Mammographic density does not correlate with Ki-67 expression or cytomorphology in benign breast cells obtained by random periareolar fine needle aspiration from women at high risk for breast cancer

BackgroundKi-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. Mammographic breast density is a risk biomarker and is also being used as a response biomarker. We previously showed that Ki-67 expression is higher in specimens of benign breast cells exhibiting cytologic atypia that are obtained by random periareolar fine needle aspiration (RPFNA). It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA.MethodsIncluded in the study were 344 women at high risk for developing breast cancer (based on personal or family history), seen at The University of Kansas Medical Center high-risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment plus a mammogram. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by χ2 test, and continuous variables were analyzed by nonparametric test and linear regression.ResultsForty-seven per cent of women were premenopausal and 53% were postmenopausal. The median age was 48 years, median 5-year Gail Risk was 2.2%, and median Ki-67 was 1.9%. The median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality (atypia versus no atypia; P ≤ 0.001) and younger age (≤50 years versus >50 years; P ≤ 0.001). Mammographic density was higher in premenopausal women (P ≤ 0.001), those with lower body mass index (P < 0.001), and those with lower 5-year Gail risk (P = 0.001). Mammographic density exhibited no correlation with Ki-67 expression or cytomorphology.ConclusionGiven the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers in breast cancer chemoprevention trials.

[1]  N. Boyd,et al.  Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian Diet and Breast Cancer Prevention Study Group. , 1997, Journal of the National Cancer Institute.

[2]  N. Boyd,et al.  The association of histological and radiological indicators of breast cancer risk. , 1988, British Journal of Cancer.

[3]  Linda Olson,et al.  Effects of Estrogen and EstrogenProgestin on Mammographic Parenchymal Density , 1999, Annals of Internal Medicine.

[4]  J. Wolfe,et al.  Correlative studies of the histological and radiographic appearance of the breast parenchyma. , 1978, Radiology.

[5]  A. Miller,et al.  Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. , 1995, Journal of the National Cancer Institute.

[6]  C. Zalles,et al.  Comparison of cytomorphology in specimens obtained by random periareolar fine needle aspiration and ductal lavage from women at high risk for development of breast cancer , 2006, Breast Cancer Research and Treatment.

[7]  I. Ellis,et al.  The relationship of "high risk" mammographic patterns to histological risk factors for development of cancer in the human breast. , 1990, The British journal of radiology.

[8]  M. Mayo,et al.  Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail risk model. , 2000, Journal of the National Cancer Institute.

[9]  Cellular proliferative activity of mammographic normal dense and fatty tissue determined by DNA S phase percentage , 2005, Breast Cancer Research and Treatment.

[10]  David Tritchler,et al.  Heritability of mammographic density, a risk factor for breast cancer. , 2002, The New England journal of medicine.

[11]  A. Giuliano,et al.  Dietary fat reduction in postmenopausal women with primary breast cancer: Phase III Women's Intervention Nutrition Study (WINS) , 2005 .

[12]  N F Boyd,et al.  The association of breast mitogens with mammographic densities , 2002, British Journal of Cancer.

[13]  R. Warren,et al.  Can the stroma provide the clue to the cellular basis for mammographic density? , 2003, Breast Cancer Research.

[14]  A. Morrison,et al.  Relationship between mammographic and histologic features of breast tissue in women with benign biopsies. , 1988, Cancer.

[15]  Navin Parekh,et al.  Effects of mammographic density and benign breast disease on breast cancer risk (United States) , 2001, Cancer Causes & Control.

[16]  J. Sloane,et al.  Breast cancer risk in usual ductal hyperplasia is defined by estrogen receptor-alpha and Ki-67 expression. , 2002, The American journal of pathology.

[17]  L. Gray,et al.  A Clinicopathologic Correlation of Mammographic Parenchymal Patterns and Associated Risk Factors for Human Mammary Carcinoma , 1982, Annals of surgery.

[18]  S. Masood,et al.  Prospective evaluation of radiologically directed fine‐needle aspiration biopsy of nonpalpable breast lesions , 1990, Cancer.

[19]  W. Willett,et al.  Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density. , 2000, Cancer research.

[20]  C. Zalles,et al.  Ki-67 Expression in Benign Breast Ductal Cells Obtained by Random Periareolar Fine Needle Aspiration , 2005, Cancer Epidemiology Biomarkers & Prevention.

[21]  Stephen W Duffy,et al.  Tamoxifen and breast density in women at increased risk of breast cancer. , 2004, Journal of the National Cancer Institute.

[22]  A. Miller,et al.  Mammographic densities and the prevalence and incidence of histological types of benign breast disease , 2000, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[23]  M. Dowsett,et al.  Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  D. Grobbee,et al.  Heritable Aspects of Dysplastic Breast Glandular Tissue (DY) , 2004, Breast Cancer Research and Treatment.

[25]  R. Chlebowski.  Obesity and early-stage breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  M Moskowitz,et al.  Mammographic patterns as markers for high-risk benign breast disease and incident cancers. , 1980, Radiology.

[27]  E. Perez,et al.  Advances in screening, diagnosis, and treatment of breast cancer. , 2004, Mayo Clinic proceedings.

[28]  L W Bassett,et al.  Effects of estrogen and estrogen-progestin on mammographic parenchymal density. Postmenopausal Estrogen/Progestin Interventions (PEPI) Investigators. , 1999, Annals of internal medicine.

[29]  S. Kamel,et al.  Cytology Patterns in Random Aspirates from Women at High and Low Risk for Breast Cancer , 1995 .

[30]  N. Boyd,et al.  Relationship between mammographic and histological risk factors for breast cancer. , 1992, Journal of the National Cancer Institute.

[31]  E. Fisher,et al.  The histopathology of mammographic patterns. , 1978, American journal of clinical pathology.

[32]  M. Pike,et al.  Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity , 2006, Breast Cancer Research.