carcinomas.
Adult↗
Breast preservation versus mastectomy in early breast cancer--1991 update of the GBSG 1--protocol and prognostic factors. The German Breast Cancer Study Group.
In 1983, the German Breast Cancer Study Group (GBSG), sponsored by the Federal Ministry of Research and Technology, started a prospective multicenter trial on the treatment of early breast cancer (pT1 pN0 M0). This was preceded by a three-year reviewing period because of some novelties of medical, juristical and ethical problems in the FRG. University and, in the majority, community hospitals participated, combining all together 69 different institutions. From 11/1983 to 12/1989, 1112 patients were recruited. From 1036 patients, 733 underwent breast preservation (71%) and 303 mastectomy (29%). The randomization rate was only 6%. In 268 patients (26%) the tumor size was less than or equal to 10 mm, in 765 patients (74%) 11 to 22 mm. In 129 cases, we subdivided the tumor grading II[3] into IIa and IIb. Moreover, the immunohistochemical detection of the transmembrane proteins EGFR, p-185 and p-148 by oncogene overexpression and c-myc oncogene were undertaken in 425 breast cancers. After tumorectomy (or wide excision) and a lower axillary dissection (at least eight lymph nodes) the breast was irradiated up to 50 Gy in 25 fractions. A boost of 12 Gy was given to the tumor bed. The medial located lymph nodes were also irradiated in case of medially or centrally tumors. Quality control was performed by pathological, radiotherapeutic and methodical reference centers. Significant correlations could be demonstrated between receptor status and tumor grading, patient age and grading, and tumor size and grading. The results emphasize the central role of tumor grading among the prognostic factors. Especially the differentiation of the Bloom and Richardson score II into IIa and IIb seems to play an important role. After a median follow-up of 41 months, the frequency of local recurrences (4.4%), regional recurrences (1%) and distant metastases (4.6%) was exactly the same in both treatment groups. In multivariate analysis, only tumor size and tumor grading had a significant impact on disease-free survival. 23 patients with tumor-involved margins had a higher recurrence rate (DFS 62% versus 85% after five years). Without any impact on DFS were the other conventionally evaluated prognostic factors: age, menopausal status, hormone receptor status, histological tumor type, tumor localisation, degree of differentiation, pleomorphism, mitotic index and degree of dissociation. Among the transmembrane proteins EGFR, p-185, p-148 and c-myc, only the impact of p-185 and EGRF positivity on DSF is significant.(ABSTRACT TRUNCATED AT 400 WORDS)
Breast↗
[Initial results of the Project of the German Breast Cancer Study Group on "Breast saving therapy of the small breast cancer"].
In the German Breast Cancer Study Group (GBSG) multicenter trial "Breast preservation in small breast cancer" 1119 patients were accrued over a period of six years. The study was originally designed as a randomized trial which had to be changed into a prospective observation study. A high therapeutic standard was guaranteed by quality control. The univariate analysis of prognostic variables was the first step to a valid treatment comparison. Those factors determined as being significant were combined with the treatment effects in a multivariate analysis. The published results were obtained after a median observation time of four years.
Breast Neoplasms↗
Continuous-wave and pulsed Doppler studies of the breast: clinical results and effect of transducer frequency.
Malignant growth requires a high metabolism. This allows the differentiation of lesions by Doppler measurements of their vascularisation. In this study of 224 patients with 45 malignancies (37 breast cancers and 8 local recurrences), 87% of the cases were correctly identified. Differentiation of palpable lesions was possible in 93%. The flow in normal breast arteries was studied as well as in carcinomas, comparing continuous-wave (CW) Doppler with frequencies at 4 and 8 MHz. To improve flow evaluations in nonpalpable lesions, pulsed Doppler was used at 3 MHz and color mapping systems at 5 MHz in another 37 patients. Color Doppler at 5 MHz identified 17 of the 21 malignancies; in all cases pulsed Doppler at 3 MHz failed.
Adenofibroma↗
[Analysis of a method for Doppler study of the female breast].
Besides characteristic morphological differences, carcinomas of the breast show remarkable changes of vascularity, which are essential for their enhanced metabolism. High-frequency CW Doppler allows to investigate normal and pathological vascularisation in the breast. In our basic study we examined 200 patients, 37 with breast malignancies (6 non-palpable lesions). 33 of the carcinomas showed pathological vascularisation. In an extended examination procedure we investigated also normal breast vascularisation and compared it with blood flow in lesions. We developed therefrom an easy and rational method which allows physiological blood flow measurements as well as a differentiation of breast lesions within a few minutes' time.
Adenofibroma↗
[Adjuvant chemotherapy of breast cancer with the CMFV protocol].
Adjuvant CMFV therapy was administered from 1975 to 1984 at the Department of Gynaecology and Obstetrics of the University of Erlangen in 331 patients from a patient population, who underwent an operation with the intention of curing invasive breast cancer. Six cycles of this therapy were administered to 224 women. Only these patients were considered in the evaluation. 538 patients without axillary lymph node metastases and without adjuvant therapy served as reference population. The significance of adjuvant CMFV therapy in relation to the lymph node and menopausal status was investigated in a retrospective analysis. It was shown, that the five-year actual survivals in the group of premenopausal patients with one to three affected lymph nodes and CMFV therapy (n = 60), did not differ significantly from the group of women with premenopausally negative lymph nodes without adjuvant therapy (n = 198) (87.7% versus 88.2%). On the other hand, in the postmenopausal patients, the five-year actual survivals for the corresponding groups were 65.9% and 83.2%, respectively. The difference was significant. The results indicate, that adjuvant CMFV therapy improves the prognosis in premenopausal women, above all in cases with one to three affected lymph nodes. In the postmenopausal patients, a comparable effect could not be demonstrated in this group of patients.
Adult↗
[Differential breast diagnosis using CW-Doppler ultrasound].
There is no method that allows satisfactory differentiation between benign and malignant breast lesions. We were able to differentiate 94% of palpable malignant tumours with CW-doppler ultrasound, which helps to increase the efficiency of clinical examinations, breast sonography and mammography. Two hundred patients were examined with an 8 MHz CW-doppler probe. The symmetry of arterial vessels and flow velocity in normal breasts is very high. Carcinomas appear as areas with localized flow increase. Only in two normal patients was a minimal focus of two arteries found.
Breast Neoplasms↗
CA-125 serum concentrations during the menstrual cycle.
CA-125 is an antigenic determinant expressed on ovarian cancer cells and serves as serum marker in patients with ovarian cancer. It has also been detected, however, in serum of healthy women and in patients with benign gynecologic diseases. Previous studies in patients with ovarian hyperstimulation syndrome suggested that the production of CA-125 is correlated with proliferative ovarian activity. In this study, we describe the pattern of CA-125 secretion in 13 healthy women during menstrual cycle and during hormonal contraceptive treatment. That pattern is characterized by an increase of CA-125 serum concentrations parallel to the growth of the dominant follicle. It was not observed during hormonal contraceptive treatment. We conclude that CA-125 serum levels during menstrual cycle seem to be dependent upon the cyclic changes in the female genital tract.
Adult↗
[24-hour CA 15/3 serum concentrations in patients with primary and metastasizing breast cancer].
Serum determinations of tumor-associated antigens in breast cancer patients are utilized for detection of metastases as well as prediction of treatment response. That is critically dependent on the validity of single daily marker determination. In our study in patients suffering from primary or metastatic breast cancer we could demonstrate fluctuations of antigens detected with the two monoclonal antibodies 115D8 and DF3 (CA-15/3) during a 24 h observation period. Beside methodical inaccuracies those fluctuating serum concentrations might be related to biological phenomena. However, on basis of our data no intra- or interindividual rhythms could be exhibited.
Antigens, Neoplasm↗