The Birth of Breast Cancer; Do Adult Diseases Start in the Womb?

Article excerpt

Epidemiologist Dimitrios Trichopoulos, puzzling over why women develop breast cancer, focused on various factors before homing in on a chemical that appeared to operate in a surprising environment many years earlier.

That chemical is the natural hormone estrogen, which may have set the stage for cancer while the women were still in the womb, says Trichopoulos of the Harvard School of Public Health in Boston.

Invasive breast cancer strikes about 180,000 women in the United States each year. It is the most common cancer among U.S. women. Known risk factors, such as a family history of the disease, early menarche, or a first live birth after age 30, account for only a small portion of cases. What's behind the high frequency of this disease in the U.S. population?

Over the years, scientists have blamed and exonerated many factors, including a high-fat diet and abortion, but none has proved the central villain in the story of breast cancer.

New research is drawing attention to the beginning of a woman's life. Trichopoulos and others now believe that some factor within the uterus programs fetal cells for the development of cancer decades later.

"It is a provocative hypothesis-one that needs to be explored further," comments Louise A. Brinton, chief of the environmental epidemiology branch of the National Cancer Institute in Bethesda, Md.

Breast cancer is not the only disease scientists think may be linked to the intrauterine environment. A spate of recent reports suggests that conditions in the womb may play a role in the risk of prostate cancer, heart disease, diabetes, high blood pressure, and other chronic diseases. Such ailments don't appear until the fifth, sixth, or even seventh decade of life.

In the 1980s, Trichopoulos had been trying to figure out why, despite advances in treatment, breast cancer continued to cut a wide swath among U.S. women.

He knew that cells, including mammary cells, face the highest risk of cancer before they become specialized for a specific function. Once a breast cell is specialized for, say, milk production, it is relatively resistant to cancer. Yet some breast cells remain largely immature until puberty or even a woman's first pregnancy. While other researchers looked for the genesis of breast cancer in the teenage years or during a first pregnancy, Trichopoulos went back even further-to the immature breast cells of the fetus.

Trichopoulos also knew that the female sex hormone estrogen fuels the growth of breast cells. Rapidly dividing cells are at greater risk of genetic error, which can lead to cancer. Indeed, some researchers believe that postmenopausal women who take estrogen alone, rather than a combination of hormones, face a higher-than-average risk of breast cancer.

Putting these two ideas together in the April 21, 1990 Lancet, Trichopoulos suggested that high concentrations of estrogen circulating in a mother's womb may increase her daughter's subsequent risk of getting breast cancer.

"If it turns out to be right, it will be an important advance, " Trichopoulos says. "We feel confident that something is happening during the perinatal period."

He is the first to admit that many questions remain about estrogen's role in the womb. Moreover, the hormone is just one of many players that could influence the mammary cells of the fetus, he says.

The first empirical data supporting his theory hit the press 2 years after he proposed it. In the Oct. 24, 1992 Lancet, Trichopoulos, Anders Ekbom, Hans-Olov Adami, both at Uppsala University in Sweden, and their colleagues reported that women who had weighed 8 pounds or more at birth had a 30 percent greater risk of breast cancer later in life (SN: 10/31/92, p. 293).

Other research has suggested that women with higher-than-average concentrations of estrogen in their blood during pregnancy give birth to heavier babies. Because the Swedish study was small, the link between breast cancer and weight at birth could have been due to chance. …