50-Year Data Link Pesticide to Breast Cancer

First Study to Find Link

Veronica Hackethal, MD

June 16, 2015

There is a significant association between in utero exposure to the pesticide DDT, which was widely used in the 1960s in the United States before being banned, and the risk for breast cancer in young women, according to new research from the state of California.

The study investigators also say there is a "possible association" with more aggressive tumors and exposure to DDT, which is a synthetic estrogen and a possible endocrine disruptor.

"Our findings support the idea that the breast may be particularly vulnerable in utero," commented lead author Barbara Cohn, PhD, of the Public Health Institute, in Berkeley, California.

The nested case-control study is, remarkably, the first to directly link in utero exposure to an environmental chemical to breast cancer.

The "unique" study was made possible by 54-year follow-up of the Child Health and Development Studies (CHDS) cohort in California, which enrolled pregnancies from 1959 to 1967, a period that is coincidentally the "years of highest DDT exposure" in the United States.

A total of 9300 female babies were born into the cohort study, which had the goal of examining "prenatal exposures and health and development over the life course for parents and children."

There were 118 breast cancer cases diagnosed by age 52 years, and investigators identified 345 control individuals who were matched by birth year. The cancers were found using state registry records and a self-report survey of CHDS daughters from 2010 to 2013.

The researchers then went back and determined levels of in utero exposure to DDT in the case patients and control participants by analyzing frozen, stored blood samples from their respective mothers given during pregnancy and 1 to 3 days after delivery in the 1960s.

What they found was groundbreaking.

"The size of the DDT association with breast cancer in our study — a fourfold increase in risk for women in the top 25% of DDT exposure compared to the bottom 25% — is larger than for many known behavioral risk factors for breast cancer," said Dr Cohn.

She explained that daughters born to mothers with increased serum levels of o,p'-DDT ― which is a more estrogenic form of DDT found in commercial pesticides ― had a nearly fourfold increased risk for breast cancer (odds ratio [OR] fourth quartile vs first = 3.7; 95% confidence interval [CI], 1.5 - 9.0; P = .004). This was found regardless of the mother's history of breast cancer.

Notably, 83% of the women had estrogen-receptor-positive breast cancer.

Further analyses linked DDT to advanced stage at diagnosis (estimated OR, 2.2; 95% CI, 1.1 - 4.2; P = .2) and to HER2-positive tumors (estimated OR, 2.1; 95 CI, 1.0 - 4.8; P = .05).

Daughters of women with triple the amount of exposure to DDT had four times the risk of developing advanced-stage and HER2-positive breast cancer compared with daughters of women with lower levels of exposure (for late-stage: OR, 4.6; 95% CI, 1.3 - 16.5; for HER2-positive: OR, 4.6; 95% CI, 1.1 - 19.7).

Laboratory studies have provided support for these findings and suggest that DDT activates the HER2 receptor, write the authors in their article, published online June 16 in the Journal of Clinical Endocrinology and Metabolism.

"Although our human study is not proof of causation, it may be prudent to protect women of childbearing age from avoidable DDT exposure in countries where it is still used," advised Dr Cohn.

The United States and Europe banned DDT in the 1970s, but Asia and Africa continue to use it for malaria control.

"Since some environmental chemicals may be stored in the body for long periods, it may also be prudent to protect children from unnecessary chemical exposures," she added. "Avoiding unnecessary additional exposures to other suspect environmental chemicals is a possible step for women already previously exposed to DDT."

Although the increased risk may be concerning for women exposed to DDT in utero, Dr Cohn put it into perspective.

"The baseline risk of breast cancer for a woman at age 50 is still low ― 2.38%. Increasing that risk fourfold is still a low risk," she reassured.

"All women, whether or not they suspect in utero DDT exposure, should discuss an early detection and prevention strategy with their doctor, who will know their personal history and personal risk," she emphasized.

The present study investigates breast cancer diagnosed before age 52 years. Thus, these results do not address DDT associations with breast cancer diagnosed at an older age, write the authors.

However, continuing follow-up in the cohort will determine whether in utero DDT associations with breast cancer are observed for cases diagnosed in the future, in patients of older ages.

The authors have disclosed no relevant financial relationships.

J Clin Endocrinol Metab. Published online June 16, 2015. Abstract

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