Another cell culture study joins the list of research investigating the link between environmental chemicals and breast cancer. Although it is too early to make bold claims, this article covers what experts currently believe.

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A new study suggests that some synthetic chemicals could increase the risk of breast cancer by stimulating hormones. Nirut Sangkeaw/EyeEm/Getty Images

We have exposure to dozens of chemicals daily. The air we breathe is made of chemicals — nitrogen, oxygen, and carbon dioxide, among many others — and so is the water we drink. There are also many chemicals that we have created, such as aspirin, which is an effective pain relief drug.

Organizations including the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) rigorously test such chemicals under laws such as the Toxic Substances Control Act before they reach the consumer to ensure that they are safe.

However, could some of these chemicals have yet unexplored health effects?

Ruthann Rudel, research director at the Silent Spring Institute in Newton, MA, and Silent Spring scientist Bethsaida Cardona started their research with that question in mind.

They sought to identify preventable causes of breast cancer and investigated which chemicals might contribute to an increased risk of this condition.

As part of their study, Rudel and Cardona went through data on 2,000 chemicals listed in the EPA’s Toxicity Forecaster, which is a program that screens chemicals for potential health hazards.

Their paper appears in the journal Environmental Health Perspectives.

In their review, the researchers found 296 chemicals that caused an increase in levels of estradiol, which is a form of estrogen and the major female sex hormone, progesterone levels, or both estradiol and progesterone in adrenal cell culture.

Of these chemicals, 71 caused an increase in both hormones. They included chemical flame retardants, dyes, fungicides, and pesticides.

Some of the chemicals implicated included:

  • 1,2-Diphenylhydrazine: This is a chemical that manufacturers use in the production of dyes, pharmaceuticals, and hydrogen peroxide.
  • Malathion: This is an insecticide in the chemical family known as organophosphates. People commonly use it in mosquito control.
  • Phosmet: This is an organophosphate insecticide that people use for protecting apple trees.
  • Oxyfluorfen: This is an herbicide with widespread use in agriculture, specifically for weed control.

“In this study,” Rudel told Medical News Today, “we used new data produced by EPA to identify commonly used chemicals that have been shown to increase the synthesis of estrogen and progesterone in cells in a dish because this is directly relevant to hormone receptor [HR]-positive breast cancer.”

“There’s been a fair bit of attention on identifying chemicals that bind to and activate the estrogen receptor — essentially mimicking estrogen — but no one had identified chemicals that increase the synthesis of estrogen or progesterone, so we used the new data to do that.”

The findings suggest that some of these synthetic chemicals could increase the risk of breast cancer by way of stimulating the two hormones linked to breast cancer: estrogen and progesterone.

Previous studies into endocrine-disrupting chemicals had focused only on the chemicals’ ability to bind directly to the estrogen receptor and activate it. In that sense, this study introduces a new dimension to breast cancer research.

“Since many environmental chemicals would not be as strong activators as endogenous estradiol, the weaker activity limited concerns in some assessments,” said Rudel. “However, since the chemicals we identified increase the synthesis of estradiol, which is very potent, the effects of these chemicals on breast cancer may be much stronger [than thought].”

Past studies have suggested that inhibiting or reducing estradiol was effective in preventing or treating breast cancer.

Similarly, in one randomized trial, using a mixture of estrogen plus progestin — which is the synthetic form of progesterone that the body produces naturally — in hormone replacement therapy was shown to increase breast cancer risk.

However, scientists are still trying to establish how these chemicals are achieving this increase in estradiol.

One way, they hypothesize, is that these chemicals could be acting as aromatase activators — the opposite of drugs such as tamoxifen — and causing cells to produce more of these hormones.

The study also points out that regular exposure from multiple sources rather than one-off or rare exposures is likely to have an effect.

How do estrogen and progesterone cause cancer?

Two out of three cases of breast cancer are HR-positive, according to the American Cancer Society. Being HR-positive means that the cancer cells may receive chemical signals from sex hormones that could promote their growth.

Most HR-positive breast cancer cases are estrogen receptor-positive.

Estrogen can cause cancer in two ways. It can stimulate breast tissue to encourage cells to divide and duplicate, during which some mutations may occur. Estrogen metabolites can also have carcinogenic potential by causing DNA damage and contributing to the development of breast cancer.

Similarly, progesterone receptor-positive breast cancer is sensitive to the hormone progesterone. Cells, in these cases, have receptors that allow them to use this hormone to grow.

Hormone therapy can prevent tumors from using estrogen or progesterone, thereby slowing or stopping tumor growth, or they can lower levels of these hormones in the body.

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The study adds to research exploring additional risk factors for breast cancer that scientists have yet to identify.

“The role of environmental pollutants in breast carcinogenesis is particularly poorly understood, yet there are understandable public concerns about the role of broad, low-level exposure to environmental pollutants,” said Dr. Lauren Teras, Ph.D., the scientific director of epidemiology research at the American Cancer Society.

However, studying possible links between cancer and chemicals proves troublesome.

The short half-life of some chemicals, the length of time over which cancer develops, the cumulative exposure to chemicals and various mixtures, and having different physiologic characteristics could determine whether or not these chemicals will impact the body and, if so, to what extent, said Dr. Teras.

Although it is interesting to see these chemicals having an effect, people should interpret the data with caution. Dr. Janie Grumley, surgical breast oncologist and director of the Comprehensive Breast Program at the Margie Petersen Breast Center in Santa Monica, CA, agrees.

“This [research] was in a very controlled in vitro situation, which is the biggest area of caution because it does not necessarily apply to human beings. And when reading something like that, we definitely do not want to jump to conclusions,” Dr. Grumley told MNT.

She likened it to mapping out a route for a trip. “You mark point A and B, and you draw a straight line, and you think O.K., we are going to get there. But in reality, when you actually take that trip, there are lots of things that are unexpected. There are mountains and hills and oceans and things that you can’t really anticipate and may not be turn out to be anything,” she said.

According to Dr. Teras, the results of the study are not surprising.

“We are continuing to learn about the complex ways in which our environment plays a role in human health. However, no one study stands alone. Though this study presents a nice summary of chemicals that deserve further investigation, I do not view this as a list of chemicals that is ready for clinical action,” she told MNT.

The next step would be to determine whether or not these chemicals produce the same effect in animals and humans.

Rudel said that their review also explored the types of effects reported when scientists tested these chemicals in experimental animals. The chemicals, she said, were likely identified as carcinogens or reproductive/development toxicants if tested. However, many had not undergone testing in that regard.

Chemicals reported to affect mammary glands in experimental animals have also been found to influence breast cancer risk by increasing the synthesis of estradiol, progesterone, or both.

According to Rudel, current methods for chemical safety testing appear to be missing breast-related effects, including effects on breast development, puberty, lactation, and cancer.

“Doing this study really opened my eyes to the fact that our chemical testing approaches are missing potential breast cancer risks because we simply aren’t looking for them,” she said.

“It’s common knowledge in the breast cancer community that estrogen and progesterone are risk factors, and first-line treatments for [HR]-positive breast cancer are to reduce levels of these or block the estrogen receptor so estrogen can’t make the cells divide,” she told MNT.

The researchers recommend strengthening methods to check for likely breast effects when testing chemicals and identifying possible carcinogens before they end up in consumer products.

They also suggest limiting people’s exposures to such chemicals during critical stages of development, such as puberty and pregnancy.

If companies are using the chemicals that have effects on estrogen or progesterone synthesis, “they should invest and could try to tease it out further, knowing that there may be something,” said Dr. Grumley.

“If nothing alarming comes out of it, they can continue to use the product, but if there is, they can take responsibility and produce alternatives or make efforts in that regard,” she added.

The study has raised an interesting point in research to identify breast cancer risk by focusing on chemicals that increase estrogen or progesterone. However, without in vivo studies, it is premature to try to establish a definitive link.

A multi-pronged approach is necessary to get a full understanding of the role that chemicals play in developing breast cancer. This should encompass all data from cell, animal, and observational human studies, according to Dr. Teras.

“The human body is [also] extremely complex, and studying one piece of the puzzle in isolation may be very different from what happens when all the pieces come together.”

– Dr. Lauren Teras, Ph.D.

“Even though the findings are interesting, we cannot take that and apply it to human beings until we do further assessments,” added Dr. Grumley.

Evaluating the effects of these chemicals on humans remains challenging, and most have not undergone adequate study.

In that sense, the new study can direct future research into examining the effects that chemicals may have on mammary glands, such as tumors.

“So, we expect that more rigor should be applied in interpreting observations of chemically induced changes in mammary tissue,” said Rudel.