Clinicopathological characteristics of breast carcinomas with allelic loss in the p73

p73, a new member of the p53 family, has been mapped to chromosome 1p36, a region where loss of heterozygosity (LOH) is frequently observed in primary human tumors. Allelic loss studies involving the 1parm in breast carcinomas offer rates ranging from 13% to 75%, depending on the genetic interval being studied. We investigated LOH in an intragenic microsatellite marker, and those centromerically flanking the p73 gene, at 1p36, and their correlations with patient age and 10 pathologic parameters in a series of 193 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using five markers of the 1p36 region (p73P1, D1S2694, D1S214, D1S2666 and D1S450). LOH was found in at least one of these markers in 27% of tumors. When we established the comparison between tumors with and without LOH and the distribution of the 10 pathologic parameters considered, we observed statistically significant differences in association with higher histologic grade (p=0.02), more advanced pathological stage (p=0.02), peritumoral vessel involvement (p=0.04) and poorly differentiated carcinomas (p=0.01), as well as in tumors that concomitantly exhibited lymph node metastases, peritumoral vessel involvement and absence of steroid receptors (p=0.02). These data suggest that LOH in the p73 region could be pathogenically related to breast cancer and possibly to a poor tumor prognosis.     

Impact of videotaped information on frequency and confidence of breast self-examination

Background Videotaped education materials to teach breast self-examination (BSE) are used worldwide. However, evaluation of videotaped BSE instructions is lacking. Methods Premenopausal women (mean age 33.4±11.2 years) without history of breast cancer were approached to participate in this experimental study and randomly assigned to a video intervention group (VG; n=130; length of the video=15 min) or non-video comparison group (NVG; n=121). All participants answered a questionnaire on BSE behavior and health beliefs. No additional training was given. The total duration of the session including completion of the questionnaire was 15min for the NVG and 30min for the VG. Three months later, changes in BSE behavior were compared in the two groups. The influence of health beliefs on actual BSE behavior was investigated as well. Results Women of both the VG and NVG performed BSE significantly more frequently at follow-up than at baseline. Analysis of covariance, using the baseline BSE-frequency as co-variate and the follow-up BSE frequency as the dependent variable, revealed that women in the VG (adjusted mean=7.9 times per year, 95%CI=6.5–9.4) performed BSE more frequently than women of the NVG (adjusted mean=6.1 times per year, 95%CI=4.6–7.5) (F=4.2, df=2, p=0.02). Among motivational predictors, having an example of a role model (modeling) was shown by regression analysis to explain the greatest amount of variance (13%) in BSE frequency. Conclusion Use of an educational videotape increased the frequency of BSE among premenopausal women.     

Hair product use and the risk of breast cancer in young women

Objectives: The reported mutagenic and carcinogenic effects of some chemicals present in hair dyes have raised concern that hair dye use could increase breast cancer risk. This case–control study evaluated how detailed aspects of hair coloring and hair spray application by reproductive-age women may affect breast cancer risk.Methods: Cases were white female residents of three counties of western Washington state 45 years of age or less, who were diagnosed with breast cancer between 1983 and 1990 (n=844). A sample of similarly aged women residing in the same counties served as controls (n=960). Information on hair coloring and hair spray use, as well as other exposures, was ascertained during in-person interviews.Results: Breast cancer cases were slightly more likely than controls to report ever having used some type of hair coloring application, including use of rinses, semi-permanent or permanent dyes, as well as bleaching then dyeing or frosting their hair (relative risk [RR]=1.3, 95% CI=1.0–1.6, adjusted for age, fullterm pregnancies, family history of breast cancer, and weight). In subgroup analyses, women with exclusive use of just one of these methods of hair coloring application had no elevation in risk (similarly adjusted RR=1.1, 95% CI=0.9–1.3), whereas women who used two or more of these methods did have an elevated risk (RR=1.9, 95% CI=1.4–2.5). Hair spray use was not related to the risk of breast cancer (ever versus never users: RR=1.0, 95% CI=0.8–1.3).Conclusion: The lack of an association between exclusive use of a single type of hair coloring application and breast cancer risk argues that hair coloring application does not influence breast cancer risk among reproductive-age women. Thus, the results of the present study, as well as negative ones from most (but not all) prior studies, are most consistent with the conclusion that neither hair coloring application nor hair spray application influences breast cancer risk.     

Low body mass index is an independent predictive factor of local recurrence after conservative treatment for breast cancer

Background. Obesity or increased body mass index (BMI) has been shown to have two important adverse effects related to breast cancer. First, several studies have identified an association between increased BMI and advanced stage breast cancer. Second, increased BMI has been shown to be associated with poorer prognosis. In a previous report, we had identified low BMI as a risk factor for local reccurence at five years. The objectives of this study were to evaluate the relationship between BMI and local control and to confirm this prognostic factor in a larger population with an important follow-up. Materials and methods. Between 1976 and 1988, 605 women with invasive breast carcinoma less than 4cm in diameter underwent conservative surgery with axillary dissection and radiation therapy. The median follow-up time was 82 months. The risk of local recurrence and distant metastasis was evaluated by univariate retrospective analysis using Kaplan–Meier method for the main clinical and histologic factors. Those found to be significant were entered in a Cox model for multivariate analysis. Results. Since the beginning of the study, 80 patients had developed local recurrence. The 5 years and 10 years local control rates were 91% and 83%, respectively. Four parameters were independent predictive factors of local recurrence: Age lower than 40 years (HR=2.42 95% CI=[1.35–4.34]), BMI: elevation of one unit reducing the local recurrence of 0.92 95%CI=[0.85–0.99], multifocality of the tumor on pathological examination (HR=2.12 95% CI=[1.16–3.88]) and positive axillary nodes HR=0.54 95% CI=[0.31–0.95]. Size of the breast was not a predictive factor for local cancer recurrence. Low BMI did not increase risk of distant. Conclusion. Our study offers new data concerning the possibility that thinness may be related to local recurrence of breast cancer.     

Flow cytometric analysis of primary tumors and their corresponding metastatic nodes in breast cancer

Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from one which is indolent to one which rapidly progresses. Although it is the metastasis rather than the primary tumor that ultimately overwhelms the patients, studies concerning the DNA pattern have focused on the primary tumors. This study was undertaken to identify heterogeneities between primary tumors and metastases, and to evaluate the prognostic significance of the ploidy pattern and the S-phase fraction (SPF) of metastatic nodes in axillary node positive patients. Seventy-four frozen specimens of the primary and corresponding metastatic nodes from 37 patients have been analyzed by flow cytometry and the SPF calculated. The results of ploidy pattern analysis in primaries revealed 25 diploidy (67.6%) and 12 aneuploidy (32.4%), while those in metastasis showed 17 diploidy (46.0%) and 20 aneuploidy (54.0%). The aneuploidy group in metastatic nodes had the poorer histological grade (85.0% vs. 15.0%, p=0.02), and more mean metastatic nodes (5.75±2.10 vs. 3.05±1.56, p=0.018), and more frequent lymphatic vessel invasion (65.0% vs. 11.8%, p=0.031) than its counterpart. Decreased expression of ER (70.6% vs. 25.0% p=0.006) and increased expression of c-erbB2 (65.0% vs. 23.5%, p=0.012) were observed in the aneuploidy of metastatic nodes. The group with higher SPF in metastatic nodes had more metastatic nodes (5.47±2.31 vs. 4.00±1.78, p=0.042), and the higher incidence of lymphatic vessel invasion (57.9% vs. 22.2%, p=0.027), and poor histological grade (71.4% vs. 37.5%, p=0.039). In conclusion, the cell populations in metastatic nodes revealed DNA pattern which differed from that of primary tumors. The ploidy pattern and SPF in metastatic nodes might be considered as discriminate measure for risk factors in breast cancer patients with positive axillary node.     

Relationship between the morphological and biological characteristics of intraductal components accompanying invasive ductal breast carcinoma and patient age

We divided 324 cases with invasive ductal breast carcinoma into three age groups, and investigated the differences in proliferative activity and extension of the intraductal components among the age cohorts. Proliferative activity was expressed as the number of MIB1-positive nuclei per 1000 cancer cells in the intraductal components (MLI), and the intraductal component extension farthest from the invasive focus was defined as the maximum distance of ductal spread (MXDS). Moreover, analyses were conducted for three grade types, classified according to the classification system of ductal carcinoma in situ. The under-40 age group had significantly higher MXDS values than the other two age groups (p=0.0280), and this trend was more marked in those with the non-high grade without necrosis type (p=0.0045). The under-40 age group had higher MLIs, but the differences did not reach statistical significance (p=0.0793). In regard to those with the high grade type, the under-40 age group had significantly higher MLIs than the other two age groups (p=0.0269), and this trend was not significant in the cases with any other grade types. Associations between the age group and the margin status of the lumpectomy specimens were investigated in the 143 cases in which breast conserving surgery was tried. The under-40s had a significantly higher margin-positive rate in their lumpectomy specimens than the other two age groups (p=0.0362), and this trend was also seen in the groups with the non-high grade without necrosis type (p=0.0256). These results confirm the importance of considering patient age when designing surgical procedures for breast conserving therapy.     

Inflammatory Breast Cancer Survival: The Role of Obesity and Menopausal Status at Diagnosis

No previous studies have evaluated the effect of body size and menopausal status at diagnosis on survival from inflammatory breast cancer (IBC). We evaluated whether obesity and menopausal status had an impact on IBC survival in a cohort of 177 female IBC patients seen from 1974 to 1993 at The University of Texas MD Anderson Cancer Center. Survival time was defined as time from diagnosis until death or censorship at last date of contact. We categorized women by body size by using the National Institutes of Health/National Heart, Lung, and Blood Institute's definitions of obesity as body mass index ((BMI)=weight in kg/(height in m)²)30, overweight as 25BMI <30kg/m², and normal/lean as BMI <25kg/m². Cox proportional hazards analysis, adjusting for axillary lymph node involvement and chemotherapy protocol, revealed a modifying effect of menopausal status at diagnosis on the association between obesity and IBC survival (P=0.02). Relative to postmenopausal women, premenopausal women had significantly worse survival (hazard ratio (HR)=1.51, 95% confidence interval (CI)=1.03–2.22). After stratifying by menopausal status, premenopausal obese women had non-significantly better survival than their leaner premenopausal counterparts (HR=0.63, 95% CI=0.34–1.15) while postmenopausal obese women had significantly worse survival than their leaner counterparts (HR=1.86, 95% CI=1.02–3.40). These findings suggest that factors associated with larger body size at diagnosis may contribute to shorter IBC survival among postmenopausal women but not premenopausal women, who were found to have poorer survival regardless of body size.     

Effect of the aromatase inhibitor vorozole on estrogen and progesterone receptor content of rat mammary carcinomas induced by 1-methyl-1-nitrosourea

Vorozole, a nonsteroidal aromatase inhibitor, impedes the post-initiation stage of chemically induced mammary carcinogenesis. While various aspects of vorozole's effects on mammary carcinoma development have been investigated, little attention has been directed to determining the estrogen receptor (ER) and progesterone receptor (PR) content of mammary carcinomas that arise despite vorozole treatment. Female Sprague–Dawley rats were given an i.p. injection of 50mg MNU/kg body weight at 21 days of age and placed on diet supplemented with 0 or 3mg vorozole/kg, which had no effect on mammary tumor development. Histologically confirmed carcinomas were evaluated for ER and PR by immunohistochemistry. In the control group, 78.8% of carcinomas were ER positive with an ER content ranging from 13.8 to 40.0%, similar to ER content of mammary ductal epithelial cells from non-carcinogen treated animals. PR content ranged from 4.4 to 45.2% and also was similar to levels of PR observed in ductal epithelial cells. ER was not correlated with PR in mammary carcinomas (r=0.05, p>0.80), whereas there was a significant correlation in ductal epithelium (r=0.86, p=0.006). In vorozole-treated rats, no ER negative carcinomas were observed and overall ER expression by vorozole was elevated (p<0.03). All carcinomas from vorozole-treated rats expressed PR (2.5–60.2%) and correlation between ER and PR content was numerically greater in carcinomas from vorozole-treated animals (r=0.42, p=0.09). These data, which are considered hypothesis generating, provide evidence that low doses of vorozole in the diet select for mammary carcinomas with an increased ER positive phenotype.     

High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors

Current treatment for high risk and recurrent medulloblastoma (MB) and supratentorial primitive neuroectodermal tumors (stPNET) has a very poor prognosis in children. High dose chemotherapy (HDCT) and autologous stem cell rescue have improved survival rates. We present 19 patients (thirteen classified in the high risk group and six patients with recurrent disease) that received HDCT and autologous stem cell rescue.In the high risk group [Med Pediatr Oncol 38 (2002) 83], all patients underwent neurosurgical debulking. Standard chemotherapy was prescribed in 10 patients. Radiotherapy was given to 4 patients (all older than 4years old). In the recurrence disease group [Childs Nerv Syst 15 (1999) 498], five patients underwent surgery. Radiotherapy was given to those who were not previously irradiated. The HDCT in twelve patients consisted of busulfan 4mg/kg/day, orally over 4days in 6-hourly divided doses and melphalan at a dose of 140mg/m²/day by intravenous infusion over 5min on day –1. Three patients additionally received thiotepa 250mg/m²/day intravenously over 2days and four patients additionally received topotecan 2mg/m²/day over 5days by intravenous infusion over 30min. The other seven patients received busulfan and thiotepa at the same doses.Patients stem cells were mobilized with granulocyte colony-stimulating factor at a dose of 12g/kg twice daily subcutaneously for four consecutive days. Cryopreserved peripheral blood progenitor cells were re-infused 48h after completion of chemotherapy. With a median follow-up of 34months (range 5–93) eight complete responses and one partial response were observed. Three patients died of treatment-related toxicities (15%). The 2 year event-free survival was 37.67±14% in all patients and 57±15% for the high risk group.Therefore we conclude that HDCT may improve survival rates in patients with high risk/recurrent MB and stPNET despite treatment toxicity.     

p53 expression is decreased in primary breast carcinomas with microsatellite instability

p53 and p185 expression in primary breast cancer with microsatellite instability (MSI) is still largely unexplored. To investigate the relationship between these oncoproteins and the pathways of genomic instability, we examined 52 primary invasive breast cancers stratified by the presence and absence of MSI. We determined the status of eight microsatellite loci using radioactive and silver staining methods, and evaluated the immunohistochemical expression of p53 and p185 in a consecutive series of Italian cancer patients characterized by clinical-pathological and biological parameters. Nineteen cases (36.5%) were MSI-positive in at least two loci. p53 was expressed in 15 cases (28.8%) and p185 in eight (15.4%). MSI-positive tumors were inversely correlated with p53 expression (p=0.0007); in addition, the percent of p53-expressing cells decreased as the number of MSI-positive loci increased. MSI-positive tumors were correlated with a larger tumor size (p=0.04), lymph-node metastasis (p=0.001), and advanced clinical stage (p=0.0006). These data demonstrate the existence of two subsets of primary breast cancers: one characterized by MSI, the other by p53 expression. MSI-positive patients had a more advanced and/or aggressive disease.     

Progression of Premalignant MCF10AT Generates Heterogeneous Malignant Variants with Characteristic Histologic Types and Immunohistochemical Markers

The purpose of this study was to evaluate the pain experience of women during mammography for breast cancer screening. Possible associations with personal and medical history, sociodemographics and/or situational factors were studied. It was also investigated whether this pain influenced the intention to return for future breast cancer screening. In the Netherlands, women between 50–75 years are invited for screening every two years. A total of 1200 participants were asked to fill up a questionnaire. The response rate was 79.5% (n=954), and 945 questionnaires contained adequate information for analyses. A total of 689 women (72.9%) described mammography as mild to severely painful. In this group, compared to the group that reported no pain, the following factors occurred significantly more often: sensitive breasts (P=0.001), family history of breast diseases (P=0.017), expected pain based on former mammography (P=0.001), high education (P=0.008), anxiety (P=0.001), breast sensitivity in last three days (P=0.001), insufficient attention of technologist (P=0.001). Other factors like age, hormonal status, breast size and hormone use were not associated with the pain experienced. Thirty-two women (3.3%) indicated that they would not attend further screening, 25 (2.6%) reported that the pain might deter them, six women (0.6%) had other reasons, one woman (0.1%) was sure not to come because of severe pain. In conclusion, a large majority of women attending breast cancer screening describes mammography as painful (72.9%). Factors associated with pain were described. Relatively few women (2.7%) indicated that the pain might deter them from future mammography. Recommendations are given to reduce the pain experienced during screening mammography.     

Pharmacokinetics of Sodium Borocaptate: A Critical Assessment of Dosing Paradigms for Boron Neutron Capture Therapy

The pharmacokinetics of sodium borocaptate (BSH), a drug that has been used clinically for boron neutron capture therapy (BNCT) of malignant brain tumors, have been characterized by measuring boron concentrations by direct current plasma-atomic emission spectroscopy (DCP-AES) in a group of 23 patients with high-grade gliomas. The disposition of BSH following intravenous (i.v.) infusion, which was determined by measuring plasma boron concentrations by DCP-AES, was consistent with a three-compartment open model with zero-order input and first-order elimination from the central compartment. Boron disposition was linear over the dose range of 26.5–88.2mg BSH/kg body weight (b.w.), corresponding to 15–50mg boron/kg b.w. Mean total body boron plasma clearance was 14.4±3.5ml/min and the harmonic mean half-lives (range) were 0.6 (0.3–3.7), 6.5 (4.8–10.1) and 77.8 (49.6–172.0)h for the ,, and disposition phases, respectively. Using an empirically determined plasma:blood boron concentration ratio of 1.3±0.2, the calculated total body boron blood clearance was 18.5±4.5ml/min. In order to develop a model for selecting the optimum dosing paradigm, a pharmacokinetic correlation was established between the boron content of normal brain, solid tumor, and infiltrating tumor to the shallow tissue pharmacokinetic compartment (C₂). Based on our model, it was concluded that although multiple i.v. infusions of BSH might increase absolute tumor boron concentrations, they will not improve the tumor:plasma boron concentration ratios over those attainable by a single i.v. infusion. The results from our study are confirmatory of those previously reported by others when blood sampling has been carried out for a sufficient period of time to adequately characterize the pharmacokinetics.     

Effects of Amifostine on Cisplatin Induced DNA Adduct Formation and Toxicity in Malignant Glioma and Normal Tissues in Rat

The chemoprotective effect of amifostine (WR2721) was studied in a BDIX rat model with intracerebral BT4C glioma implants. Twenty-one rats were given cisplatin 5mg/kg i.p., 21 were given amifostine 200mg/kg i.p.+cisplatin 5mg/kg i.p. Ten rats served as untreated controls. An immunohistochemical method for analysis of cisplatin–DNA adducts was used to elucidate the adduct formation in tumor, normal brain and kidney. Tumor volume and serum creatinine level were analysed 10 days after treatment. In animals pretreated with amifostine there was a delayed adduct formation rate in the normal brain, and in the kidney cortex the number of tubular cells with extremely high adduct level was reduced. No difference in adduct formation was seen in tumors. Tumor volume was significantly larger following amifostine+cisplatin (66% of controls) compared to cisplatin alone (38% of controls). Weight loss was, however, severe in rats given cisplatin alone. In the tumor growth study only 3 out of 11 rats treated with cisplatin 5mg/kg alone survived until time of sacrifice at 10 days, whereas all those pretreated with amifostine survived. Mean serum creatinine was 48µmol/l (controls), 146µmol/l (cisplatin) and 59µmol/l (amifostine+cisplatin). A marked reduction of histopathological renal changes was found when amifostine was added. Amifostine thus significantly reduced general and renal toxicity of cisplatin. The tumor growth retardation was stronger when cisplatin was given alone but this is probably related to general toxicity and malnutrition indirectly supported by the fact that amifostine did not significantly reduce cisplatin–DNA adduct formation in tumors. The results of the present study suggest that amifostine may have a role in increasing the therapeutic ratio of cisplatin, also in the treatment of malignant glioma.     

High complete pathological response in locally advanced breast cancer using paclitaxel and cisplatin

Background.In an earlier study, we have demonstrated a high response rate in metastatic breast cancer using paclitaxel (P) and cisplatin (C). A phase II study using the same regimen (PC) has been conducted in locally advanced breast cancer (LABC). Methods.A total of 72 consecutive patients with non-inflammatory LABC (T24cm, T3 or T4, N0–N2, M0). Patients were scheduled to receive 3–4 cycles of the neoadjuvant PC (paclitaxel 135mg/m² and cisplatin 75mg/m² on day 1) every 21 days. Patients were then subjected to surgery and subsequently received 6 cycles of FAC (5-fluorouracil 500mg/m², doxorubicin 50mg/m², and cyclophosphamide 500mg/m²) or 4 cycles of AC (doxorubicin 60mg/m², and cyclophosphamide 600mg/m²). Patients then received radiation therapy, and those with hormone receptor positive tumors were given adjuvant tamoxifen intended for 5 years. Results.The median age was 39 years (range, 24–78). Clinically, 7%, 58%, and 35% of patients had T24cm, T3, and T4, respectively. Disease stage at diagnosis was IIB (33%), IIIA (27%), and IIIB (40%). Complete and partial clinical response to PC was demonstrated in 13 (18%), and 52 (72%) patients, respectively. Of those patients with evaluable pathologic response (68 patients), complete pathologic response (pCR) was achieved in 15 (22%) patients. At a median follow-up of 22 (±3.5) months, 58 (81%) were alive with no recurrence, nine (12%) were alive with evidence of disease, and five (7%) were dead. None of the patients achieving pCR has developed any relapse. The median overall survival has not been reached for all 72 patients with a projected 3-year survival (±SE) of 90% (±4%). The median progression-free survival (PFS) was 42.1 (±4.8) months with a projected PFS of 74%±7% at 3-years (for 68 patients). Conclusions.PC regimen in LABC produced a high pCR. The contribution of the other added modalities to survival could not be assessed.     

Weight gain in women with breast cancer treated with adjuvant cyclophosphomide,methotrexate and 5-fluorouracil. Analysis of resting energy expenditure and body composition

Background. Weight gain is a common side effect observed in women undergoing adjuvant chemotherapy for breast cancer. Among possible causes a direct effect of chemotherapy on metabolism has been proposed. Body composition variations after adjuvant chemotherapy suggest the occurrence of sarcopenic obesity, possibly due to ovarian failure. We investigated acute and chronic effects of adjuvant chemotherapy on body weight, resting energy expenditure (REE) and plasma catecholamines in a group of menopausal women. Patients and methods. Thirty menopausal women with stage I–II breast cancer were recruited for the study. We measured REE and respiratory quotient (RQ) and body composition at the beginning and after 3 and 6 months of adjuvant cyclophosphomide, methotrexate, and 5-fluorouracil (CMF). REE, RQ, and plasma catecholamines were assessed before and after each chemotherapy session. At each session food intake was also assessed in all patients, by a food diary. Seven patients out of the group of 30 were also evaluated after a placebo infusion (saline). Results. A significant weight gain was observed in all women (70.5±3 v.s. 67.7±3kg, p<0.001), with increase in both fat-free mass (FFM) (45.2±1.5 v.s. 43.6±1.3kg, p<0.001) and fat-mass (FM) (25.3±1.7 v.s. 24.1±1.8kg, p<0.005). A decrease in REE and RQ was observed both during CMF and placebo infusion (p<0.05). During acute CMF and placebo infusion a reduction of plasma levels of noradrenaline was observed at the first and last session. REE increased progressively during the study period. Conclusions. CMF therapy apparently has no effect on REE either acutely or during a 6-month-period; the increased REE observed in the long-term is likely due to the concomitant increase in FFM. The lack of evidence of sarcopenic obesity, at variance with previous literature, is likely due to different patient selection.     

Breast and Ovarian Cancer Screening Practices in Healthy Women with a Strong Family History of Breast or Ovarian Cancer

Studies in women with a family history of cancer demonstrate a wide variability in the uptake of cancer screening measures. Little data exist regarding the breast and ovarian cancer screening practices of women who are members of hereditary breast cancer families. In order to address this issue, we examined the screening behaviors and the determinants of screening in a clinic based group of 216 women with a strong family history of breast or ovarian cancer who were participating in a free genetic counseling and testing research program. At baseline, prior to obtaining genetic counseling or testing, 50% of women ages 30–39, 83% of those age 40–49, 69% of those 50–64, and 53% of those 65 reported having a mammogram in the prior year. Adherence to mammography recommendations was correlated with age, number of relatives with breast cancer, and income. Twenty percent of participants had at least one CA-125 performed and 31% had ever obtained a screening ultrasound. Having at least one relative with ovarian cancer was very strongly associated with ovarian cancer screening [OR=12.3, 95% CI=4.6–33 for CA-125; OR=4.9, 95% CI=2.4,10.1 for ultrasound]. No association between cancer worries/distress and either breast or ovarian cancer screening was found. In conclusion, the breast and ovarian screening uptake in healthy women from hereditary breast cancer families is suboptimal, even for women over age 50, for whom annual mammography is clearly indicated. These findings indicate a need for better education about screening guidelines for high-risk women.     

Suppression of Cell Invasion on Human Malignant Glioma Cell Lines by a Novel Matrix-metalloproteinase Inhibitor SI-27: In Vitro Study

Matrix metalloproteinase (MMP) has come to be highlighted by its close relation to the cell invasion of gliomas. Suppression of MMP activity in malignant glioma cells would be meriting to local delivery of genes or chemotherapeutic agents. In this study, we employed a novel MMP inhibitor, SI-27 to investigate inhibition of cell invasiveness in human malignant glioma cell lines, U87MG, U251MG, and U373MG. We evaluated with zymogram, reverse zymogram, and cell invasion assay after exposure of SI-27 for 24h followed by preliminary MTT assay to find non-cytotoxic dose range, 51050100g/ml compared with non-treatment group as the control. Common to three glioma cell lines, zymogram disclosed that expressions of MMP-2 and -9 were suppressed in a dose-dependent fashion, meanwhile those of tissue inhibitor of MMP (TIMMP) in reverse zymogram were not. The numbers of invading cells through Boyden chamber were significantly reduced in a dose-dependent manner, while those with 5g/ml were not diminished common to those three lines. In conclusion, dose concentration ranging 10–100g/ml of SI-27 inhibited MMP-2 and -9 mediated cell invasiveness in malignant glioma cell lines. This is the first report for chemotherapeutic effect of SI-27 on glioma cells.     

Accuracy of mammography and echography versus clinical palpation in the assessment of response to primary chemotherapy in breast cancer patients with operable disease

The response to primary chemotherapy is an important prognostic factor in patients with non metastatic breast cancer. In this study we compared the assessment of response performed by clinical palpation to that performed by echography and mammography in 141 out of 157 consecutive breast cancer patients (T2-4, N0-1, M0) submitted to primary chemotherapy. A low relationship was recorded between tumor size assessed clinically and that evaluated by either mammography: Spearman R=0.38 or echography: R=0.24, while a greater correlation was found between the tumor dimension obtained by the two imaging techniques (R=0.62). According to the WHO criteria, the grade of response of breast cancer to primary chemotherapy, showed by mammography and echography, was less marked than the grade of response seen at clinical examination. Residual tumor size assessed clinically depicted a stronger correlation with pathological findings (R=0.68) than the residual disease assessed by echography (R=0.29) and mammography (R=0.33). Post-chemotherapy histology evaluation revealed pathological complete response in three cases (2.1%). Two of these cases were judged as complete responders by clinical palpation but only one was recognized by mammography, and none by echography. Clinical response, but not the response obtained by the two imaging techniques, was a significant predictor for longer disease free survival (p=0.04). To conclude, physical examination measurements remain the method of choice in evaluating preoperatively the disease response in trials of primary chemotherapy. Prediction of pathological outcome is not improved by echography and mammography.     

Sociodemographic factors associated with prostatectomy utilization and concordance with the physician data query for prostate cancer (United States)

Objectives: Data from the California Cancer Registry were used to model the effect of race/ethnicity, census-derived socioeconomic status (SES), age, year, and stage at diagnosis on prostatectomy utilization in men diagnosed with prostate cancer from 1990 through 1993. Treatment received was compared with the National Cancer Institute's Physician Data Query (PDQ) to evaluate concordance.Methods: Odds ratios (OR) and 95% confidence intervals (CI) were estimated to assess the likelihood of (a) receiving a prostatectomy and (b) receiving a treatment in concordance with the PDQ. Non-concordance was defined as a prostatectomy performed on a patient who was either diagnosed with AJCC stage III or IV prostate cancer, or was older than 70 years. All other treatments were considered compliant with the PDQ.Results: Regardless of the stage at diagnosis, men who were younger and lived in a neighborhood with higher income and education levels were the most likely to receive a prostatectomy as opposed to other treatments. Black men were the least likely to be treated with prostatectomy (OR=0.6, CI=0.5–0.6), and the differential was evident within all income levels examined. With respect to the PDQ, black men were 1.4 times more likely to receive concordant treatment than white men (OR=1.4, CI=1.3–1.5).Conclusions: California black men are receiving less aggressive treatment (that is more concordant with the PDQ) when diagnosed with prostate cancer.     

Biomarkers for local recurrence after breast‐conservation — a nested case‐control study

Purpose: A previous cohort study of 759 women with invasive T1T2 breast cancer operated on with breastconserving surgery in Stockholm between 1976 and 1986 indicated that age <50 years, no postoperative irradiation, and nodal involvement were independent risk factors for ipsilateral breast tumor recurrences (IBTR). The aim of the current study was to analyse if selected biological markers assayed in tumor specimens from these patients could add prognostic information, thereby helping to identify groups of patients at high versus low risk of IBTR.Methods: The study was designed as a casecontrol study nested within the cohort. The cohort was stratified according to nodal status and the use of postoperative irradiation. In these four strata, the cases were those 80 women who developed IBTR between 1977 and 1994. In each stratum, women without IBTR were randomly selected as controls (n=159). Median time at risk was 12 (8–18) years. The following factors were analysed: histopathological tumor grade according to Elston–Ellis, DNA ploidy, immunohistochemical staining for apoptosis, angiogenesis, Ki67 (MIB1), cerbB2, p53, waf1, and bcl2. The prognostic role of each factor was assessed using linear logistic regression methods.Results: In univariate analyses only age <50 years was identified as a significant risk factor for IBTR, whereas none of the studied biomarkers yielded statistically significant information. However, in a multivariate model, age, MIB-1-index, and tumor grade significantly influenced the risk for IBTR: the odds-ratio (OR) for age 50 years was 0.4, 95% confidence interval (CI)=0.2–0.9; for medium or high grade tumors it was 0.4 (CI=09–0.9); and for MIB-1-index >30%, 2.1 (CI=1.0–4.4). In women 50 years, MIB-1-index >30% was associated with an OR of 3.5 (CI=1.4–8.8) compared to those who were younger. Patients 50 years with MIB-1-index 30% were thus identified as a low-risk group with an OR of 0.2 (CI=0.1–0.5). A possible high-risk group was patients <50 years with tumors showing a combination of c-erbB-2 and waf-1 immunoreactivity, with an OR of 6.7 (CI=1.3–34.7).Conclusion: Women 50 years with MIB-1-index 30% constituted a subgroup with a low risk of IBTR. This observation raises the issue whether this group of patients might be spared postoperative irradiation following breast-conserving surgery. However, due to the methodology of the study, including the large number of comparisions, the presented results warrant cautious interpretation and should be regarded as tentative.