Breast cancer and the environment: Women's exposures early in life could unlock mysteries

About 100,000 blood vials have been collected from three generations of women in a study that began in Berkeley, Calif., in 1959.
Paul Chinn, San Francisco Chronicle

 

By Lindsey Konkel
Environmental Health News
Part 1 of 2

 Feb. 26, 2013

 
Deep in a laboratory freezer, 100,000 vials of blood have been frozen for the better part of five decades.

For scientist Barbara Cohn, it’s a treasure trove. Collected from more than 15,000 San Francisco Bay Area women after they gave birth in the 1960s, each vial of blood holds a woman’s lifetime of secrets.

Nina Holland, director of a Berkeley, Calif., biorepository, describes blood tests to women participating in a study investigating links between environmental exposures and diseases.
Paul Chinn, San Francisco Chronicle

Scientists say these vials could help them unravel one of the most enduring medical mysteries: Why do some women, with no family history, develop breast cancer?

The blood bears the chemical signature of environmental pollutants, some long banned, that the women were exposed to decades ago. Cohn, who directs the research in Berkeley, Calif., believes these early-life exposures may hold the key to understanding a woman's risk of breast cancer today.

The women's blood is being tested for traces of dozens of pollutants – used by industry and found in many consumer products – that can impersonate estrogen and other hormones. The theory is that early exposure to these chemicals, even before birth, inside the mother’s womb, may fundamentally alter the way that breast tissues grow, triggering cancer decades later.

Cancer patients and their doctors have long puzzled over what factors in a woman’s environment may raise her risk of breast cancer. One of every eight women in the United States is diagnosed with breast cancer during her lifetime, with more than 232,000 new cases diagnosed yearly, according to the American Cancer Society. Only 5 to 10 percent can be accounted for by genetics; other known risk factors include age, obesity and low physical activity.

One of every eight women in the United States is diagnosed with breast cancer during her lifetime, with more than 232,000 new cases diagnosed yearly, according to the American Cancer Society. Earlier this month, a science advisory panel urged the federal government to fund more projects aimed at uncovering the environmental causes of breast cancer because eliminating these factors may provide the greatest opportunity to prevent it.

It’s particularly vexing for scientists because it’s difficult to unlock a woman’s exposures during her most critical times for breast development: in the womb and during puberty and pregnancy.

“As researchers looking at adult outcomes of disease processes such as breast cancer, one of the biggest challenges we face is trying to get a handle on prenatal exposures and what is going on in the prenatal environment,” said Shanna Swan, an environmental health scientist at Mount Sinai School of Medicine in New York.

Many scientists have been looking for connections between various environmental exposures and the disease – with mixed results. Some findings suggest links to a few chemicals, including the banned pesticide DDT. But others have found no link.

Lab manager Jessica McFadden pulls out a rack of blood samples stored in a liquid nitrogen tank.
Paul Chinn, San Francisco Chronicle

For example, experts from the American Cancer Society, reviewing previous studies, in 2002 found no association between breast cancer and chlorinated chemicals including DDT.

And in 2011, an institute of the National Academies of Sciences reported “a possible link” between breast cancer and some common ingredients of vehicle exhaust, benzene and 1,3-butadiene. But the report said the jury is still out for most other widespread chemicals, such as pesticides, ingredients of cosmetics and bisphenol A (BPA).

Nevertheless, absence of evidence isn’t evidence of absence, said Elizabeth Ward, National Vice President of Intramural Research at the American Cancer Society. Many of the biggest risk factors remain unknown, she said.

The problem with most studies is that they measured levels of chemicals in women later in life, after they were diagnosed with cancer, not during periods when the breast is most susceptible, said Suzanne Fenton, a reproductive toxicologist at the National Institute of Environmental Health Sciences in North Carolina.

“The research doesn’t prove that the link doesn’t exist or that these chemicals are safe for the breast,” Fenton said. “It shows that we may not have been asking the right question.”

Epidemiologist Barbara Cohn, director of the Child Health and Development Studies in Berkeley, has been working with the study group for 17 years.
Public Health Institute

The strongest evidence for this link emerged decades ago. Researchers first suspected that hormone-mimicking chemicals may play a role in breast cancer when they discovered that women who took the anti-miscarriage drug diethylstilbestrol (DES) – a potent form of estrogen prescribed for pregnant women from 1938 until 1971 – had about a one-in-six lifetime risk of developing breast cancer. The risk is 1 in 8 for all women. In addition, their daughters, who were exposed to DES in the womb, developed breast cancer at about two times the rate of unexposed women.

Lab manager Jessica McFadden draws a sample from a vial of blood from a woman in the multi-generation study.
Paul Chinn, San Francisco Chronicle

Some scientists say timing of exposure may be the single most important factor when evaluating how chemicals may contribute to breast cancer risk.

The breast is a complex tissue that undergoes several important periods of development and remodeling over the course of a woman’s life. During these periods – before birth when the bud of the mammary gland forms, at puberty when breast cells are rapidly growing and dividing and during pregnancy as the mammary gland transitions to lactation – the breast may be especially susceptible to outside chemicals.

When breasts are exposed to hormone-like substances during those sensitive times, it could “influence susceptibility of the tissue to carcinogens or other hormonal stimuli that could increase cancer risk later on,” said Ruthann Rudel, a researcher at the Silent Spring Institute, a nonprofit research group in Massachusetts, and lead author of a 2011 review.

Cohn and colleagues at the Public Health Institute are using the blood samples of more than 2,000 women who enrolled in the Child Health and Development Studies in the 1960s to investigate exposures during two of these critical periods, pregnancy and postpartum. The women were members of the Kaiser Permanente Health Plan in the Oakland, Calif., area who gave birth between 1959 and 1967. [Editor's note 2/25/2013: Correction in number of women.]

The scientists recently reported that women who had high levels of a certain PCBs in their blood shortly after giving birth were three times more likely to develop breast cancer later in life than women with lower levels. Because PCBs break down very slowly in the body, a woman’s blood levels postpartum may also predict the PCB levels in her blood during earlier periods of her life, such as puberty, Cohn said.

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