Their Breast Guess by Ronnie Cohen

Marin Women’s Study links sky-high cancer numbers to sky-high hormone therapy

Breast Cancer

Marin County could be on the brink of losing its grave distinction as the world’s breast cancer capital, thanks to droves of women abandoning a drug that pharmaceutical manufacturers and doctors once marketed as a miracle way to combat menopausal symptoms and postpone aging.

In 2002, heeding public-health warnings that hormone therapy could give them breast cancer, more than 57 percent of Marin women quit taking the prescription medication. At about the same time, a study released last week shows breast cancer rates for non-Hispanic white Marin women ages 50 and older slid a whopping 33 percent—dipping below the state’s average for the first time in a decade.

The initial results from the Marin Women’s Study add weight to other statewide and national investigations showing that when women stopped taking estrogen and progestin therapy, striking reductions in breast cancer incidence followed.

“This is compelling evidence,” says Rochelle Ereman, a Marin County epidemiologist and principal investigator for the study published this month in BMC Public Health, a peer-reviewed online journal. “This shows that the drop in estrogen and progestin led to a dramatic drop in the breast cancer rates.”

Launched in 2006 in hopes of solving the mystery of why Marin women were at one point 38 percent more likely than other urban California women to be diagnosed with breast cancer, the Marin Women’s Study has enrolled more than 14,000 women volunteers at mammography centers. The BMC Public Health report examines survey results from 1,083 participants. It is the first in a series of reports researchers expect to write analyzing respondents’ answers to 87 wide-ranging questions—from when the women began to menstruate, when and if they bore children and breastfed, how much they drink alcohol, if they used lawn-care services, birth-control pills, fertility drugs or hormone-replacement therapy.

Ereman was filing early completed questionnaires when she noticed a recurrent theme. Many of the women said they had stopped taking combination hormone therapy. An analysis of the data shows that between 2001 and 2004, half of non-Hispanic white Marin women 50 years and older who had been taking so-called combination hormone therapy stopped. During the same period, breast cancer rates for the group fell 33.4 percent.

The report says the drop spared some 50 Marin women a year from the disabling, disfiguring and emotionally wrenching diagnosis of breast cancer.

“This type of change in a risk factor is almost unheard of,” Ereman says. “We’re not going to see dramatic changes in other breast cancer risk factors—alcohol use, menarche or child-bearing. This answers a piece of the puzzle of why Marin’s rates are high.”

Marin’s breast cancer rates for white women ages 50 and above dropped so significantly in 2003 and 2004 that they were lower than the state’s average. The rates climbed back up from 2005 until 2007, the most recent years available, but remained lower than they had been through much of the 1990s. Investigators are anxiously awaiting new data to see if the trend holds.

For reasons it took researchers years to tease out, Marin served as a so-called canary in a coal mine for combination hormone therapy and breast cancer. Women in this mostly white, affluent county of 250,000 were more likely to take combination hormone therapy, and they were quick to abandon it in 2002, after a large national study called the Women’s Health Initiative exposed myriad health risks from the treatment.

Coming on the heels of other studies that reported similar though less dramatic findings, the precipitous drop in Marin women’s hormone therapy use followed by the stunning drop in breast cancer rates did not shock Janice Barlow, executive director of San Rafael-based Zero Breast Cancer. What does surprise her, she says, is that more has not been done to stop pharmaceutical companies from marketing combination hormone therapy eight years after the Women’s Health Initiative concluded it harms significantly more women than it helps.

There just wasn’t enough outrage over hormone-replacement therapy when the Women’s Health Initiative came out. Neither the American Cancer Society nor the American Association for Cancer Research has taken a position. They’re avoiding it because it’s political. Nobody’s coming out strongly against taking hormone-replacement therapy.

To me, the message from a public health perspective is to get women and physicians to stop taking and prescribing hormone-replacement therapy.

Where doctors once prescribed the therapy routinely to middle-age women whether they complained of menopausal symptoms or not, most doctors now recommend the therapy only to relieve hot flashes and other problems associated with a drop in estrogen levels as a result of menopause. Furthermore, physicians nowadays are more likely to prescribe the treatment for a limited time—rather than from middle age until death, as doctors did before.

In 1998, more than 21 percent of white Marin women ages 50 and above took combined hormone therapy. By the years 2006 and 2007, the number shrank to 6.7 percent.

A San Anselmo woman says her doctor reassured her two years ago that she could safely take combination hormone therapy. The 52-year-old San Anselmo mother who spoke on the condition of anonymity says she was not tuned into news reports about menopausal treatments in 2002, years before she began to experience symptoms, when researchers halted the combined hormone therapy arm of the Women’s Health Initiative because women taking the drugs were getting sick.

The San Anselmo mother says her physician put her on hormone therapy after she complained of hot flashes and difficulties controlling her emotions. She said the physician told her hormone therapy would be good for her heart, her bones and might protect her against Alzheimer’s.

There is evidence that combined hormone therapy protects against broken bones, but there is no evidence that it wards off Alzheimer’s. Furthermore, the Women’s Health Initiative, in comparing women taking combination hormone therapy to those taking placebos, found those on combination therapy were 26 percent more likely to develop breast cancer, 29 percent more likely to have a heart attack and 41 percent more likely to have a stroke.

“I took it because I had a change in personality,” the San Anselmo mother says. “I basically had no patience with anyone, and I was snapping and yelling at my children and alienating my daughter. I guess I made the decision that I would rather risk breast cancer than to drive my daughter away.”

Keriman Getchell, 70, of Tiburon, wishes she had the wisdom of the Women’s Health Initiative and the Marin Women’s Study before she began taking estrogen and progestin. When she complained about hot flashes, her doctor put her on hormone therapy. Getchell took the pills for 17 years, until 2002, right about the time the results of the Women’s Health Initiative were released, when she was diagnosed with breast cancer.

While her husband was bedridden with Parkinson’s disease, Getchell underwent a double mastectomy, chemotherapy and radiation.

I was burning like someone put me in a 500-degree oven. So my gynecologist gave me this medicine. Doctors didn’t know either. They thought it was good for you.

I wasn’t blindly taking these medicines. My doctor said: ‘Don’t worry about it. These are the new medicines. If you take estrogen with progestin, it protects you from cancer.’

Ironically, researchers believe it is the progestin—added to the estrogen therapy in the 1980s, when Getchell began taking the drug, to protect women against uterine cancer—that leads to breast cancer.

In a cruel twist, in the 1970s, endometrial cancer rates began spiking among Bay Area women. Turns out women here had been taking more estrogen than women elsewhere. After researchers connected endometrial cancer with the estrogen, Bay Area women largely abandoned the hormone therapy. Then the uterine cancer rates —particularly elevated in Marin—dove.

In response, the pharmaceutical industry repackaged hormone therapy to give women a second hormone, progestin, along with estrogen. Progestin protects women with intact wombs against endometrial cancer. What physicians did not initially realize was that progestin exposes women to increased risk of heart disease, stroke and breast cancer.

Researchers continuing to follow the Women’s Health Initiative participants also have reported an increased risk of lung cancer, particularly in smokers, among women who took the combination therapy. “Breast cancer may be only the tip of the iceberg in terms of hormone-replacement therapy,” Barlow says.

In the 1990s, Marin breast cancer survivors, some of whom subsequently died from the disease, formed the nonprofit Marin Breast Cancer Watch, now called Zero Breast Cancer, to examine why Marin women were so much more likely to develop breast cancer than women elsewhere. They looked for the cause in the air, the ocean, on Mount Tamalpais, in the oil refinery across the bay, in pesticides, fertilizer, on their clothes, their lawns, their pets. They looked for a smoking gun but found none.

They did look inside their medicine cabinets at birth-control pills and hormone-replacement therapy. But researchers assured them that these pharmaceuticals were not the culprit.

What those researchers failed to realize and epidemiologist Ereman caught is that women in Marin were less than half as likely as their counterparts in other parts of the state to have had a hysterectomy. Women with hysterectomies who take menopausal therapy take estrogen alone. Consequently, although Marin women were no more likely than other California women to be on hormone therapy, they were more likely to be taking estrogen plus progestin, leading to more breast cancer cases.

Researchers say it is too early to tell if removing so many doses of combination hormone therapy from Marin will permanently remove the excess cases of breast cancer in Marin. “I think it tells us an important piece of the puzzle,” says Fern Orenstein, a breast cancer survivor, founding member of Marin Breast Cancer Watch and one of the study’s authors. “But the puzzle is bigger.”

In addition to having mammography patients fill out questionnaires, the Marin Women’s Study, funded by the federal Centers for Disease Control, has been collecting saliva samples and plans to analyze the bio-specimens to learn more about the causes of breast cancer. “We’re going to put these pieces of the puzzle together in the next few years,” Ereman says.

“The Marin Women’s Study will continue to try to come up with additional leads to help drive the rates even lower,” says Dr. Christopher Benz, an oncologist and one of the study authors. “This is just a first report, and there’s a lot more that’s going to come out.”

As far as whether hormone therapy rules out an environmental smoking gun causing breast cancer, Barlow says no one has yet begun a serious hunt for environmental causes. “We haven’t really studied the environment,” she says. “We haven’t had the tools.

“I don’t want people to go away like this is the answer.”

Everyone involved in the research agrees that hormone therapy was one part of the reason for Marin’s elevated rates. They all also agree that breast cancer is a complicated disease stemming from an interaction of environmental, genetic and lifestyle risk factors.

“It was so much easier when people could go around and say—’It’s the environment,’ ” Barlow says. “I just don’t think you can do that anymore.”

Pacific Sun

May 28, 2010