Peggy L. Porter
M.D., University of New Mexico, Albuquerque, 1987.
Work in my lab is focused on identifying and understanding the molecular events associated with the initiation and progression of human cancer, particularly the role of abnormal cell proliferation. The clinical significance of these events in malignant and pre-malignant lesions of breast and ano-genital human tumors is of primary interest and our involvement in collaborative research provides a unique opportunity for translational of basic science discoveries to questions that can be posed in large, clinical and population-based studies.
The current model of carcinogenesis is that of a multi-step accumulation of genetic changes within cells that supplant normal controls on cell division and lead to increased cell proliferation. Abnormalities of the cell cycle in a highly proliferative cell population may then lead to additional molecular alterations. In fact, recent advances in our understanding of cell cycle mechanisms indicate that derangements in the cell cycle may not only contributeto uncontrolled cell growth but may be causal factors in the development of cancer. In collaboration with Drs. James Roberts, Janet Daling and Kathi Malone, we have identified associations between high levels of cyclin E, and low levels of the cell cycle inhibitor p27, with poor clinical outcome in a group of young women with breast cancer. The associations were most pronounced in women with lymph node negative disease, a finding that could greatly impact clinical management in this group of women.
We continue to investigate the role of aberrant expression of cell cycle proteins in pre-invasive breast and ano-genital tumors order to evaluate the role of cell cycle changes in the progression from in situ to invasive disease. We find significantly lower levelsof expression of cyclin E in in situ breast neoplasia than in invasive tumors, indicating a possible role in the transition to a malignant phenotype. We are currently examining patterns of expression of a set of cell cycle proteins which are representative of independent regulatory pathways (Cyclin D/Rb/p16 and Cyclin E/ p27), for the purpose of establishing a collection of markers in breast and ano-genital cancers, which together provide the most information about the status of cell cycle controls in individual tumors. Assessment of cell cycle regulators and their expression during the cell cycle will be facilitated by our development of multivariate flow cytometric assays in fixed tumor specimens.
Although we and others have successfully identified molecular markers of tumorigenesis using conventional approaches, single gene and protein changes are also unlikely to reflect the complexity of the molecular changes present in tumor cell populations. Using global approaches, made possible by developments in microarray technology and the identification of genes in the human genome project, we are now in a position to elucidate the molecular components, and the connections between the components, that coincide with the acquisition of malignant traits. We are conducting discovery projects using array CGH, SNP array, and expression array in studies of precursor and malignant lesions that will help to better understand, and respond appropriately to, the clinical heterogeneity of breast cancer.
An international study to increase concordance in Ki67 scoring.. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.. 2015.
Oral contraceptives and breast cancer risk overall and by molecular subtype among young women.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.. 2014.
Mislocalization of p27 to the cytoplasm of breast cancer cells confers resistance to anti-HER2 targeted therapy.. Oncotarget. 5(24):12704-14.. 2014.
Use of menopausal hormone therapy and risk of ductal and lobular breast cancer among women 55-74 years of age.. Breast cancer research and treatment.. 2014.
Long-Term Statin Use and Risk of Ductal and Lobular Breast Cancer among Women 55 to 74 Years of Age.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 22(9):1529-37.. 2013.
Reproductive factors and risk of estrogen receptor positive, triple-negative, and HER2-neu overexpressing breast cancer among women 20-44 years of age.. Breast cancer research and treatment. 137(2):579-87.. 2013.
Use of Antihypertensive Medications and Breast Cancer Risk Among Women Aged 55 to 74 Years.. JAMA internal medicine.. 2013.
Breast Density, Body Mass Index, and Risk of Tumor Marker-Defined Subtypes of Breast Cancer.. Annals of epidemiology. 22(5):340-348.. 2012.
Assessment of palindromes as platforms for DNA amplification in breast cancer.. Genome research. 22(2):232-45.. 2012.
Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women.. Breast cancer research and treatment. 127(1):297-308.. 2011.
Reproductive history and risk of three breast cancer subtypes defined by three biomarkers.. Cancer causes & control : CCC. 22(3):399-405.. 2011.
Gene expression array testing of FFPE archival breast tumor samples: an optimized protocol for WG-DASL sample preparation.. Breast cancer research and treatment. 125(3):879-83.. 2011.
Family History of Breast Cancer in Relation to Tumor Characteristics and Mortality in a Population-Based Study of Young Women with Invasive Breast Cancer.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 20(12):2560-2571.. 2011.
Age-related variation in the relationship between menopausal hormone therapy and the risk of dying from breast cancer.. Breast cancer research and treatment. 126(3):749-61.. 2011.
Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk.. Breast cancer research and treatment. 126(3):671-8.. 2011.
Problem solving for breast health care delivery in low and middle resource countries (LMCs): consensus statement from the Breast Health Global Initiative.. Breast (Edinburgh, Scotland). 20 Suppl 2:S20-9.. 2011.
Fruit and vegetable intakes are associated with lower risk of breast fibroadenomas in Chinese women.. The Journal of nutrition. 140(7):1294-301.. 2010.
Multiplexed assessment of the Southwest Oncology Group-directed Intergroup Breast Cancer Trial S9313 by AQUA shows that both high and low levels of HER2 are associated with poor outcome.. The American journal of pathology. 176(4):1639-47.. 2010.
Adjuvant hormonal therapy for breast cancer and risk of hormone receptor-specific subtypes of contralateral breast cancer.. Cancer research. 69(17):6865-70.. 2009.
The epidemiology of triple-negative breast cancer, including race.. Cancer causes & control : CCC. 20(7):1071-82.. 2009.
Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor-positive invasive breast cancer.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 27(32):5312-8.. 2009.
Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA.. Breast cancer research and treatment. 113(2):357-70.. 2009.
Outcome of patients with early-stage breast cancer treated with doxorubicin-based adjuvant chemotherapy as a function of HER2 and TOP2A status.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 27(24):3881-6.. 2009.