The physiology of the normal human breast: an exploratory study

Abstract

The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

The changing microRNA landscape by color and cloudiness: a cautionary tale for nipple aspirate fluid biomarker analysis

“…Identifying the underlying cause of these different NAF colors in healthy women may explain our findings. We hypothesize that several potential factors may contribute to NAF color such as diverse cellular [54] or bacterial [55] compositions in NAF samples, nutrients and proteins [56][57][58], medications [59][60][61][62] or food intake [62][63][64][65][66][67][68]. But studies addressing the association between these possible factors and color classes are limited.…”

New Exposure Biomarkers as Tools for Breast Cancer Epidemiology, Biomonitoring, and Prevention: A Systematic Approach Based on Animal Evidence

“…Breast milk is a valuable medium for exposure monitoring because it can be collected noninvasively at substantial volume, the high fat content captures lipophilic compounds, and it reflects exposures to young women and infants. Other matrices that can be used for biomonitoring include fine-needle aspirates of breast ductal fluid (Mills et al 2011), hair (e.g., Bessette et al 2009), adipose tissue (e.g., Covaci et al 2002; Dewailly et al 1999; Falk et al 2012), saliva (e.g., Bessette et al 2010), exhaled breath (e.g., Cope et al 2004; Plebani et al 1999), and fingernails (Esteban and Castaño 2009). …”

Modeling and analysis of transport in the mammary glands

“…Extensive experimental procedures performed in human mammary glands can be challenging and sometimes almost impossible [25]. Even with these limitations, we are able to provide an alternative to understanding how the toxins get into the breast milk.…”

“…Our approach is that it will provide an alternative to estimate the milk to plasma ratio (M/P ratio) for breastfeeding women. Research publications have shown that toxins are able to penetrate the epithelial layers and get into the breast milk in higher concentrations compared to the resting mammary gland [6,8,9,11,12,[25][26][27][28][29][30]. This work takes into consideration the particle size and properties of the layers to estimate the percentage of toxins that are introduced into the breast milk.…”