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Darbre. J Cancer Metastasis Treat 2019;5:58 I http://dx.doi.org/10.20517/2394-4722.2019.22 Page 9 of 13

Figure 2. Diagrammatic representation of how estrogen disrupting chemicals may influence metastasis of breast cancer cells. Through
their estrogenic activity, they may increase growth of cells at the primary site in the breast or at metastatic sites. They may enable
EMT, increase cell migration and cell invasion. Through their widespread presence in the human body, they may provide a favourable
microenvironment for colonization and metastatic tumour growth

CONCLUSIONS
It can be concluded that there is mounting evidence for a role of estrogen disrupting chemicals in
contributing to the processes of metastatic tumour spread and this is summarized in Figure 2. Estrogen
disrupting chemicals may contribute to loss of cell-cell adhesion, development of EMT and increased
secretion of ECM-degrading proteases leading to increased cell motility, migration and invasion. However,
estrogen disrupting chemicals are also likely to play a role in creating a favourable microenvironment for
colonization and growth of metastatic tumours at distant sites. Unpredictable awakening from dormancy [7]
could result from altered environmental exposures or indeed sudden release of estrogen disrupting
chemicals from fat stores such as at times of weight loss. It is well established that estrogen disrupting
[78]
chemicals are passed from mother to child in breast milk as they are mobilized with the fat in the milk .
Such detoxification of the the mother’s breast may provide an alternative explanation for the protective
[79]
effect of breast feeding on incidence of breast cancer . Likewise, release of estrogen disrupting chemicals
[7]
from storage could change the microenvironment for “dormant niches” causing renewed proliferation.
Research is now needed to answer outstanding questions concerning the effects of long-term exposure
[80]
to low doses of chemicals and the effects of complex mixtures of chemicals . Since estrogen disrupting
chemicals are widely measurable in human tissues and some can bioaccumulate with age, then it follows
that breast cells are exposed long term which requires long term cell culture modelling for further
understanding. This is especially poignant in the acquisition of increased migratory and invasive
properties described above which generally took weeks rather than days to develop. The effects of mixtures
of chemicals each at low dose will be more difficult to resolve because personal lifestyle choices will
inevitably result in differing chemical contents between individuals. Furthermore, due to the additive and
[81]
complementary mechanisms of estrogen disrupting chemicals , different mixtures may have the same
outcomes which makes tracing individual culprit chemicals impossible. However, if specific environmental
exposures can be uncovered, then avoidance would be a good strategy for prevention. In 2001, I proposed
a hypothesis that regular application of constituents of underarm cosmetics might play a role in the rising