Biomedical subjects

Peggy Porter

Publications and source records attributed to Peggy Porter.

11 recordsLinked to original sources

PubMed2007

Primary systemic chemotherapy of invasive lobular carcinoma of the breast.

Invasive lobular carcinoma is the second most frequent histological type of breast cancer and its incidence is increasing. It has unique clinical, biological, and molecular features. Invasive lobular carcinoma is almost invariably positive for the oestrogen receptor and, when compared with invasive ductal carcinoma, it is typically of a lower grade. Even though invasive lobular carcinoma represents a distinct clinical entity, the same criteria used for invasive ductal carcinoma are currently applied to establish the need for primary or adjuvant systemic chemotherapy. We reviewed randomised trials of neoadjuvant and adjuvant chemotherapy and noted that insufficient evidence is available to support or withhold use of chemotherapy in patients with invasive lobular carcinoma. Thus, the benefit from systemic chemotherapy for individuals with this form of breast disease is unclear. Invasive lobular carcinoma deserves to be investigated separately in prospective clinical trials to define the best treatment and prevention strategies.

Antineoplastic Agents↗

PubMed2006

Cytogenetic characterization and H-ras associated transformation of immortalized human mammary epithelial cells.

INTRODUCTION: Immortalization is a key step in malignant transformation, but immortalization alone is insufficient for transformation. Human mammary epithelial cell (HMEC) transformation is a complex process that requires additional genetic changes beyond immortalization and can be accomplished in vitro by accumulation of genetic changes and expression of H-ras. METHODS: HMEC were immortalized by serial passaging and transduction with the catalytic subunit of the human telomerase gene (hTERT). The immortalized cells were passaged in vitro and studied by a combination of G-banding and Spectral Karyotyping (SKY). H-ras transduced, hTERT immortalized cells were cloned in soft agar and injected into nude mice. Extensive analysis was performed on the tumors that developed in nude mice, including immunohistochemistry and western blotting. RESULTS: Immortal HMEC alone were not tumorigenic in gamma-irradiated nude mice and could not grow in soft agar. Late passage hTERT immortalized HMEC from a donor transduced with a retroviral vector containing the mutant, autoactive, human H-ras61L gene acquired anchorage independent growth properties and the capacity for tumorigenic growth in vivo. The tumors that developed in the nude mice were poorly differentiated epithelial carcinomas that continued to overexpress ras. These cells were resistant to doxorubicin mediated G1/S phase arrest but were sensitive to treatment with a farnesyltransferase inhibitor. CONCLUSION: Some of the cytogenetic changes are similar to what is observed in premalignant and malignant breast lesions. Despite these changes, late passage immortal HMEC are not tumorigenic and could only be transformed with overexpression of a mutant H-ras oncogene.

Journal Article↗

PubMed2005

Denoising array-based comparative genomic hybridization data using wavelets.

Array-based comparative genomic hybridization (array-CGH) provides a high-throughput, high-resolution method to measure relative changes in DNA copy number simultaneously at thousands of genomic loci. Typically, these measurements are reported and displayed linearly on chromosome maps, and gains and losses are detected as deviations from normal diploid cells. We propose that one may consider denoising the data to uncover the true copy number changes before drawing inferences on the patterns of aberrations in the samples. Nonparametric techniques are particularly suitable for data denoising as they do not impose a parametric model in finding structures in the data. In this paper, we employ wavelets to denoise the data as wavelets have sound theoretical properties and a fast computational algorithm, and are particularly well suited for handling the abrupt changes seen in array-CGH data. A simulation study shows that denoising data prior to testing can achieve greater power in detecting the aberrant spot than using the raw data without denoising. Finally, we illustrate the method on two array-CGH data sets.

Breast Neoplasms↗

PubMed2005

Food and botanical groupings and risk of breast cancer: a case-control study in Shanghai, China.

Breast cancer incidence rates more than double in Chinese women as they migrate from China to Hong Kong to the United States, suggesting that environmental factors contribute to the international variation in breast cancer incidence. Several dietary factors, which differ between the United States and the Chinese population, including intake of soy, meat, and fruits and vegetables, have been suggested to affect breast cancer risk. This report describes results from a case-control study of diet and risk of breast cancer nested in a randomized trial of breast self exam in Shanghai, China. Participating breast cancer cases (n = 378) and frequency age-matched controls (n = 1,070) completed a comprehensive food frequency questionnaire and a risk factor questionnaire. After adjustment for age, total energy intake, and total years of breast-feeding, women in the highest quartile of fruit and vegetable intake (> or =3.8 servings/d) were significantly less likely to have breast cancer (odds ratio, 0.48; 95% confidence interval, 0.29-0.78) as compared with women in the lowest quartile of intake (< or =2.3 servings/d). Egg consumption was also significantly inversely associated with risk of breast cancer (odds ratio for > or =6.0 eggs/wk versus < or =2.0 eggs/wk is 0.56; 95% confidence interval, 0.35-0.91). There was no difference in soy consumption between cases and controls. None of the associations with a single botanical family explained the strong inverse relationship between fruits and vegetables and breast cancer risk. These results provide additional evidence in support of the important role of fruits and vegetables in breast cancer prevention.

Adult↗

PubMed2005

[Randomized trial of breast self-examination in 266,064 women in Shanghai].

OBJECTIVE: A randomized trial of breast self-examination (BSE) program was carried out to evaluate whether the intensive BSE can reduce the death number of women from breast cancer. METHODS: A total of 266,064 women (age of 30 to 64 years) associated with 519 textile factories in Shanghai had been randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women) since 1989. Initial instruction in BSE group included demonstration of proper palpation techniques. It was followed by 2 reinforcement sessions during the subsequent 4 years including video shows, BSE instruction sessions and BSE practice under medical supervision. These activities were continued for 5 years. Attendance at all events was recorded. The cohort was followed through July 2000 for development of breast diseases, and the breast cancer cases were followed up through 2001 for vital status. The data analysis methods used included Kaplan-Meier plots, Log-rank test and Cox modeling. RESULTS: Among women under instruction, 864 breast cancers were detected and 133 breast cancer deaths occurred, and 896 breast cancers were detected and 130 deaths recorded in the control group. The tumor size (P = 0.07), TNM stage (P = 0.39) and cumulative breast cancer mortality rate (P = 0.72) were not significantly different between the 2 groups. However, more and smaller fibroadenomas were detected in the instruction group than in the control group (P < 0.01). CONCLUSION: Intensive instruction in BSE can not reduce mortality rate of breast cancer, but more and smaller benign breast lumps can be detected.

Adult↗

PubMed2004

A case-control study of risk factors for fibrocystic breast conditions: Shanghai Nutrition and Breast Disease Study, China, 1995-2000.

This study was conducted to identify reproductive and dietary factors associated with benign proliferative mammary epithelial cell changes. Subjects were women enrolled in a randomized trial of breast self-examination in Shanghai, China. Women who developed fibrocystic breast conditions classified as nonproliferative (175 women), proliferative (181 women), or proliferative with atypia (33 women) between 1995 and 2000 and 1,070 unaffected trial participants were administered general risk factor and food frequency questionnaires. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. High parity and consumption of fresh fruits and vegetables were more strongly associated with a reduced risk of proliferative and atypical lesions than with nonproliferative conditions. For the fourth quartile of consumption versus the first, odds ratios for lesions diagnosed as nonproliferative, proliferative, and proliferative with atypia were 0.4 (95% confidence interval (CI): 0.2, 0.7), 0.2 (95% CI: 0.1, 0.4), and 0.1 (95% CI: 0.03, 0.5), respectively, for fruit intake and 0.6 (95% CI: 0.3, 1.1), 0.4 (95% CI: 0.2, 0.7), and 0.1 (95% CI: 0.1, 0.9), respectively, for vegetable intake. Reduced but nonsignificant risks in relation to soy products were observed for proliferative and atypical lesions. No single nutrient or botanical family was appreciably more strongly associated with proliferative conditions than with nonproliferative conditions, after results were controlled for total fruit and vegetable consumption. A diet rich in fruits and vegetables may reduce cellular proliferation in the mammary epithelium; this is one mechanism by which such a diet could reduce risk of breast cancer.

Adult↗

PubMed2004

UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients.

INTRODUCTION: UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes are involved in removing sex hormones from circulation. Polymorphic variation in five UGT and SULT genes - UGT1A1 ((TA)6/(TA)7), UGT2B4 (Asp458Glu), UGT2B7 (His268Tyr), UGT2B15 (Asp85Tyr), and SULT1A1 (Arg213His)--may be associated with circulating sex hormone concentrations, or the risk of an estrogen receptor-negative (ER-) or progesterone receptor-negative (PR-) tumor. METHODS: Logistic regression analysis was used to estimate the odds ratios of an ER- or PR- tumor associated with polymorphisms in the genes listed above for 163 breast cancer patients from a population-based cohort study of women in western Washington. Adjusted geometric mean estradiol, estrone, and testosterone concentrations were calculated within each UGT and SULT genotype for a subpopulation of postmenopausal breast cancer patients not on hormone therapy 2-3 years after diagnosis (n = 89). RESULTS: The variant allele of UGT1A1 was associated with reduced risk of an ER- tumor (P for trend = 0.03), and variants of UGT2B15 and SULT1A1 were associated with non-statistically significant risk reductions. There was some indication that plasma estradiol and testosterone concentrations varied by UGT2B15 and SULT1A1 genotypes; women with the UGT2B15 Asp/Tyr and Tyr/Tyr genotypes had higher concentrations of estradiol than women with the Asp/Asp genotype (P = 0.004). Compared with women with the SULT1A1 Arg/Arg and Arg/His genotypes, women with the His/His genotype had elevated concentrations of testosterone (P = 0.003). CONCLUSIONS: The risk of ER- breast cancer tumors may vary by UGT or SULT genotype. Further, plasma estradiol and testosterone concentrations in breast cancer patients may differ depending on some UGT and SULT genotypes.

Adult↗

PubMed2004

The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer.

Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27(Kip1), or cyclin D1, but do express p53 and cyclin E. In addition, the expression of cytokeratin 5/6 (CK5/6), indicating a basal epithelial phenotype, is frequent in BRCA1-related breast cancer. Here, in a series of 247 breast cancers, we demonstrate that CK5/6 expression was associated with nearly all of the features of BRCA1-related breast cancer and was also associated with a poor prognosis. In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27(Kip1), p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27(Kip1) levels were independent predictors in lymph node-negative cancers, whereas glomeruloid microvascular proliferation and tumor size independently predicted outcome in node-positive disease. The molecular determinants of the basal epithelial phenotype encapsulate many of the key features of breast cancers occurring in germ-line BRCA1 mutation carriers and have independent prognostic value. Basal breast cancer deserves recognition as an important subtype of breast cancer.

Adult↗

PubMed2004

BRCA1 and BRCA2 mutations in women from Shanghai China.

Little is known about the frequency of germ-line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 among Asian populations. We investigated the distribution of BRCA1 and BRCA2 germ-line mutations and polymorphisms in a cohort of women from Shanghai, China. Study subjects totaled 1306, and included 645 women with breast cancer, 342 women with benign breast disease, and 319 unaffected controls, born between 1924 and 1958, selected from women enrolled in a randomized trial of Breast Self-Examination in Shanghai, China. Women were selected without regard to family history of breast or ovarian cancer. All of the coding regions and exon-intron boundaries were screened. Data were analyzed with respect to age at diagnosis, and family history of breast and ovarian cancer. The prevalence of known disease-associated mutations in women with breast cancer was 1.1% each, for BRCA1 and BRCA2. Among breast cancer cases with a family history of breast or ovarian cancer, 8.1% and 2.7% carried likely BRCA1 and BRCA2 disease-associated mutations, respectively. Overall, these results suggest that inherited susceptibility to breast cancer due to germ-line BRCA1/2 mutations among women with a family history of breast cancer is comparable between women from Shanghai and Caucasian women of Western European descent. Most alterations observed appear unique to the Chinese population, suggesting a resource that will be useful for assessing risk among both Chinese women and United States women of Chinese descent.

Adult↗

PubMed2002

Human leukocyte antigen class II and cervical cancer risk: a population-based study.

The critical role of the human leukocyte antigen (HLA) system in presenting peptides to antigen-specific T cell receptors may explain why only some human papillomavirus (HPV)-infected women progress to cervical cancer. HLA class II DRB1 and DQB1 genes were examined in 315 women with invasive squamous cell cervical cancer (SCC) and 381 control subjects. Increased risks of SCC were associated with DRB1*1001, DRB1*1101, and DQB1*0301, and decreased risks were associated with DRB1*0301 and DRB1*13. Of squamous cell tumors, those containing HPV-16 were different from those not containing HPV-16 for 3 alleles: DRB1*0401, DRB1*07, and DQB1*06. Increased risks of SCC were associated with DRB1*0401-DQB1*0301 (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7) and DRB1*1101-DQB1*0301 (OR, 2.5; 95% CI, 1.4-4.5), and decreased risks were associated with DRB1*0301-DQB1*02 (OR, 0.7; 95% CI, 0.5-1.0) and DRB1*13-DQB1*06 (OR, 0.6; 95% CI, 0.4-0.9) haplotypes. These results add to the evidence that certain HLA class II alleles or allele combinations, or genes linked to them, make some women more susceptible to SCC.

Adolescent↗

PubMed2002

Randomized trial of breast self-examination in Shanghai: final results.

BACKGROUND: Among women who practice breast self-examination (BSE), breast cancers may be detected when they are at an earlier stage and are smaller than in women who do not practice BSE. However, the efficacy of breast self-examination for decreasing breast cancer mortality is unproven. This study was conducted to determine whether an intensive program of BSE instruction will reduce the number of women dying of breast cancer. METHODS: From October 1989 through October 1991, 266,064 women associated with 519 factories in Shanghai were randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women). Initial instruction in BSE was followed by reinforcement sessions 1 and 3 years later, by BSE practice under medical supervision at least every 6 months for 5 years, and by ongoing reminders to practice BSE monthly. The women were followed through December 2000 for mortality from breast cancer. Cumulative risk ratios of dying from breast cancer were estimated using Cox proportional hazards models. All statistical tests were two-sided. RESULTS: There were 135 (0.10%) breast cancer deaths in the instruction group and 131 (0.10%) in the control group. The cumulative breast cancer mortality rates through 10 to 11 years of follow-up were similar (cumulative risk ratio for women in the instruction group relative to that in the control group = 1.04, 95% confidence interval = 0.82 to 1.33; P =.72). However, more benign breast lesions were diagnosed in the instruction group than in the control group. CONCLUSIONS: Intensive instruction in BSE did not reduce mortality from breast cancer. Programs to encourage BSE in the absence of mammography would be unlikely to reduce mortality from breast cancer. Women who choose to practice BSE should be informed that its efficacy is unproven and that it may increase their chances of having a benign breast biopsy.

Adult↗