Analysis of aluminium content and iron homeostasis in nipple aspirate fluids from healthy women and breast cancer‐affected patients

Abstract

Aluminium is not a physiological component of the breast but has been measured recently in human breast tissues and breast cyst fluids at levels above those found in blood serum or milk. Since the presence of aluminium can lead to iron dyshomeostasis, levels of aluminium and iron-binding proteins (ferritin, transferrin) were measured in nipple aspirate fluid (NAF), a fluid present in the breast duct tree and mirroring the breast microenvironment. NAFs were collected noninvasively from healthy women (NoCancer; n = 16) and breast cancer-affected women (Cancer; n = 19), and compared with levels in serum (n = 15) and milk (n = 45) from healthy subjects. The mean level of aluminium, measured by ICP-mass spectrometry, was significantly higher in Cancer NAF (268.4 ± 28.1 μg l(-1) ; n = 19) than in NoCancer NAF (131.3 ± 9.6 μg l(-1) ; n = 16; P < 0.0001). The mean level of ferritin, measured through immunoassay, was also found to be higher in Cancer NAF (280.0 ± 32.3 μg l(-1) ) than in NoCancer NAF (55.5 ± 7.2 μg l(-1) ), and furthermore, a positive correlation was found between levels of aluminium and ferritin in the Cancer NAF (correlation coefficient R = 0.94, P < 0.001). These results may suggest a role for raised levels of aluminium and modulation of proteins that regulate iron homeostasis as biomarkers for identification of women at higher risk of developing breast cancer. The reasons for the high levels of aluminium in NAF remain unknown but possibilities include either exposure to aluminium-based antiperspirant salts in the adjacent underarm area and/or preferential accumulation of aluminium by breast tissues.

Aluminium chloride promotes anchorage‐independent growth in human mammary epithelial cells

“…fda.gov/RegulatoryInformation/Dockets/ucm130350.htm) and in the range of those recently found in the human breast (Exley et al, 2007;Mannello et al, 2009Mannello et al, , 2011. Our findings do not provide conclusive evidence that aluminium is a breast carcinogen.…”

“…Bacterial strains CC105 (upper panel) or ML3 (bottom panel) were grown in the presence or absence of 300 mM AlCl 3 and tested for the indicated mutations through the counting of Lac + revertants or Rifampicin resistants (Rif represents a major route through which the human mammary epithelium is exposed to aluminium. Interestingly, although aluminium concentrations in the body are generally low, levels measured in the breast area (including milk) are relatively high (Mannello et al, 2009(Mannello et al, , 2011Exley et al, 2007). Whether this is due to antiperspirant use or other routes of exposure, and whether it reflects intrinsic metabolic specificities of the breast, is currently not known.…”

“…Overall, little is known about its toxic effects at the cellular and systemic levels, although it is generally acknowledged that aluminium is neurotoxic (Krewski et al, 2007;Kawahara and Kato-Negishi, 2011). With respect to the breast, relatively high levels of aluminium have been measured in the normal human breast adjacent to breast tumours (Exley et al, 2007), in the nipple aspirate fluid collected from women affected by breast cancer (Mannello et al, 2011), and in the fluid collected from breast cysts observed in gross cystic breast disease (Mannello et al, 2009), a benign breast disorder believed to facilitate the appearance of breast cancer. The relatively high levels of aluminium in these settings may result from intrinsic metabolic features of the tissue analysed, thus being purely correlative in nature.…”

Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts

“…Mannello et al (2011) compared Al concentrations in nipple aspirate from 16 healthy women (131 ± 9.6 μg/L) to those in 19 women diagnosed with breast cancer (268 ± 28.1 μg/L). Based on the highly significant (p < 0.0001) difference, Mannello et al (2011) suggested that either human breast tissue accumulates Al or that the elevated Al concentrations were related to use of Al-containing underarm antiperspirants.…”

“…Based on the highly significant (p < 0.0001) difference, Mannello et al (2011) suggested that either human breast tissue accumulates Al or that the elevated Al concentrations were related to use of Al-containing underarm antiperspirants. Following up on that suggestion, Darbre et al (2011) cultured human mammary adenocarcinoma MCF-7 cells with 0 or 0.0001 M (100 μM) ACH (equivalent to 31 μM Al) for 21 weeks.…”