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 Bay Area women after they gave birth in the 1960s, each vial of blood holds a woman's lifetime of secrets.
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 is directing the Berkeley-based research study, believes these early-life exposures may hold the key to understanding a woman's risk of breast cancer today.
Cohn is testing the blood of the women for traces of dozens of pollutants — used by industry and found in many consumer products — that can mimic estrogen and other hormones. The theory is that early exposure to these chemicals, even before birth, in 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 out of every eight women in the United States will be 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.
Ida Washington of San Leandro is participating in the study directed by Cohn. Her mother was diagnosed with breast cancer nearly forty years ago. Now 52, Washington was just a teenager when the lump was found on her mother's left breast. In the years that followed, as her mother's cancer went into remission, Washington began to wonder what caused it. "My mother didn't smoke, she didn't drink. Breast cancer didn't run in the family," she said.
Ida's mother, Willie Mae Washington, now 92, participated in the first generation of the scientific study that Cohn and her colleagues are continuing. In 1959, under the direction of Jacob Yerushalmy, a professor of biostatistics at UC Berkeley, the first participants were enrolled through their health care provider, Kaiser Permanente. Over the years, many study families stuck with Kaiser. Having all study participants initially on a single health plan with its own clinics and hospitals helped researchers gather detailed information about them.
Ida Washington remembers filling out questionnaires and having body measurements taken at doctor's visits during childhood and adolescence. "I never thought much about it," she said. "The tests were just part of the routine." It wasn't until several years later, when she was invited to participate in the study, that she realized what it was all for.
Washington works as a claims assistant for Kaiser Permanente in Oakland. She has a thirty-year-old son that she hopes will be asked to participate in a men's follow-up study. Her mother, who worked as a nursing aide in convalescent and private homes at the time, no longer remembers when she was approached about the study or why she joined. "I think shortly after Ida was born," she said. "I had three older children. Ida was my baby."
Like Washington, study participant Laurie Havas, also 52, had no idea as a child that she was part of a multigenerational research project that her mother had joined before her birth. Havas' mother died of pancreatic cancer when Havas was 21. When she got a letter in the mail asking her to participate in a follow-up, she knew it was something she had to do. "I am doing it for myself and my mother. I am continuing her legacy. It makes me feel closer to her," said Havas, who lives in Pleasant Hill.
The blood that women provided in the 1960s was frozen and now resides at a storage facility in Reston, Virginia. Cohn, director of the Child Health and Development Studies and Three Generations follow-up study, rations serum from the archived vials sparingly. When the vials are gone, so is the information — and potential — that they hold. New blood and urine samples, provided by the second generation of women, now in their late forties and early fifties, as well as their daughters, are processed and stored at a state-of-the-art biorepository on the Cal campus. "These women are a national treasure," said Cohn, an epidemiologist who has been involved with the cohort for the past seventeen years. "They hold the key to understanding the risks" of breast cancer.
For decades, 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.
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."
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 one in eight 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.
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 Oakland-based Public Health Institute are using the blood samples of more than 2,000 women who enrolled in the Oakland-area study in the 1960s to investigate exposures during two critical periods: pregnancy and postpartum.
The scientists recently reported that women who had high levels of certain industrial chemicals known as polychlorinated biphenyls (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 levels of PCBs in her blood during earlier periods of her life, such as puberty, Cohn said.
Banned in the United States 35 years ago, PCBs persist in the environment and accumulate in food webs. Nearly every US resident still has detectable levels of PCBs in his or her blood.
In a previous study, Cohn and her colleagues demonstrated that age at time of exposure matters for other chemicals, too. In the same group of women, they found that those with high blood levels of DDT shortly after giving birth were five times more likely to develop breast cancer before age fifty than the women with the lowest blood levels. Other studies measuring DDT exposure later in life found no link.
Cohn can't say for sure that the associations she and her colleagues observed between breast cancer and PCBs or DDT were not due to some other factor. "No human study can be definitive," said Cohn. "It's impossible to measure every single exposure pertinent to breast cancer."
Laboratory research may bear out a definitive link. In lab animals, scientists can test the effects of various levels and mixtures of chemicals, which would be unethical in humans. "The work we do in humans helps frame the type of questions to be answered by animal studies," Cohn said. Such collaboration, she said, "is critical to advancing our knowledge."
Studies in mice and rats suggest that exposure to bisphenol A (BPA) — which is used to make hard plastics, liners of food cans, and some paper receipts, and is found in most human bodies — and other endocrine disruptors in the womb not only alters the structure of the breast, but the way that the tissues communicate with one another and receive hormonal signals from other parts of the body. "BPA sets the thermostat in a more sensitive way so the mammary gland has more sensitivity to estrogen, and the breast tissue now exhibits an exaggerated response to the hormone. It sees a little bit of estrogen and now thinks it is a lot," said Dr. Ana Soto, a cancer researcher at Tufts University School of Medicine in Massachusetts. And the body can't tell the difference between synthetic estrogen mimics and natural estrogens.
BPA and other chemicals also may play a role in breast density — a known risk factor for breast cancer. A preliminary study by University of Wisconsin researchers found that women with higher blood levels of BPA had denser breast tissue than women with low levels.
With so much uncertainty about environmental risk factors, these issues remain largely absent from major breast cancer awareness campaigns. "Despite billions spent in the name of breast cancer, we still don't know enough about the causes," said Karuna Jaggar, executive director of Breast Cancer Action, a San Francisco-based advocacy organization and movement watchdog.
While decades of research have failed to turn up strong, environmental risk factors, Cohn is optimistic that scientists are now on the right track. "The science is playing catch up; we have learned from what we didn't learn," she said.