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Breast cancer, 300 chemicals identified for investigation

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A new study has identified nearly 300 chemicals that can increase the levels of two hormones in a laboratory test performed on cells: estradiol, progesterone, or both. And about thirty of these could have – the conditional is a must – a carcinogenic effect, in particular against breast cancer. Some are (or were, depending on the country considered) present in pesticides, in common products such as dyes also for hair, combustion products including cigarette smoke, I’m food additives O water contaminants. It should obviously be borne in mind that these are data obtained in vitro – only sometimes in animal models – and not in humans. But the results are interesting precisely because they can contribute to increasing knowledge of the environmental risk factors for this cancer, which needs to be researched.

Breast Health

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What does breast cancer have to do with it? Many risk factors are known that increase the chances of developing this disease: among these there are both the prolonged use of hormone replacement therapies in menopause is the reproductive history (early menarche, late menopause, absence of pregnancy and not having breast-fed), and both factors are thought to act by increasing the activity of estrogen (such as estradiol) and progesterone. For this reason, there is a lot of interest in substances that interfere with hormones, although the direct cause-and-effect link with breast cancer in women has not been proven.

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Research

The study is published on Environmental Health Perspectives, an authoritative journal, and was led by two researchers from the Silent Spring Institute di Newton (USA), a scientific organization dedicated to research on the environmental causes of breast cancer. “One of the concerns is whether endocrine disruptors may increase the risk and progression of breast cancer,” the two authors of the survey write. Bethsaida Cardona e Ruthann A. Rudel, expert in toxicology: “Most breast cancers, in fact, are sensitive to hormones and have receptors for estrogen and progesterone.” However, this does not automatically mean that a substance that increases the levels of these hormones can have an impact on the risk. The point, according to the researchers, is precisely this: it is an aspect that has not yet been investigated as it deserves. Especially considering that breast cancer has become the most diagnosed cancer worldwide this year, outnumbering lung cancer cases. “What we do know is that women are exposed to multiple chemicals every day and these exposures add up. We should be extremely cautious of products that increase hormone levels ”.

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The researchers conducted a complex meta-analysis, starting from data derived from a test developed for the program ToxCast of the Environmental Protection Agency (validated internationally for use in regulatory contexts) on as many as two thousand substances: they have drawn up a list based on their activity in vitro, analyzed 16 studies in vivo (on rodents) and assessments on carcinogenicity and toxicity for development and reproduction. They found 182 substances that increase estradiol levels, 185 that increase progesterone levels, and 71 substances that increase both hormones in cell lines. Also through ToxCast data, they also identified the sources of exposure and predicted the exposure to which women are subject. It must be said that for most substances, however, there is currently insufficient data to evaluate their real effects.

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33 special supervised substances

Among the 300 chemicals identified with this method, 33 are also known to the International Agency for Research on Cancer (IARC): 5 are in fact already classified as “definitely carcinogenic” (Group 1), other 5 as “probably carcinogenic” (Group 2A) and the remaining 23 as “possibly carcinogenic” (Group 2B) for humans, as they write in a comment on the study Kathryn Z. Guyton e Mary K. Schubauer-Berigan of the IARC. “Of all these substances – report the two experts – only the dietilstilbestrolo (a synthetic estrogen used long ago as a drug, ed.) is a recognized risk factor for breast cancer. However, it is interesting to note that some of these carcinogens are linked to other types of cancer in humans, such as bladder, prostate and non-Hodgkin’s lymphoma ”.

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However, many of the active chemicals have not been tested in vivo or evaluated by IARC, and we currently do not have solid carcinogenicity ratings for 56 chemicals that increase estradiol and 63 that increase progesterone: “Several agents – continues Guyton and Schubauer-Berigan – like anthracene (used, for example, to prepare dyes, insecticides and tanning substances, ed.), The bisphenol A (which makes up synthetic resins, ed.), carbaryl, chlorpyrifos, diphenylamine and permethrin (used in pesticides in some countries, ed.) have been recommended for an upcoming evaluation by the IARC, although only a few of them. recommendations are based on solid evidence for breast cancer in humans ”.

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The limits of the study and the difficulties of research on environmental risk factors

“The approach used in this new study is interesting, but it also has many limitations,” he comments Enrico Garattini of the Mario Negri Institute of Pharmacological Research and researcher of the AIRC Foundation in the field of breast oncology and solid tumors: “It is not certain that what is observed in the cell line is generalizable in vivo, and in particular in humans . And it is not automatic that the increase in the level of hormones causes breast cancer. These are therefore predictions and we must be very careful not to draw hasty conclusions. Especially because what we generically call breast cancer is a set of diseases that are also very different from each other. Even within hormone-sensitive breast cancer, which accounts for about 70% of cases, there are huge differences. However, the position of the authors and of the comment of the IARC, according to which research on the environmental factors of breast cancer must be implemented, is absolutely acceptable. The real problem, at least in Italy, is the absolute and structural lack of funds ”.

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Epidemiological studies are an important avenue to clarify any potential link, but so far “sufficient” evidence on environmental risk factors for breast cancer almost all comes from studies conducted on nutrition and drug exposure. “The approach used by Cardona and Rudel – conclude Guyton and Schubauer-Berigan – provides an important example of the application of validated in vitro tests to understand which chemicals should be prioritized for further studies and evaluations”.

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