Breast-tissue sampling for risk assessment and prevention

Abstract

Breast tissue and duct fluid provide a rich source of biomarkers to both aid in the assessment of shortterm risk of developing breast cancer and predict and assess responses to prevention interventions. There are three methods currently being utilized to sample breast tissue in asymptomatic women for risk assessment: nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA) and ductal lavage. Prospective single-institution trials have shown that the presence of atypical cells in NAF fluid or RPFNA specimens is associated with an increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been observed to further stratify risk based on the commonly used Gail risk-assessment model. A prospective trial evaluating risk prediction on the basis of atypical cells in ductal-lavage fluid is ongoing. The ability of other established non-genetic biomarkers (mammographic breast density; serum levels of bioavailable estradiol, testosterone, insulin-like growth factor-1 and its insulin like growth factor binding protein-3) to stratify risk based on the Gail model is as yet incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e. hyperplasia with or without atypia) with or without associated breast-tissue molecular markers, such as proliferation, is currently being used to evaluate response in Phase II chemoprevention trials. RPFNA has been the method most frequently used for Phase II studies of 6-12 months duration. However, ductal lavage, RPFNA and random and directed core needle biopsies are all being utilized in ongoing multi-institutional Phase II studies. The strengths and weaknesses of each method are reviewed.

Strategic Approach to Validating Methylated Genes as Biomarkers for Breast Cancer

“…Sources for breast cancer biomarkers include body fluids, such as sera, urine, saliva, ductal lavage (DL), nipple aspirate, and fine needle and core needle biopsy (CNB; Table 1; refs. [11][12][13][14][15][16][17][18][19][20][21][22]. FNA typically involves 8 to 10 aspirations per breast using a 20-to 21-gauge needle.…”

“…The potential promise of DL is to add precision to risk estimation in asymptomatic high-risk women, to allow serial observation of breast epithelial response to preventive agents, and to possibly detect mammographically occult breast cancer. Breast tissue samples have been successfully used for preventive clinical trials (22).…”

In Reply

“…Both NAF biochemical analysis and morphological evaluation of epithelial cells in NAF specimens attempt to improve the identification of high-proliferative epithelium with atypia, recognizing the high metabolic activity through proteomic, degradomic, and genomic approaches [25][26][27], and an accurate cytological grading system [28]. NAF collection may represent a promising noninvasive method for BC risk assessment, especially in asymptomatic women without suspicious lesions on physical exam or mammography [4], and may help to distinguish the most frequent benign lesions of the breast (e.g., inflammatory lesions, fibrocystic changes, stromal lesions, with and/or without atypia and/or hyperplasia) from BC (both in situ and invasive carcinoma), in order to also assess the most appropriate treatment management [29].Finally, the high-quality overview of the clinicopathological features of benign breast lesions by Guray and Sahin [1] should not prescind careful consideration of the possibility of stratifying the risks of BBD in relation to developing subsequent BC through NAF collection and analysis, which provide direct evidence of the early changes in carcinogenesis (at a translational rather than a transcriptional level) [30], useful in identifying women with nonproliferative or proliferative changes at high risk of developing more-advanced precancerous lesions and eventually cancer [24]. The promise of intraductal research is based on the understanding of how the breast works, helping us to determine how to predict and to reverse early cancerous changes.…”

“…In this respect, Guray and Sahin [1] did not report (probably for reasons of brevity) the usefulness of nipple aspirate fluid (NAF) collection, which provides a rich source of biomarkers (Mannello et al, submitted) to both aid in the assessment of the short-term risk for developing BC and predict/assess responses to prevention interventions [24]. Both NAF biochemical analysis and morphological evaluation of epithelial cells in NAF specimens attempt to improve the identification of high-proliferative epithelium with atypia, recognizing the high metabolic activity through proteomic, degradomic, and genomic approaches [25][26][27], and an accurate cytological grading system [28].…”

“…Finally, the high-quality overview of the clinicopathological features of benign breast lesions by Guray and Sahin [1] should not prescind careful consideration of the possibility of stratifying the risks of BBD in relation to developing subsequent BC through NAF collection and analysis, which provide direct evidence of the early changes in carcinogenesis (at a translational rather than a transcriptional level) [30], useful in identifying women with nonproliferative or proliferative changes at high risk of developing more-advanced precancerous lesions and eventually cancer [24]. The promise of intraductal research is based on the understanding of how the breast works, helping us to determine how to predict and to reverse early cancerous changes.…”