Link Between Parabens and Breast Cancer?

Roxanne Nelson

January 26, 2012

January 26, 2012 — Can the use of antiperspirants and deodorants increase the risk for breast cancer?

Data from a study published online January 12 in the Journal of Applied Toxicology could relieve some of the fears about using underarm products, but could also raise questions and concerns.

The issue centers on exposure to alkyl esters of p-hydroxybenzoic acid (parabens), which are widely used as antimicrobial preservatives in pharmaceuticals, foods, and cosmetics. About 10 years ago, note the researchers, studies began to reveal that parabens had estrogenic properties, and estrogen plays a central role in the development, growth, and progression of breast cancer.

In this new study, researchers in the United Kingdom examined 160 breast-tissue samples obtained from 40 patients who had undergone a mastectomy for primary breast cancer. They found that 99% of samples had traces of at least 1 paraben, and that 60% had traces of 5 different parabens.

Importantly, 7 of the women reported never having used underarm products. This suggests that the parabens originated from another source, note the authors.

The source of the parabens measured in this and in previous studies cannot be identified; it is also not clear if the paraben traces come from long-term accumulation, current exposure, or a combination of both.

Parabens are only one part of a much bigger picture.

"I do think that the parabens are only one part of a much bigger picture," said lead author Philippa D. Darbre, PhD, a reader in oncology at the University of Reading, United Kingdom.

"That is not to say that they do not contribute, but the issue is bigger," she told Medscape Medical News. "Parabens are only one component...of personal care products. What is needed now is...a map of what chemicals there are in a human breast in the modern world and how they distribute across the breast, especially in relation to the site of the tumor."

Adding to the Evidence

In their study, Dr. Darbre and colleagues found a disproportionate incidence of breast cancer in the upper outer quadrant of the breast. In all 40 women, levels of n-propylparaben were higher in the axilla region than in the mid or medial regions (Wilcoxon matched pairs test, P = .004 and P = .021, respectively).

This finding is not unusual; a number of studies over the past several decades have reported that a disproportionately high number of breast tumors in women originate in the upper outer quadrant of the breast, "for which a definitive explanation remains lacking," the authors write. This disproportionality has been increasing in the United Kingdom, and now exceeds 50% of breast cancers.

"The detection of intact esters is more suggestive of a dermal route of exposure," said Philip W. Harvey PhD, a registered toxicologist at Covance Laboratories Ltd, North Yorkshire, United Kingdom, who was not involved in the study. "Oral exposure results in the rapid conversion of the esters to the common metabolite p-hydroxybenzoic acid in both gut and liver. The skin has a much lower esterase capacity, which may explain the fact that 5 different intact paraben esters were found."

Dr. Harvey told Medscape Medical News that the gradient or differential concentrations between zones with the highest levels in the axilla are consistent with a dermal route of exposure. "If the residues derive from dermal sources, the highest concentrations are likely to be at the site of exposure," said Dr. Harvey, who is editor-in-chief of the Journal of Toxicology. "That the axilla shows the highest concentrations is consistent with local application and implicates any products applied there."

He emphasized that Dr. Darbre and colleagues did not investigate causal mechanisms of breast cancer, and did not claim that either parabens or underarm products actually caused the cancer in the patients studied. "However, it does add to the dataset that these weakly estrogenic chemicals are found in significant quantities in estrogen-sensitive tissue," he noted. "Not all women will be sensitive to this, but...there will be a proportion of women who are sensitive."

Causal Relationship Undetermined

Personal care products have been used since the days of Cleopatra, but unprecedented quantities are being used nowadays, and are ultimately being released into the environment, explained Dr. Darbre. Investigations have shown that there is widespread aquatic environmental pollution stemming from use, and therefore little doubt that these chemicals are entering human tissues. The human breast has "become a sink for lipophilic compounds due to its high adipose tissue content," she said.

However, in a previous paper, Dr. Darbre and colleagues pointed out that it remains to be determined whether there is any causal relation between individual or combinations of chemicals and the development of breast cancer (CML Breast Cancer. 2010;22:113-122). The real environmental impact of estrogenic chemicals needs to comprise the entire chemical load in the breast.

An increasing number of environmental chemicals with estrogenic properties have been measured in human breast tissues, the authors of that paper write, which shows that the human breast is exposed to many estrogenic compounds in low doses and over a long period of time. These chemicals could act synergistically to "produce an estrogenic stimulus even at concentrations at which each alone would be ineffective."

There is a gap in our understanding of the combined effect of different chemicals in a single human breast, the authors note, because reports of measurements to date have generally evaluated only single groups of chemicals in any one study group.

"In the meantime, I remain rather ambivalent about hounding just one chemical," said Dr. Darbre. "My advice remains as always — to cut down on, or cut out as much as possible, overall use of personal care products, especially those left on the skin around the breast area."

"When even the water systems are now having to remove personal care product compounds from them, we must be simply using too much in the modern world — too much for our own bodies and too much even for the environment," she added. "The only way forward at the moment is for us all to cut down."

Higher Levels Seen

In this study, Dr. Darbre and her team measured the concentrations of 5 parabens at 4 serial locations in the human breast, from the axilla to the sternum, using tissue samples collected in from 2005 to 2008.

The authors found that at least 1 paraben ester was quantifiable in 158 of 160 specimens (99%), and that all 5 esters were quantifiable in 96 of 160 specimens (60%).

The overall median value for total parabens in the breast tissue was 85.5 ng/g (range, 0.0 to 5134.5 ng/g). This level is 4 times higher than the 20.6 ng/g seen in a smaller previous study, which was also led Dr. Darbre (J Appl Toxicol. 2004;24:5-13).

The highest values were observed for n-propylparaben, at 16.8 ng/g (range, 0.0 to 2052.7), and methylparaben, at 16.6 ng/g (range, 0.0 to 5102.9). They were much lower for n-butylparaben, at 5.8 ng/g (range, 0.0 to 95.4), ethylparaben, at 3.4 ng/g (range, 0.0 to 499.7), and isobutylparaben, at 2.1 ng/g (range, 0.0 to 802.9).

More Research Needed

Dr. Harvey noted that the dataset is sparse and there is a need for further research. "The rising incidence of breast cancer in recent decades points to environmental or lifestyle factors, and chemical exposure — of which the cosmetics scenario is one of the most obvious for direct dermal exposure — is just one implicated factor, together with all the other known factors for breast cancer," he said.

In addition, the regulatory toxicology dataset on parabens as a whole needs to be updated, he added, noting that European regulators are slowly taking steps on information that is coming to light, specifically reducing permitted concentrations of some paraben esters.

"The wisdom of putting estrogenic chemicals in any dermal product must be questioned, particularly compounds with an old regulatory toxicology dataset that probably does not achieve adequate modern standards, and particularly where current-use patterns already indicate that there is insufficient margins of safety in some groups, such as children," Dr. Harvey said.

It is easy to say that there is no evidence of parabens or cosmetics being associated with a health effect if the research has not been done.

"The whole area is poorly researched, but it's now time to coordinate funding and support into a few key areas of environmental endocrine disruption and human health, and the cosmetics scenario is one of the most promising to study in a controlled way," he emphasized. "It is easy to say that there is no evidence of parabens or cosmetics being associated with a health effect if the research has not been done; indeed, the statement is misleading to the public."

Michael J. Thun, MD, vice president emeritus of epidemiology and surveillance research at the American Cancer Society, cautioned that this analysis not be misinterpreted. "The purpose was not to study whether parabens in general or underarm deodorants affect breast cancer risk," he said. "Rather, it examined the levels and anatomic distribution of various paraben compounds in the excised breasts of 40 women with breast cancer."

However, he agrees that more research is needed. "Questions have been raised about their safety because parabens are absorbed through the skin and trace amounts can be detected in tissues, including breast tissue," he explained. "Parabens weakly mimic the effects of estrogen, a hormone known to play a role in breast cancer. No study has yet shown that the concentration of parabens in breast tissue taken from women with breast cancer are higher than that in breast tissue of women without breast cancer. A well-designed study of this issue would be useful."

The Genesis Breast Cancer Prevention Appeal funded the salary of a clinical research fellow and the cost of the liquid chromatography–tandem mass spectrometry analysis. The authors have disclosed no relevant financial relationships.

J Appl Toxicol. Published online January 12, 2012. Abstract

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