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  • breast cancer  (55)
  • Springer  (55)
  • 1990-1994  (55)
  • 1985-1989
  • 1970-1974
  • 1992  (55)
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  • 1990-1994  (55)
  • 1985-1989
  • 1970-1974
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1824-3096
    Keywords: Dermatoglyphics ; asymmetry ; cleft lip and palate ; Cooley's anemia ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The amount of asymmetry in various digital and palmar characters found in healthy and pathological individuals (presenting Cooley's anemia, cleft lip, cleft palate and breast cancer) was examined. Males with cleft palate presented higher asymmetry index values than did healthy males. No great differences were found in the other pathologies, while different behaviour in the two sexes was noted.
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  • 2
    ISSN: 1573-8280
    Keywords: adoptive immunotherapy ; breast cancer ; interleukin-2 ; pleural effusion ; tumor-infiltrating lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We developed a local AIT using PEL cultured with TCGF combined with preadministration of OK-432. Twenty-six patients of breast cancer with pleural effusion have been treated with this therapy since 1983. PEL expanded and tumor cells collapsed by day 9 in culture with TCGF. Cultured PEL possessed significantly higher cytotoxic activity against autologous tumor cells than PBL cultured in the same condition (p 〈 0.05), but there was no difference between their cytotoxic activities against K562. The proliferation rate of PEL obtained after intrapleural administration of OK-432 was higher than that obtained before OK-432 (p 〈 0.01). Moreover, the cytotoxic activities against both autologous tumor and K562 of cultured PEL obtained after OK-432 administration was significantly (p 〈 0.05) higher than those cultured PEL obtained before. Cultured PEL (1 x 108 - 6 x 109) were transferred into the pleural cavity after the intrapleural administration of OK-432 (1–5 KE). The volume of pleural effusion increased temporarily after the administration of OK-432 but significantly (p 〈 0.01) decreased after AIT. Tumor cells disappeared cytologically in 22 patients at the last puncture of pleural effusion. Pleural effusion disappeared completely in 19 of 26 patients and decreased by more than 50% in volume in 6 patients. Performance status improved in 22 patients. The response rate for OK-432-combined AIT in the present study was 96%. The survival period of the patients treated by OK-432-combined AIT in this trial was significantly (p 〈 0.002) prolonged compared to that of the patients receiving chemotherapy alone. The side effects were fever and general malaise after OK-432 administration but no critical toxicity was observed.
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  • 3
    ISSN: 1573-7217
    Keywords: breast cancer ; human milk fat globule antibodies ; immunohistochemistry ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The status of axillary lymph nodes in patients with breast cancer is important prognostically but does not identify all patients who will have long or short survival. To determine if the immunohistochemical reaction of tumor cells to human milk fat globule (HMFG) antibodies will define prognosis more specifically, we examined patients with node-negative disease and patients with more than three positive nodes, the extremes of the prognostic spectrum. In both node-negative and node-positive groups, patients who relapsed were matched by age at diagnosis, tumor size, histologic type, and receptor status, with patients who remained disease-free for a minimum of 48 months. Patients with poor survival had a higher proportion of poorly differentiated cancers. The ability to generate antigens recognized by HMFG antibodies was decreased in patients with recurrent disease, but this was significant only in patients with node-positive tumors. Tumors of patients who remained disease-free were more likely to have a pattern of membrane staining, while cytoplasmic staining was more frequent in those who relapsed. The results suggest that immunohistologic response to HMFG antibodies may assist in identifying cancers with poor prognosis, supplementing the prediction derived from node status.
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  • 4
    ISSN: 1573-7217
    Keywords: breast fluids ; epithelial membrane antigen ; polymorphic epithelial mucin ; breast cancer ; witch's milks
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have examined breast fluids from non-lactating women and male neonates for the expression of epithelial membrane antigen (EMA), also termed polymorphic epithelial mucin (PEM). All fluids exhibited significant amounts of EMA as demonstrated by immunoblot analyses and enzyme immunoassay. EMA was present in the breast fluids of both pre- and post-menopausal women, and these results suggest that nipple aspirates could provide an easily accessible source of antigen for assessing the value of EMA as a tumor marker both before and after various therapeutic modalities. The presence of EMA in the ‘witch's milks’ indicates that full maturation of the breast is not a prerequisite for antigen expression in breast tissue.
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  • 5
    ISSN: 1573-7217
    Keywords: tamoxifen ; breast cancer ; body weight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Changes in body weight have been studied in 92 consecutive patients with primary breast cancer from the time of initial diagnosis and treatment. Sixty patients receiving tamoxifen were compared with 32 controls receiving no hormone treatment. Weight gain was seen in both groups, but was greater in the group receiving tamoxifen. Premenopausal women receiving tamoxifen had greater weight gain than postmenopausal women on tamoxifen therapy.
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  • 6
    ISSN: 1573-7217
    Keywords: breast cancer ; cytogenetics ; estrogen receptor ; genetic evolution ; ploidy ; progesterone receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of estrogen (ER) and progesterone (PR) receptors was assayed by steroid binding in a series of 95 malignant breast tumors, for which the analysis of chromosome aberrations was performed and allowed the reconstruction of their chromosomal evolution. It was shown that breast tumors undergo a progressive loss of chromosomes, with occasionally one and rarely two endoreduplications. Chromosome losses were often the consequence of rearrangements, and the rate of rearranged chromosomes, which increases progressively, appeared as a possible indicator of tumor progression. The distribution of ER and PR values in the sample of 95 tumors was compared to that of a larger control series of consecutive cases: 598 for ER and 460 for PR. The similarities of the distributions indicated that the sample of 95 tumors was representative of the general population of breast cancers. The levels of ER and PR expression were very strongly and negatively correlated to the rate of rearranged chromosomes, but not to the modal number of chromosomes. However, when tumors having either undergone endoreduplication or not (〉50 or 〈51 chromosomes, respectively) were considered separately, a significant correlation between ER and PR expression and chromosome number was found within each group. Finally, breast cancers were subdivided into 4 stages of cytogenetic evolution, from the least to the most evolved: stage 1: ≤50 chromosomes, 〈25% rearranged chromosomes; stage 2: 〉50 chromosomes, 〈25% rearranged chromosomes; stage 3: ≤50 chromosomes, 〉25% rearranged chromosomes; stage 4: 〉50 chromsomes, 〉25% rearranged chromosomes. The rate of negative or low ER values (〈500 fmol/g tissue) was 10% in stage 1; 16% in stage 2; 45% in stage 3; 82% in stage 4. The corresponding rates for negative or low PR values (〈500 fmol/g tissue) were 17%; 28%; 60%; and 91%. These data illuminate the probable role of genetic evolution in determining the variations of biological prognostic parameters of breast cancer, such as steroid hormone receptors.
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  • 7
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptors ; steroid receptors ; quality control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study investigates the effect of freezing and storage of tissue and subcellular fractions on the measurement of epidermal growth factor receptors (EGF-r); compares competition binding and single saturating dose assays (SSD) for quantitating EGF-r levels; investigates several tissues as potential quality control; and examines the relationship between EGF-r and hormone receptor expression in human breast cancers. Mouse and calf uterine cell membranes were preferred sources of quality control tissue with similar levels of high affinity EGF-r to human breast cancer tissue (〈150–200 fmol/mg membrane protein). Studies using pooled mouse uterine tissues indicated a loss of 40% in EGF-r activity following a single −20°C freeze/thaw cycle, while a breast cancer tissue showed a 75% loss, independent of storage temperature (liquid nitrogen, −70°C, −20°C). A single freeze/thaw cycle of mouse uterine broken cell pellets (nuclei plus membrane fraction) again indicated a loss of EGF-r irrespective of storage temperature (43% loss at −70°C, 52% loss at −20°C). In most cases irrespective of the tissue type or tissue fraction being stored, the length of storage had little impact on the extent of the loss in activity. A second freeze/thaw cycle of intact tissue, or freezing of broken cell pellets from a previously-frozen tissue, led to a further major or total loss of the remaining EGF-r. Overall these results are commensurate with the published effects of freezing and storage on estrogen receptor measurement. In addition, our studies suggest that the most suitable procedure for assaying frozen breast cancer specimens for EGF-r levels in conjunction with steroid receptor quantitation is to prepare and assay both cytosol and membrane fractions for their respective receptor content without further storage. A concordance of 86% was found in 44 breast cancers assayed for EGF-r by saturation analysis and SSD. Statistically significant inverse relationships were found between EGF-r and estrogen and progesterone receptor levels in a study of approximately 350 breast cancer patients. No association was found with tumor stage or diameter, axillary node involvement, or patient age.
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  • 8
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen ; MCF-7 cells ; regulation ; sulfotransferase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The importance of the steroid hormone microenvironment within cells is now recognised in studies on endocrine-related neoplasms such as breast cancer. This focuses attention on ezymes which control the intracellular levels of estradiol-17β (E2). One such enzyme, estrogen sulfotransferase, which converts E2 to inactive E2-3 sulfate, has now been shown to be regulated by estrogen in MCF-7 human mammary cancer cells. Hydroxysteroid sulfotransferase, which sulfurylates the adrenal-derived estrogen 5-androstene-3β,17β-diol, is also under estrogen control. Evidence is provided which shows that one function of these enzymes may involve elimination of estrogen from the cell following processing of the ligand-charged estrogen receptor (ER).
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 22 (1992), S. 187-191 
    ISSN: 1573-7217
    Keywords: breast cancer ; data representation ; multivariate variable-selection ; prognostic factors ; validation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This special issue of Breast Cancer Research and Treatment addresses the topic of how to evaluate new prognostic factors for breast cancer, and how the information provided by these new factors might be integrated with traditional factors to make better treatment decisions for these patients. Although the focus is on breast cancer, the techniques described are equally applicable to any situation involving survival or failure over time.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 23 (1992), S. 29-41 
    ISSN: 1573-7217
    Keywords: animal models ; breast cancer ; contraceptive steroids ; dogs ; humans ; mammary tumorigenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The safety of synthetic steroid hormones to be used for contraception in the human female is tested in rats, beagle dogs, and (once marketing starts) in monkeys. Because early studies did not show a mammary tumor stimulating effect in the human, in contrast to findings in the dog, many objections have been raised to the use of the dog for these toxicity studies. It has been claimed that the dog is unique in its sensitivity to the mammary tumor promoting effect of progestins and that this tumorigenic effect results from progestin-induced growth hormone (GH) induction. A thorough review of the literature does not support these claims. Tumor stimulatory effects of progesterone or synthetic progestins can be observed under some conditions in rodents as well as in cats and monkeys. In addition, recent evidence suggests a role for progesterone in mammary tumorigenesis in the human, and contraceptive steroids may also not be completely without risk. While the suggested role for GH in dog mammary tumorigenesis is far from proven, such a role cannot be excluded in the other species. Whether tumor stimulatory effects of sex steroids are based upon induction of proliferation in target cells or upon genotoxic effects or both is not yet certain.
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  • 11
    ISSN: 1573-7217
    Keywords: aminoglutethimide ; aromatase inhibition ; breast cancer ; 4-hydroxyandrostenedione ; oestrogen ; oestrone sulphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p〈0.05). Plasma oestrone was suppressed by a mean of 40.6% (p〈0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p〈0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.
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  • 12
    ISSN: 1573-7217
    Keywords: cathepsin-D ; proliferative activity ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mitogenic properties have been demonstratedin vitro for the lysosomal acidic protease cathepsin-D (cath-D). We investigated possible relationships between cath-D cytosol cell content and tumor proliferative activity in a series of 129 operable breast cancer patients. For total cytosol cath-D evaluation, a solid phase two-site immunoradiometric assay was utilized on tumor cell cytosol obtained for hormone receptor assay (DCC method). The percentage of S-phase cells was analyzed by 3H-thymidine autoradiographic assay. Median 3H-thymidine Labeling Index (3H-Tdr-LI) of the series was 2.7%; median cath-D content resulted 57 pmol/mg of protein cytosol and was significantly higher in node-positive with respect to the node-negative subgroup (p〈0.03). When classified in low, intermediate or high tumor cath-D content and slow or fast proliferative activity (cut-off: median values of the series), no significant agreement was found between the two variables. Statistical analysis, however, showed that a significant inverse correlation existed in node positive tumors between cath-D and 3H-Tdr-LI values which was even more evident in N-positive high estrogen receptor-positive (ER+) cases (coefficient of correlation = −0.6828; p=0.0001). Cytosol cath-D content cannot be generally proposed as a direct marker of proliferative activity for operable breast cancer.
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  • 13
    ISSN: 1573-7217
    Keywords: breast cancer ; differentiation ; immunohistochemistry ; milk fat globule antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemical studies of human breast cancers using human milk fat globule (HMFG) antibodies are divergent regarding the association with histologic differentiation. To clarify this association 392 tumors were assessed using two antibodies, HMFG-1 and HMFG-2. In half the tumors studied the tissue reaction to both antibodies was the same and in 63% the site of reaction was identical. Using both univariate and multivariate statistics, a highly significant association was recorded between membrane staining and well differentiated cancers and cytoplasmic staining and poor differentiation. Well differentiated tumors contained significantly more reactive cells. Complementing these findings was the association between age at diagnosis, tumor stage, and estrogen receptor status and differentiation. It is possible that immunohistochemical analysis with HMFG antibodies will provide better characterization of tumor differentiation than morphologic interpretation.
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  • 14
    ISSN: 1573-7225
    Keywords: Age at diagnosis ; breast cancer ; case-control ; diet ; menopause ; Singapore
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case-control study was conducted among Singapore Chinese women, comprised of 200 histologically confirmed cases of breast cancer and 420 hospital controls. Subjects were interviewed on family history of breast cancer, social and demographic characteristics, reproductive history, and diet one year prior to interview. Differences in risk factors were observed according to menopausal status. In the premenopausal group, the most consistently significant nondietary effect was an increased risk with late age at first birth. In postmenopausal women, the most consistent nondietary effects were increased risks with nulliparity, tall stature, high educational status, and a family history of breast cancer. In premenopausal women, the strongest dietary effects were low risks with high intakes of polyunsaturated fatty acids (PUFA), β-carotene, soya protein as a proportion of all protein, and a high risk with high red-meat intake. No dietary effects were observed in postmenopausal women. Examination of effects by 10-year age groups suggested that the differences in the effects of age at first birth, nulliparity, height, education, β-carotene intake, and PUFA intake between premenopausal and postmenopausal women were at least partly attributable to age-related differences in the baseline distributions of these variables. The variation in the effects of red meat and soya protein appeared to be attributable mainly to menopausal status itself, which is consistent with the hypothesis that these factors operate on risk by way of hormonal mechanisms.
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  • 15
    ISSN: 1573-7276
    Keywords: breast cancer ; axillary nodes ; tumour area ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The tumour-load in the axilla of breast cancer patients is classically measured from the number of tumour-bearing nodes present, which is then used to assess prognosis. This preliminary morphometric study on 73 cases of breast carcinoma for which standardized axillary dissection specimens were available shows that the total tumour load, measured from the sum of the tumour area (cm2) in hilar nodal sections, gives a redistribution of the patients; one that may provide better prognostic information in particular in women with a high tumour load. In those with four or more nodes involved the actual number is said to give little prognostic discrimination at 4 years post-operatively, as was demonstrated in this series. In contrast, using data from the same patients, the risk of death by this time increased steadily with increasing tumour area.
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  • 16
    ISSN: 1573-7217
    Keywords: breast cancer ; HPV ; in situ hybridization ; PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histological sections from paraffin-embedded breast carcinoma and axillary lymph nodes were examined for the presence of human papillomaviruses by two different techniques: the polymerase chain reaction (PCR) and thein situ hybridization with biotin-labelled probes. By PCR we detected HPV 16 DNA sequences in 29.4% of breast tumours and in some metastatic lymph nodes, though we were unable to identify any HPV DNA sequences byin situ hybridization. These results suggest that HPV's could play a role in the genesis of breast neoplasia.
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  • 17
    ISSN: 1573-7217
    Keywords: breast cancer ; breast fluid ; milk proteins ; prolactin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Breast secretions can be classified into two types according to their major protein components. Type I fluids contain Zn-α2-glycoprotein, apolipoprotein D, and gross cystic disease fluid protein-15, while Type II fluids are characterized by the presence of lactoferrin, lysozyme, and α-lactalbumin. In this study, the polypeptide composition of breast secretions from 719 nonlactating women was evaluated by using polyacrylamide gel electrophoresis. The required amount for the analysis (1 µl) was obtained from 50% of control women and from 75% of women with mammary disease. There were more secretors in premenopausal than in postmenopausal women, as well as in parous than in nulliparous women. Evaluation of factors affecting protein composition of breast secretions revealed that Type II fluids were found in the majority of women who had given birth in the last four years and in a high proportion of oral contraceptive users. After excluding both of these groups, Type II fluids were detected in 47% of patients with breast cancer, but only in 8% of control women and in 16% of women with benign breast diseases. Taken together, these results suggest that protein analysis of breast secretions could be an useful tool for the study of breast pathologies.
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  • 18
    ISSN: 1573-7217
    Keywords: breast cancer ; cell lines ; cytosols ; differentiation ; placental isoferritin ; proliferation ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Placental isoferritin (PLF), an acidic isoform of ferritin, and its unique superheavy chain p43 have been recently described to be synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of ‘normal’ ferritin in breast cancer tissue, degree of differentiation, and prognosis, we have tried to evaluate the correlation of p43 in the cytosol of 122 breast cancer samples with commonly applied prognostic factors and features of proliferation and differentiation. In parallel, we investigated the correlation of p43 expression in MCF-7 and T47-D breast cancer cell lines during proliferation induced by estradiol plus fetal calf serum (assessed by3H-thymidine incorporation), compared to p43 expression in stationary non-stimulated cell cultures. The levels of p43 in breast cancer cytosols correlated significantly negatively with tumor size (p=0.0001), histologic grading (p=0.0038), nuclear pleomorphism (p=0.0019), rate of mitosis (p=0.0002), and lymphocytic reaction (p=0.0001), and significantly directly with the estrogen receptor status (p=0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multivariate Cox model. In accordance with the observed negative correlation of features of differentiation vs. p43 expression, induction of proliferation by estradiol plus FCS added to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. Expression of p43 in estrogen and FCS-absent media revealed also a decrease in relation to a low spontaneous proliferation. However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen-stimulated proliferation. Ourin vitro and cytosol results confirm recent clinical observations describing an inverse correlation of p43 synthesis with the degree of proliferation and differentiation in breast cancer. However, the pathologic mechanisms leading to this phenomenon as well as the negative correlation with lymphocytic infiltration are still unclear and need to be further elucidated.
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  • 19
    ISSN: 1573-7217
    Keywords: adriamycin ; breast cancer ; chemosensitivity assay ; lonidamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lonidamine is a new potential chemotherapeutic agent, relatively non-toxic, that can positively modulate the efficacy of several antineoplastic drugs. We evaluated the response of two established human breast cancer cell lines (MCF-7 and BRC-230) and of 20 primary breast cancer cell lines to lonidamine, either alone or in combination with adriamycin, the drug most widely used in the management of breast cancer. Different schedules were tested by varying either concentration of the drugs (LND: 10–150µg/ml; ADM: 0.10–0.15µg/ml), or time of exposure (1–96 hours), or sequence of administration (ADM → LND; LND → ADM; ADM + LND). Our results indicate slight sensitivity of the cell lines to lonidamine when used alone, whereas an increase of efficacy was noted when lonidamine was added for at least 24 hours after a 4 hour exposure to adriamycin. Such efficacy was significantly greater than that expected from an additive effect between the two drugs. We conclude that lonidamine, when given according to an appropriate schedule, enhances,in vitro, the efficacy of adriamycin. A correct employment of lonidamine in the management of breast cancer might therefore potentiate the therapeutic effect of adriamycin.
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  • 20
    ISSN: 1573-7217
    Keywords: breast cancer ; family history ; reproductive history ; diet ; obesity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 24 (1992), S. 75-79 
    ISSN: 1573-7217
    Keywords: breast cancer ; lactic acidosis ; metabolic complication ; oncologic emergency ; paraneoplastic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case is presented of a patient with longstanding metastatic breast cancer whose condition suddenly deteriorated due to hypercalcemia and severe lactic acidosis which rapidly proved fatal. Postmortem examination showed no explanation for the lactic acidosis other than extensive metastatic disease. A review of the rare syndrome of malignancy-induced lactic acidosis is presented with particular emphasis on the 5 other cases reported in association with metastatic breast cancer. Theories of pathogenesis and management controversies are discussed.
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  • 22
    ISSN: 1573-7217
    Keywords: c-erbB-2 protein ; breast cancer ; tumor marker ; enzyme immunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The c-erbB-2 protein was measured in sera of patients with breast cancer or benign breast diseases to study the significance of this protein as a tumor marker. The mean value and positive rate for this protein (assuming 20 U/ml as the cut-off value) were 11.8 U/ml (0%) in benign breast disease (n=30), 11.8 U/ml (3.1%) in stage I/II primary breast cancer (n=64), 38.2 U/ml (29.4%) in stage III/IV primary breast cancer (n=17), 17.9 U/ml (33.3%) in locally recurrent breast cancer (n=12), 298.4 U/ml (51.0%) in recurrent breast cancer with distant metastases (n=51), and 12.9 U/ml (0%) in those with no evidence of recurrence (n=57). Thus, the serum c-erbB-2 protein level was significantly higher in the distant metastatic group. In patients with distant metastases, there was a close association between expression of c-erbB-2 protein in the primary tumor and the serum c-erbB-2 protein level. On the basis of these results, serum c-erbB-2 protein was thought to be useful as a tumor marker for postoperative monitoring of breast cancer, especially in patients positive for expression of this protein in primary cancer tissue.
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  • 23
    ISSN: 1573-7217
    Keywords: androgens ; breast cancer ; medroxyprogesterone acetate ; 50:50 poly[DL-lactide-co-glycolide] microspheres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since our previous findings had indicated that the androgenic steroid medroxyprogesterone acetate (MPA) exerts potent inhibitory effects on 7,12-dimethylbenz(a)anthracene (DMBA)-induced tumor growth, we have studied the effect of low doses of MPA released from Depo-Provera and from 50:50 poly[DL-lactide-co-glycolide] microspheres in the same DMBA-induced tumor model. The present data show that single subcutaneous injection of a 4-month controlled-release formulation of biodegradable 50:50 poly[DL-lactide-co-glycolide] microspheres containing 10 mg of MPA giving serum levels of 3.14±0.32 ng/ml (8.12±0.83 nM) MPA causes a maximal or near-maximal 60% inhibition of tumor growth measured 56 days later. Such data suggest that controlled-release formulations giving constant and low blood levels of MPA could be used for the treatment of breast cancer in women. Such a low concentration of MPA should avoid the side effects observed with the high doses of the compound.
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  • 24
    ISSN: 1573-7217
    Keywords: aminoglutethimide ; breast cancer ; endocrine therapy ; medroxyprogesterone acetate ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to evaluate the efficacy of two different sequences of second and third line hormonotherapy in advanced post-menopausal breast cancer, 257 women aged 36–91 years (mean age: 63.6 years) who had become resistant to tamoxifen (TAM), entered into a multicenter randomized trial comparing two different regimens: 1) Aminoglutethimide (Ag) 500 mg/day with hydrocortisone supplementation from 30 to 60 mg/day; and 2) oral medroxyprogesterone acetate (MPA) 500 mg twice a day. 250 patients were evaluated following second line hormone therapy and, after cross-over, 128 following third line hormonotherapy. No significant difference was observed, during either second or third line therapies, for toxicity, survival, or response rate; however, in both second and third line therapies the median time to progression was significantly longer with Ag therapy.
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  • 25
    ISSN: 1573-7217
    Keywords: flow cytometry ; DNA ploidy ; S-phase fraction ; estrogen receptor ; breast cancer ; prognosis ; stage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prospective prognostic significance of flow cytometry derived DNA-ploidy status, the level of the S-phase fraction (SPF), estrogen receptor (ER) content, and combinations of these factors, was evaluated with respect to overall survival (OS) in a series of 516 breast cancer patients who were without signs of residual or distant disease after primary completed treatment. The median duration of survival follow-up time was ten years (range, 95–148 months) for surviving patients. Of the single factors, ER was the only significant predictor among node-negative patients; the ten-year OS rate was 71% in cases with ER-rich tumors vs. 62% for ER-poor tumors (p=0.03). Where tumors were both non-diploid and ER-poor, the ten-year OS rate was 58%, as compared to 75% for the remaining node-negative patients (p=0.003), who constituted a low-risk group whose survival was comparable with that in the age-matched normal population. Among patients with 1–3 positive nodes, the ten-year OS rate was 65% in patients whose tumors had an SPF 〈7.3% vs. 50% if the SPF was ≥7.3% (p=0.01), and 58% in cases with ER-rich tumors vs. 45% where the tumors were ER-poor (p=0.02). In a multivariate analysis, apart from age and menopausal status the combination of ploidy status and ER content was the significant (p=0.002) predictor of OS in node-negative patients. Thus, combining ploidy and ER status, both of which are variables easily determined, enabled the selection of a subgroup of patients at high risk of relapse and reduced survival whose prognosis should be improved by effective adjuvant systemic treatment, whereas the remaining low risk N0 patients can not be expected to derive any survival benefit from adjuvant therapy since their predicted survival is already on a par with that of the general population.
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  • 26
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    ISSN: 1573-7217
    Keywords: breast cancer ; high-dose chemotherapy ; hormone therapy ; new therapy ; new drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Progress in the treatment of breast cancer developed along multiple directions of research during the last decade. The concept of dose-intensity was addressed through retrospective analyses and prospective randomized trials. It was confirmed that dose-intensity correlates with higher response rates, but the effect of dose-intensive treatments on survival still needs to be established. Several new cytotoxic drugs have appeared during the last several years. Taxol, navelbine, and anthrapyrazole CI-941 have been found to have major efficacy against breast cancer, with response rates exceeding 50%. Amonafide, lonidamine, and elliptinium analogs were also shown to be effective, although to a lesser degree. Antiestrogen analogs, new aromatase inhibitors, and LHRH analogs are recent developments that are changing the face of hormonal therapy. Monoclonal antibodies are being developed and evaluated for tumor imaging applications and as vehicles for specific antitumor agents (cytotoxics, radioisotopes, and toxins). Expanding knowledge about the basic biology of breast cancer has led to the identification of growth factors and their receptors, which may be exploited for therapeutic purposes in the not too distant future.
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  • 27
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    Breast cancer research and treatment 21 (1992), S. 15-26 
    ISSN: 1573-7217
    Keywords: breast cancer ; endocrine therapy ; hormone therapy ; metastases ; review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary More than 45,000 women will die of metastatic breast cancer in the United States in 1991. Endocrine therapy remains a major option for treatment of such patients, and results in complete plus partial response rates of 30% with a median duration of approximately one year. Postmenopausal status, increased age, a prolonged disease-free interval, bone and soft tissue metastases, and positive estrogen and progesterone receptors are all associated with an increased response to endocrine therapy. The use of additive hormonal therapy, specifically antiestrogens, progestins, and aromatase inhibitors, have replaced surgical ablative procedures in the majority of patients; response rates to antiestrogen therapy, progestin therapy, and aromatase inhibitors are similar, but antiestrogens have generally been associated with the most favorable therapeutic index. At present, there is no convincing evidence that either combinations of endocrine therapies or endocrine therapy combined with chemotherapy are associated with an improvement in survival for patients with metastatic disease. Future research efforts directed at defining the molecular mechanisms of endocrine activity should facilitate clinical trials of newer and potentially more effective agents. All patients with metastatic breast cancer should be considered for at least one trial of endocrine therapy provided their metastatic disease is not rapidly progressive or life-threatening.
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  • 28
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    Breast cancer research and treatment 21 (1992), S. 27-34 
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; combination ; dose intensification ; new drugs ; outpatient treatment ; quality of life ; single agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The treatment of advanced breast cancer has undergone relatively little change in the past decade. Reasons for such a static situation are the sobering realization that even effective chemotherapeutic regimens have had a minor impact on survival, and the paucity of new effective agents that have been introduced since initial combination treatments. Based in part on this lack of progress, in recent yearsdose-intensification in search of a curative strategy has been widely adopted. Its role remains to be defined, but ultimately it is likely to be relegated to situations where tumor burdens have been effectively reduced. This reduction in burden may not currently be feasible in many advanced presentations. Outpatient efforts will therefore focus on the following: 1) employing single agents optimally (e.g. infusion 5-fluorouracil), 2) using regimens which integrate new drugs with activity (e.g. taxol), and 3) testing measures which may improve the quality of life (e.g. bisphosphonates in the presence of bone metastases). Although one cannot approach the treatment of advanced breast cancer with the (misplaced) optimism of two decades ago, the expanded armamentarium currently available should lead to a more rational application of chemotherapy. Treatments will increasingly be based on the biology of the cancer, and on the therapeutic index and action of the drugs.
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  • 29
    ISSN: 1573-7225
    Keywords: Attributable risk ; breast cancer ; Hawaii ; lung cancer ; prostate cancer ; saturated fat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The dietary data from case-control studies of breast, prostate, and lung cancer in Hawaii revealed that saturated fat was a risk factor for these malignancies. The dietary intakes from the three studies were used to calculate the attributable risk (AR) due to saturated fat. For all ethnic groups combined, the ARs for the highest quartiles of intake were 14.9 percent for female breast cancer, 13.0 percent for prostate cancer, and 23.1 percent for male lung cancer. Our results suggested that a reduction of saturated fat to the lowest quartiles of intake could result in a 10 to 20 percent decrease in risk for these three cancers in Hawaii. We also examined the ethnic-specific risks associated with saturated fat consumption among the Japanese and the Caucasians in the three studies. The ARs for the highest quartiles of intake were notably higher among the Caucasians than the Japanese, primarily due to the difference in their dietary patterns. Although the calculated AR due to saturated fat was higher among the Caucasians than among the Japanese, all persons in the population would derive considerable benefit by reducing their intake of this nutrient.
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  • 30
    ISSN: 1573-7225
    Keywords: α-carotene ; α-tocopherol ; benign breast disease ; β-carotene ; breast cancer ; dietary intake ; γ-tocopherol ; lycopene ; serum ; United States
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: We investigated the relationship between serum levels of retinol, β-carotene, α-carotene, lycopene, α-tocopherol, and γ-tocopherol as well as intakes of retinol, carotene, and vitamin E and the risks of breast cancer and proliferative benign breast disease (BBD) in a case-control study of postmenopausal women in the Boston, MA (United States) area. Serum nutrient data were available for 377 women with newly diagnosed stage I or II breast cancer and 173 women with proliferative BBD. Controls were 403 women who were evaluated at the same institutions but did not require a breast biopsy or whose biopsy revealed nonproliferative BBD. We observed no significant associations between serum levels of these micronutrients and risk of proliferative BBD or breast cancer. The risk of breast cancer was decreased among women in the highest quintile of intake of vitamin E from food sources only (odds ratio [OR] for the highest quintile = 0.4,95 percent confidence interval [CI]=0.2–0.9; P, trend across quintiles = 0.02) but less so for total vitamin E intake including supplements (OR=0.7, CI=0.4–1.3; P, trend = 0.07).
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  • 31
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    Cancer causes & control 3 (1992), S. 517-525 
    ISSN: 1573-7225
    Keywords: A typical hyperplasia ; breast cancer ; meta-analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The purpose of this paper is to examine critically the evidence that atypical hyperplasia (AH) is a risk factor for breast cancer. First, we appraised studies that have examined the association between AH and breast cancer risk for their adherence to widely accepted standards for the conduct of research. Second, we examined the a vailable evidence to determine the plausibility of an association between AH and breast cancer risk using the guidelines proposed by Bradford Hill. A total of 18 studies (11 cohort studies, two case-control studies, and five cross-sectional studies) were found that were published in the English language from January 1960 to March 1992 that examined the association of AH as a distinct entity and breast cancer risk. A systematic approach was adopted to examine the collected studies for their adherence to methodologic standards, which showed wide variation among studies. A meta-analysis was carried out, based on a total sample size of 182,980 women. Of 16 studies that gave point estimates of risk, 14 exceeded unity and 12 were significantly different from unity. The pooled estimate from all studies of the association between AH and breast cancer, gave an overall odds ratio (OR) of 3.67 (95 percent confidence interval = 3.16–4.26). The test of the hypothesis of homogeneous association was rejected (χ2 = 151.6, df = 14, P〈0.0001), indicating significant variability among the ORs of individual studies. The conclusions from the application of the Bradford Hill criteria indicated strongly that AH is a risk factor for breast cancer.
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  • 32
    ISSN: 1573-7276
    Keywords: breast cancer ; dietary fat ; nude mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The effects of inoculation site and dietary fat intake on the growth and metastasis of the MDA-MB-435 human breast cancer cell line were studied in athymic nude mice. The tumor cells, 1 × 106, were injected into either a right-sided thoracic or inguinal mammary fat pad (mfp), and 1 week later mice were randomly assigned to a high-fat (HF), 23% corn oil, or a low-fat (LF), 5% corn oil, diet. There were 30 mice in the HF, and 30 in the LF subgroups from each of the two inoculation site groups. The experiment was terminated 15 weeks after the tumor cell inoculations. Within the thoracic mfp-injected group, a HF diet reduced latency, increased growth rate at the primary site, and enhanced metastasis to regional lymph nodes, lungs, and intra-abdominal sites. For mice inoculated into an inguinal mfp, fat intake affected neither primary nor metastatic tumor development and growth; in both subgroups lung metastasis was significantly less than in the HF-fed, thoracic mfp-injected subgroup. The histological features of the lung metastases were consistent with a vascular mode of spread, whereas the extensive intra-abdominal lymph node involvement observed in mice with inguinal mfp tumors was in keeping with lymphatic-borne metastases.
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  • 33
    ISSN: 1573-0646
    Keywords: multidrug resistance ; toremifene ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The enhanced accumulation of doxorubicin by agents known to reverse multidrug resistance provides a good functional test for evaluating modulating activity. In the present study, the non-steroidal triphenylethylene toremifene selectively increased doxorubicin accumulation in multidrug resistant estrogen receptor negative MDA A-1 human breast cells compared to the MDA 231 wild type cells. MDA A-1 cells were noted to be 1,000 fold resistant to doxorubicin (IC 50=〈 0.1μg/ml MDA 231; IC 50=100μg/ml MDA A-1). Total accumulation of doxorubicin, expressed as area under the time concentration curve (AUC), was increased significantly in doxorubicin resistant cells (156% increase) versus wild type MDA 231 cells (6% increase). Correction of the accumulation defect to doxorubicin in drug resistant cells required a 18–20 hour pre-incubation with toremifene. The effects of toremifene on cell cycle in MDA A-1 cells was analyzed by flow cytometric techniques. Toremifene had a dose response relationship in blocking cells in G0–G1 reducing the number of cells entering S phase of the cell cycle. This effect was maximal at concentrations which increased the accumulation of doxorubicin in MDA A-1 cells. Several metabolites of toremifene were also noted to increase doxorubicin accumulation in MDA A-1 doxorubicin resistant cells. Tore XVIII (deaminocarboxytoremifene), Tore IV (4-hydroxy-N-desmethyltoremifene) and N-desmethyltoremifene all increased the accumulation of doxorubicin significantly (114%, 128% and 42% respectively). Finally, we show evidence that toremifene and its active metabolites are present in high concentrations in human plasma following a single 200 mg oral dose. Toremifene remains a very promising agent for modulating doxorubicin cytotoxicity in multidrug resistance.
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  • 34
    ISSN: 1573-7217
    Keywords: neural networks ; breast cancer ; prognosis ; survival analysis ; Cox regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neural Network Analysis, a form of artificial intelligence, was successfully used to predict the clinical outcome of node-positive breast cancer patients. A Neural Network was trained to predict clinical outcome using prognostic information from 1008 patients. During training, the network received as input information tumor hormone receptor status, DNA index and S-phase determination by flow cytometry, tumor size, number of axillary lymph nodes involved with tumor, and age of the patient, as well as lengtl of clinical followup, relapse status, and time of relapse. The ability of the trained Network to determine relapse probability was then validated in a separate set of 960 patients. The Neural Network was as powerful as Cox Regression Modeling inidentifying breast cancer patients at high and low risk for relapse.
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  • 35
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen receptor ; prognosis ; prognostic factors ; pS2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary pS2 protein expression has been reported to have prognostic significance in human breast carcinomas and to correlate with estrogen receptor positivity, although these findings have not been confirmed by all investigators. pS2 positivity was compared to various clinical and histologic parameters in a retrospective study of 290 patients (median follow-up 7.2 years) and significantly correlated with tumor grade and estrogen receptor content (p=0.001 and p=0.0007, respectively). Significant associations between pS2 positivity and lymph node metastases, T stage, histologic tumor type, and patient age were not observed. Univariate and multivariate analyses (controlling for estrogen receptor content, T and N stage) of the patient population at large showed that pS2 positivity was not predictive of disease-free or overall survival. Univariate analysis of lymph node negative patients demonstrated that both pS2 and estrogen receptor positivity were significantly associated with a better outcome. Multivariate analysis of these patients, however, showed that only estrogen receptor data had independent prognostic significance. This study suggests that immunohistochemical analysis for pS2 protein expression will not contribute additional prognostic information if the estrogen receptor content is known.
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  • 36
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; doxorubicin ; mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Weekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18–67+ weeks), while 8 patients (29%) showed stable disease with a median duration of 28 weeks (range 11+–60 weeks). Gastrointestinal toxicity and alopecia were mild. Grade II and III leukopenia occurred in 63% of the courses without serious infectious disease. Four patients experienced an asymptomatic drop of 16–20% in the left ventricular ejection fraction (LVEF) after relatively low cumulative doses of each drug, and one patient with a history of pericarditis carcinomatosa and mediastinal irradiation developed a heart failure. In conclusion, this second-line combination treatment had moderate activity in breast cancer and caused only few subjective side effects, especially with respect to gastrointestinal symptoms.
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  • 37
    ISSN: 1573-7217
    Keywords: breast cancer ; conservation treatment ; local excision ; mastectomy ; radiotherapy ; rehabilitation ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared. To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity edema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (p2〈0.0001 and p2=0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2=0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2=0.085) at 1 year and (p2=0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome. These differences may be important to individuals and be significant in helping them choose between MRM and XRT based upon individual functional needs.
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  • 38
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    Breast cancer research and treatment 21 (1992), S. 155-164 
    ISSN: 1573-7217
    Keywords: breast cancer ; clinical trials ; ductal carcinoma in-situ ; lobular carcinoma in-situ ; tumor biology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-invasive breast cancer is comprised of two distinct entities: lobular carcinoma in-situ (LCIS) and ductal carcinoma in-situ (DCIS). The natural history of each clinical entity is described and a biologic interpretation of the available data is offered. Lobular carcinoma in-situ is considered only a risk marker rather than a precursor for the subsequent development of invasive cancer, so that once the diagnosis is established, further operative intervention is unnecessary and serial follow-up alone is recommended. The treatment of ductal carcinoma in-situ must take into account that breast-preserving therapy is now considered optimal treatment of invasive cancer of the breast, the disease we are trying to prevent. The pitfalls of recommending treatment based on retrospective data is emphasized and the need to support clinical trials designed to determine the optimal therapeutic management of intraductal carcinoma is affirmed.
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  • 39
    ISSN: 1573-7217
    Keywords: breast cancer ; site of first metastasis ; survival ; nodal status ; estrogen receptors ; progesterone receptors ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Survival from the detection of first metastasis (SAM) was analyzed in a single center series of 258 patients with advanced breast cancer. During the 15 year period covered by this study 230 patients died, 215 of their disease. The overall median SAM was 28 months. Univariate analysis of SAM stratified by first dominant site of metastasis, estrogen receptor status (ER), progesterone receptor status (PgR), tumor size, axillary lymph node status, patient age, menopausal status, and disease-free interval (DFI) showed the first dominant site of metastasis, ER, PgR, and axillary lymph node status to be significantly associated with SAM. Patients with visceral metastasis as first dominant site of metastasis had significantly shorter survival than those with either bone or soft tissue metastasis, median SAM 16 vs. 34 vs. 41 months respectively (P〈0.001). SAM also differed according to the steroid hormone receptor status of the primary tumor: median SAM 34 and 33 months for patients with ER-positive or patients with PgR-positive tumors against 14 months for patients with ER-negative or with PgR-negative tumors (P〈0.001). Patients with axillary lymph node involvement at primary disease had a shorter SAM than those without, median SAM 24 vs. 35 months (P=0.006). No association between SAM and either tumor size, patient age, menopausal status, or DFI could be observed. Multivariate analysis including first dominant site of metastasis, ER, PgR, and axillary lymph node status showed the first dominant site of metastasis, ER, and axillary lymph node status to be independently associated with SAM.
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  • 40
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    Breast cancer research and treatment 22 (1992), S. 59-67 
    ISSN: 1573-7217
    Keywords: benign breast disease ; breast cancer ; IGF receptors ; insulin-like growth factors ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The first step of the action of IGF1 and IGF2 (IGFs) is their binding to membrane receptors. IGF binding sites have been characterized by competitive binding and cross-linking techniques in human breast cancer cell lines as well as in human breast cancers and in human benign breast diseases. IGF2 is a good competitor of125I-IGF1 binding to IGF1-R; insulin competes but with a potency 1/100 lower than the IGF1 potency. Chemical cross-linking experiments revealed that the apparent molecular weight of the IGF1-binding sites is 130,000. Alpha IR-3, a murine monoclonal antibody against the IGF1-R, blocks IGF1-binding to this receptor. This antibody inhibits the IGF1-stimulated growth of breast cancer cells. Therefore, the IGF1 specific binding sites correspond to the previously described type 1 IGF receptors (IGF1-R) in normal tissues. Cross-linking experiments with labeled IGF2 resulted in a major band of apparent Mr 260,000–270,000 that was inhibited by unlabeled IGF2 but not by insulin, and corresponds to the type 2 IGF receptor; a second band of apparent Mr 130,000 was inhibited by excess IGFs and insulin (Type I receptor). The alpha-IR3 inhibition of the IGF2 mitogenic activity suggest that IGF1-R partially mediates the growth effect of IGF2 in these cells. We and others have demonstrated that most breast cancer cell lines contain IGF1-R. This is also the case in breast cancer biopsies in which histo-autoradiographic analyses allowed the localization of IGF1-R on the epithelial component. IGF1-R concentrations were positively correlated to estradiol and progesterone receptor concentrations. In our experience, the presence of IGF1-R is associated with a better prognosis. Finally, IGF1-R are found less frequently and at lower concentrations in benign breast diseases. These results suggest that IGF1-R could be a marker of the proliferative epithelial component within the tumor.
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  • 41
    ISSN: 1573-7217
    Keywords: breast cancer ; clinical trials ; Cox regression model ; generalized additive model ; non-linear prognostic factor modelling ; proportional hazards ; regression splines ; smoothing splines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The proportional hazards model is frequently used in analyzing the results of clinical trials, when it is often the case that the outcomes are right-censored. This model allows one to measure treatment effects and simultaneously identify and adjust for prognostic factors that might influence the outcome. In this paper, we outline a class of semiparametric models that allows one to model prognostic factors nonlinearly, and have the data suggest the form of their effect. The methods are illustrated in an analysis of data from a breast cancer clinical trial.
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  • 42
    ISSN: 1573-7217
    Keywords: artificial intelligence ; breast cancer ; neural networks ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been previously shown that Neural Networks can be trained to recognize individual breast cancer patients at high and low risk for recurrent disease and death. This paper expands on the initial investigation and shows that by coding time as one of the prognostic variables, a Neural Network can use censored survival data to predict patient outcome over time. In this demonstration a Neural Network was trained, tested, and validated using censored survival data from a group of 1373 patients with node-positive breast cancer. The Neural Network method predicted patient outcome as accurately as Cox Regression modeling. The final Neural Network model can be presented with a patient's prognostic information and make a series of predictions about probability of relapse at different times of follow-up, allowing one to draw survival probability curves for individual patients.
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  • 43
    ISSN: 1573-7217
    Keywords: breast cancer ; prognostic factors ; Cox regression ; all-subset regression ; accelerated failure time models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical studies usually employ Cox step-wise regression for multivariate investigations of prognostic factors. However, commercial packages now allow the consideration of accelerated failure time models (exponential, Weibull, log logistic, and log normal), if the underlying Cox assumption of proportional hazards is inappropriate. All-subset regressions are feasible for all these models. We studied a group of 378 node positive primary breast cancer patients accrued at the Henrietta Banting Breast Centre of Women's College Hospital, University of Toronto, between January 1, 1977, and December 31, 1986. 85% of these patients had complete prognostic factor data for multivariate analysis, and 96% of the patients were followed to 1990. There was evidence of marked departures from the proportional hazards assumption with two prognostic factors, number of positive nodes and adjuvant systemic therapy. The data strongly supported the log normal model. The all-subset regressions indicated that three models were similarly good. The variables 1) number of positive nodes, 2) tumour size, and 3) adjuvant systemic therapy were included in all three models along with one of three biochemical receptor variables 1) ER, 2) combined receptor (ER- PgR-; ER+ PgR-; ER- PgR+; ER+ PgR+; or 3) PgR. Better multivariate modeling was achieved by using quantitative prognostic factors, a check for appropriate underlying model-type, and all-subset variable selection. All-subset regressions should be considered for routine use with the many new prognostic factors currently under evaluation; it is very possible that there may not be a single model that is substantially better than others with the same number of variables.
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  • 44
    ISSN: 1573-7217
    Keywords: amplification ; c-erb-B2 ; PCR ; fine-needle biopsies ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aspiration of tumor cells by the fine-needle biopsy method yields only a small number of cells, which hampers conventional molecular analysis for the presence of multiple copies of oncogenes. We have therefore adopted the polymerase chain reaction (PCR) method to study semi-quantitatively the level of the c-erb-B2 gene in human breast tumor samples. Of 39 patients with mammary carcinoma, 7 (19%) contained multiple copies of c-erb-B2 genes, whereas only two samples failed to give informative data. Next the temporal appearance of multiple gene copies was examined in 20 patients with clinical stage IV disease. Tumor samples were obtained every second to third month from the same tumor lesion of each patient. None of the initial samples from each patient contained multiple copies of c-erb-B2. Of 16 patients that showed progressive clinical disease, 5 developed multiple gene copies, showing that the event occurs in clinical stage IV disease.
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  • 45
    ISSN: 1573-7217
    Keywords: breast cancer ; in situ hybridization ; interphase cytogenetics ; paraffin-embedded sections ; multistep carcinogenesis ; tumor cytogenetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fluorescentin situ hybridization techniques have provided an important tool for interphase cytogenetic studies of human neoplasms. However, these techniques are difficult to use on formalin-fixed archival tissue sections. We describe here a non-fluorescent, non-isotopicin situ hybridization (ISH) approach that is easily applicable to paraffin-embedded breast tissue sections. The technical steps that must be monitored and individualized to optimize signal generation and detection are discussed. This ISH technique has several advantages over fluorescent detection methods. The signal obtained can be viewed using an ordinary light microscope and does not fade with time. More importantly, the signal is observed and analyzed in the context of tissue morphology. The technique permits detection of numerical chromosomal abnormalities not only in malignant but also in apparently normal and potentially premalignant mammary tissue. This may allow identification of focal genetic abnormalities as well as field-defects and enable analysis of their evolution during the multistep transformation to mammary neoplasm. This technique is also suitable for analysis of tumor heterogeneity and the correlation of numerical chromosomal aberrations with histologic, immunocytochemical, and clinical features of breast tumors.
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  • 46
    ISSN: 1573-7217
    Keywords: breast cancer ; hepatitis B vaccination ; immune competence ; impaired immune response ; radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The response to hepatitis B (HBV) vaccination was studied in 32 breast cancer patients who were HBV antigen- and antibody-negative at the time of diagnosis. Ten of the patients included into the study received radical mastectomy without adjuvant therapy, 15 patients underwent breast-conserving surgery with subsequent irradiation with or without tamoxifen treatment, and 7 patients were treated by modified radical mastectomy plus adjuvant chemotherapy. Eight patients received the first dose of vaccine 3 months after irradiation therapy. Seven patients were first vaccinated 6 months following irradiation therapy. Seven healthy age-matched persons were vaccinated as controls. Antibody response in the patients was significantly delayed. Four weeks after the second vaccination 6 out of 7 controls showed a significant (〉10IU/ml) HBs antibody titer, while only 6 out of 32 patients responded. In addition, HBs antibody titers were also significantly lower after the second vaccination even in those patients treated with surgery alone, although they were first vaccinated 3 months after surgery and had no residual tumors. This difference disappeared after the second booster immunization, at which time the frequency of significant antibody titers and the levels of HBs antibody titers were comparable between patients and controls. As the population of patients undergoing treatment for breast cancer is increasing, additional studies are needed to determine optimal immunization regimens in this group of patients.
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  • 47
    ISSN: 1573-7217
    Keywords: breast cancer ; screening ; interval cancer ; overall survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to analyse the survival rate in a group of breast cancers detected in the intervals between screening examinations in relation to clinically detected cancers in a non-screened population. All interval and control cancers were recruited from a randomized controlled mammography screening trial in Stockholm. The overall survival up to eight years of observation was higher in 191 patients with interval cancers than in 142 control cancers (p=0.01). There were no significant differences between the two groups with regard to tumor size, stage distribution, or mean age, though the interval group did have a larger proportion of younger women. The similarity was confirmed by multiple regression analysis. The overall survival stage by stage was consistently higher in interval cancers. The survival rate in the true interval cancers was similar to that for those found in retrospect to have been detectable or traceable at the time of screening. No correlation was found between the length of the interval and the survival of patients with interval cancers. These results contradict the hypothesis that a high growth rate is associated with a poorer prognosis and that interval cancers are a more aggressive form of breast neoplasia.
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  • 48
    ISSN: 1573-7217
    Keywords: breast cancer ; LH-RH binding sites ; targeted chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The binding characteristics of several cytotoxic analogs of luteinizing hormone-releasing hormone (LH-RH) developed in our laboratory were examined in membranes from human breast cancer and estrogen independent MXT mammary cancer. Specific binding of [125I]D-Trp6-LH-RH and the cytotoxic LH-RH analog [125I]T-98 ([D-Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (HMAQG) was demonstrated in membrane preparations from human breast and MXT mammary tumor cells. Ligand binding of T-98 was specific, saturable, and dependent on temperature, time, and plasma membrane concentration. Analysis of the binding data showed that in human breast cancer, interaction of [125I]T-98 was consistent with the presence of two classes of LH-RH receptors, one class showing high affinity and low capacity, and the other class showing low affinity and high capacity binding. In membranes from MXT mammary cancer, T-98 bound to one class of saturable, specific, noncooperative binding sites with high affinity and low capacity. The rates of association and dissociation for [125I]T-98 were calculated to be 4.757×108 M−1 min−1 and 0.016 min−1 (t1/2=38.7) in membranes from MXT mammary cancer. In human breast cancer, association rate constants (K1a and K1b) were 2.3×106 M−1 min−1 for binding to high affinity and 1.8×104 M−1 min−1 for binding to low affinity binding sites. Dissociation rate constants were K−1a=0.0801 min−1 (t1/2a=63.4 min) and K−1b=0.0467 min−1 (t1/2b=23.5 min), respectively. [125I]T-98 was not displaced by either unlabeled somatostatin or epidermal growth factor, but was displaced completely by unlabeled T-98 or [D-Trp6]LH-RH. The analysis of displacement curves of [D-Trp6]LH-RH by cytotoxic agonists and antagonists of LH-RH synthesized in our laboratory showed that T-121, AJ-11, T-120, T-133, and T-98 were the most potent in displacing [125I]D-Trp6-LH-RH from breast and MXT cancer membranes. Binding kinetics and analyses of displacement curves of [125I]D-Trp6-LH-RH and [125I]T-98 in membranes of human breast cancer and estrogen independent MXT mouse mammary cancer suggest that binding of the cytotoxic analog T-98 to the LH-RH receptor proceeds reversibly like that of its congeners without cytotoxic radicals. Our findings may provide a stimulus for further studies with LH-RH analogs carrying cytotoxic radicals. Such analogs could be targeted to breast cancer and other cancers that have membrane receptors for LH-RH. Because the antitumor action may be exerted to a greater degree at more selective sites that have the cell membrane receptors, the peripheral toxicity could be reduced.
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  • 49
    ISSN: 1573-7233
    Keywords: prostacyclin ; thromboxane A2 ; 6-keto-PGF1α ; 2,3-dinor-6-keto-PGF1α ; 2,3-dinor-TXB2 ; nafazatrom ; breast cancer ; ovarian cancer ; cervix cancer ; leiomyonas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies investigating the role of thromboxane A2 and prostacyclin in cancer of the female breast and genital tract are reviewed. Whereas thromboxane A2 was found to promote the tumour growth and metastasis, prostacyclin exerted a protective effect in maintaining vascular and platelet homeostasis. Thus, monitoring of prostacyclin and thromboxane levels in plasma and urine of cancer patients may be essential for the evaluation of tumour growth and metastasis. Of all modulators of thromboxane and prostacyclin biosynthesis, nafazatrom was found to exhibit promising results for the treatment of advanced breast cancer, although its use in the routine therapy is questionable at this stage.
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  • 50
    ISSN: 1573-7276
    Keywords: axillary metastases ; breast cancer ; metastatic spiral ; periodicity ; quantitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The clinical value of assessment of tumour load in the axilla in the treatment of breast cancer patients has stood the test of time. Much information is available on its extent and characteristic distribution but, in contrast, little is known of the biological factors that may control the timing of the metastatic phenomenon. There is recent circumstantial evidence that such factors may exist and this prompted the present detailed study of axillary metastases from a series of 437 consecutive cases of breast carcinoma. Evidence of such factors was found here also: the excess of micrometastases in cases coming to operation in the second half of the year was highly significant (P 〈 0.001) and is consistent with a synchronized start to the metastatic process. The total metastatic pattern in the material further indicated that the process may show periods of inactivity, i.e. periods when new colonies are not recruited. Mechanisms controlling this periodicity could theoretically be light-mediated, opening up new possibilities in the development of anti-metastatic treatment regimes.
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  • 51
    ISSN: 1573-3521
    Keywords: cancer ; breast cancer ; information seeking ; evaluation ; communication channels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract This study examined women's evaluations of communication channels which are major carriers of cancer-related information. A sample of women over 40 (n=395) was asked which channels they had received cancer-related information from within the last year and what their evaluations were of these channels in terms of three dimensions: editorial tone (credibility), communication potential (presentation and style), and utility. Various statistical analyses revealed significant interactions between evaluations and channels and significant main effects for channels and for evaluations. Additional post hoc comparisons suggested that there was a general trend across channel characteristics to rate doctors and organizations more highly than friends/family and the media for providing cancer-related information, although the respondents did not perceive information received from doctors and organizations as more understandable or more novel than information obtained from the media. On the whole, friends and family were evaluated least positively. These results are discussed in terms of their relationship to other programmatic research in this area and their pragmatic implications for future cancer control efforts.
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  • 52
    ISSN: 1573-3599
    Keywords: breast cancer ; risk, genetics ; epidemiology ; family history
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Breast Cancer Risk Analysis, a service for women with breast cancer and their families, makes use of information drawn from fields such as genetics, epidemiology, and counseling. Its aim is to provide individuals with background information and information regarding the etiology and risks of breast cancer. Based on this information, individuals are helped to make appropriate decisions pertaining to treatment and follow-up. While making use of some of the information and processes used in genetic counseling, Breast Cancer Risk Analysis differs from most types of genetic counseling for reproductive decisions. Some of these differences are discussed here.
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  • 53
    ISSN: 1436-2813
    Keywords: prognostic factor ; lymph node metastases ; DNA-ploidy status ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the relationship between the regional lymph node metastases and the DNA ploidy status in 207 patients with invasive breast cancer, as well as their prognostic values in estimating the prognosis of breast cancer. A significantly higher incidence of aneuploidy was found in patients with a large T3 or T4 tumor, a positive axillary lymph node status, more than 4 positive axillary lymph nodes or positive internal mammary lymph nodes. In a univariate study, the overall survival was significantly correlated with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases, and DNA ploidy status. In the multivariate analysis, however, only axillary and internal mammary lymph node metastases were recognized as important independent prognostic factors on survival. In this series, the DNA ploidy status did not appear to be an independent prognostic factor either in the entire series or in negative axillary node patients, since it was closely correlated with the axillary or internal mammary lymph node metastases, and the axillary node negative patients had an extremely favorable prognosis.
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  • 54
    ISSN: 1436-2813
    Keywords: breast cancer ; estrogen receptor ; DNA ; ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relationship of estrogen receptor(ER) status to DNA ploidy was investigated in 121 patients with breast cancer who underwent surgery. Lymph node status was evaluated histologically and ER levels were determined by the dextran-coated charcoal method, with a level of 3 fmol/mg·protein being considered positive. Flow cytometric DNA content was analyzed using paraffin-embedded tissue blocks. Sixty-three per cent of the specimens were ER+, while 37 per cent were negative. Sixty-one patients (50.4 per cent) were diploid and 60 aneuploid. A statistically significant correlation between the ER positivity rate and diploid DNA was found. Higher ER levels were seen in the postmenopausal patients with diploid tumors than in those with aneuploid tumors and there was a significant tendency for ER levels to be higher in the diploid tumors. Nodal status was not correlated with ER positivity or ploidy pattern. The present results indicate that ER levels are correlated with DNA ploidy, and reflect the degree of functional differentiation.
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  • 55
    ISSN: 1436-2813
    Keywords: breast cancer ; parasternal lymph node ; extended radical mastectomy ; postoperative irradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to establish a therapeutic approach for primary breast cancer of medial and central origin, we reviewed 183 patients who had been treated by one of the following three modalities at the Second Department of Surgery, Osaka University Medical School between January, 1965 and December, 1980. Group A (n=70): standard radical mastectomy alone; Group B (n=34): standard radical mastectomy followed by postoperative irradiation to the parasternal and supraclavicular regions, and; Group C (n=62): extended radical mastectomy that included removal of the parasternal lymph nodes. The background factors of the three groups were not significantly different. The overall survival five and ten years following surgery in the three groups were 91 per cent and 79 per cent in group A, 82 per cent and 67 per cent in group B, and 82 per cent and 70 per cent in group C, respectively, showing no significant difference in overall survival among the three groups. When the patients were classified according to the extent of axillary lymph node involvement, there was no difference in survival among the three treatments in patients who had less than three lymph node metastases in the axilla. However, treatment of the parasternal lymph nodes improved survival in the patients who had more than four lymph node metastases in the axilla. Parasternal lymph node involvement definitely worsened the prognosis, showing it to be a good prognostic factor. Thus, extended radical mastectomy should be considered for patients with breast cancer of medial or central location, when extended axillary lymph node involvement is found.
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