Big Drop Is Seen in Breast Cancer

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Reversing Trend, Big Drop Is Seen in Breast Cancer

 

NYTimes

By GINA KOLATA

Published: December 15, 2006

 

Rates of the most common form of breast cancer dropped a startling 15

percent from August 2002 to December 2003, researchers reported yesterday.

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The reason, they believe, may be because during that time, millions of

women abandoned hormone treatment for the symptoms of menopause after

a large national study concluded that the hormones slightly increased

breast cancer risk.

 

The new analysis of breast cancer rates, by researchers from the M. D.

Anderson Cancer Center in Houston and presented at a breast cancer

conference in San Antonio, was based on a recent report by the

National Cancer Institute on the cancer's incidence.

 

Investigators cautioned that they would like to see the findings

confirmed in other studies, including, perhaps, in data from Canada

and Europe, and they would like to see what happens in the next few years.

 

" Epidemiology can never prove causality, " said Dr. Peter Ravdin, a

medical oncologist at the M.D. Anderson center and one of the authors

of the analysis.

 

But, he said, the hormone hypothesis seemed to perfectly explain the

data and he and his colleagues could find no other explanation.

 

Donald Berry, head of the division of quantitative science at the

cancer center and the senior investigator for the analysis, called the

connection between the drop in rates and hormone use " astounding. "

 

Over all, for women of all ages and all breast cancer types, the

incidence of the cancer, the second leading killer of women, dropped

by 7 percent in 2003, or about 14,000 cases, the researchers said. It

was the first time that breast cancer rates had fallen significantly,

something experts said was especially remarkable because the rates had

slowly inched up, year by year, since 1945.

 

But the decrease was most striking for women with so-called

estrogen-positive tumors, which account for 70 percent of all breast

cancers.

 

In July 2002, the Women's Health Initiative, a large clinical trial

looking at the use of one menopause drug, Prempro, made by Wyeth,

found that women taking the drug had slightly higher breast cancer

rates. The study's findings were a shock to many women and their

doctors. Until then, many had assumed that Prempro simply replaced the

lost hormones of youth. Within six months, the drug's sales had fallen

by 50 percent.

 

Scientists knew that hormones could fuel the growth of

estrogen-positive tumors, which carry receptors for estrogen on their

cell surfaces. The hypothesis is that when women stopped taking

menopausal hormones, tiny cancers already in their breasts were

deprived of estrogen and stopped growing, never reaching a stage where

they could have been seen on mammograms.

 

Other cancers may have regressed, making them undetectable. And,

possibly, without hormones, cancers that would have gotten started may

never have grown at all.

 

" This could well be the study of the year in cancer, " said Dr. Otis

Brawley, director of the Georgia Cancer Center at Emory University. He

added that it also might help explain why breast cancer rates were

lower for black women than for white women — blacks, he said, were

less likely to use hormones for menopause.

 

Dr. Brawley also said the findings might explain why cancer in black

women was more lethal. Hormone-initiated cancers, he said, might be

less deadly than those that arise on their own.

 

Candace Steele, a Wyeth spokeswoman, said in an e-mail message that

" breast cancer is a complex disease and the causes are not known.

 

At this point, she said, " it is simply inappropriate to make any

speculative statements " based on the analysis.

 

And, she added, " clearly, more studies are warranted. "

 

Dr. Berry said that the biggest effect overall was seen in women ages

50 to 69. That, he added, is the group most likely to have been taking

menopausal hormones. In them, the incidence of breast cancer,

including the type that grows in response to estrogen and the one that

does not, fell by 12 percent in 2003, the latest year for which data

is available.

 

The findings of the new analysis were supported by a separate study in

California. That study, published in the Nov. 20 issue of the Journal

of Clinical Oncology, found an even bigger drop in rates in that state

and a correspondingly bigger drop in hormone use starting in July 2002.

 

Other researchers, who saw Dr. Berry's analysis in advance of its

presentation yesterday, said they found the hypothesis convincing.

 

Susan Ellenberg, a professor of biostatistics at the University of

Pennsylvania, said the work was provocative. And, she added, " I

certainly don't see any obvious thing that says, `Oh, this can't be

right,' or any obvious flaws. "

 

Until 2002, as many as a third of American women over age 50 were

taking menopausal hormones. The drugs could relieve symptoms like hot

flashes, and were thought to protect against heart disease. Because

the pills were known to slow bone loss, some women used them to

prevent osteoporosis. Some women and doctors also believed, without

any good evidence, that the pills could keep skin youthful, preserve

memory and make women energetic.

 

The use of estrogen to treat menopause took off in 1966, when a

doctor, Robert Wilson, wrote the best-selling book " Feminine Forever "

and flew across the country promoting it. He insisted that estrogen

could keep women young, healthy and attractive. Women would be

replacing a hormone they had lost at menopause just as diabetics

replace the insulin their pancreas fails to make.

 

Before long, the menopause drugs, and in particular Prempro, from

Wyeth, a combination of estrogen and progestins, became one of the

most popular drugs in history.

 

The reversal of fortune came in July 2002 when the Women's Health

Initiative was halted. Its accumulating data indicated that Prempro

was associated with a slight increase in breast cancer and in heart

attacks, strokes and blood clots. The drug slightly decreased the risk

of hip fractures and colon cancer, but those benefits were not enough

to overcome its risks, the researchers said. Health authorities

cautioned that similar pills must be regarded as having the same risks

as Prempro until proven otherwise.

 

The very next year, 2003, the National Cancer Institute reported

recently, there was a huge decline in breast cancer incidence. It was,

Dr. Ravdin said, the largest decline for a single cancer in a single

year that he was aware of. He and his colleagues wondered what was

going on. The cancer kills an estimated 40,000 women a year and any

decline in incidence can be important.

 

" We looked at all the possible explanations, " Dr. Berry said. He

ticked them off: less mammography screening. But there was no sign of

that. Increased use of drugs like tamoxifen that can prevent breast

cancer; no evidence of that.

 

" There was some notion that it might be statins, but that was

essentially debunked, " Dr. Berry said.

 

After July 2002, Dr. Berry said, the rate " dropped each month and it

is exactly where you would expect it to be " if the declining use of

menopausal hormones were the reason.

 

Dr. Barnett Kramer, the associate director for disease prevention at

the National Institutes of Health, said that hormones were certainly

the most plausible explanation for such an immediate effect on

incidence. Most breast cancer is fueled by estrogen and studies have

found that removing estrogen, with drugs like tamoxifen that block the

hormone, sharply reduces breast cancer rates within a year.

 

That was also the conclusion of Christina Clarke, an epidemiologist at

the Northern California Cancer Center, and her colleagues, when they

analyzed the cancer's rates in California. The investigators used data

they had collected for a National Cancer Institute's program and data

from Kaiser Permanente, the health insurer.

 

Dr. Clarke said that they had data through 2004 and so could ask

whether the decrease in cancer incidence in 2003 continued the next

year. It did, she said, although it slowed somewhat, as might be expected.

 

The investigators found that the breast cancer incidence fell even

more in California than in the rest of the country — the overall drop

was 11 percent in 2003, compared with 7 percent nationally. And, Dr.

Clarke said, more women in California also had been using hormone

therapy than women in other states.

 

Kaiser Permanente's prescriptions for hormone combinations like

Prempro fell by two-thirds in 2003 and prescriptions for estrogen

alone dropped by one-third, Dr. Clarke and her colleagues reported.

(Estrogen without progestin can cause cancer of the uterine lining so

should only be used by women whose uteruses have been removed. While

there is some question about whether estrogen alone increases breast

cancer risk, the Women's Health Initiative did not find such an effect.)

 

The heaviest users of hormone therapy were women in affluent places

like Marin County, where high breast cancer rates had long troubled

women and researchers. Women in those areas also largely abandoned the

treatments after the 2002 report and their cancer rates declined

accordingly, Dr. Clarke said.

 

Dr. Marcia Stefanick, a professor of medicine at Stanford University

and chairwoman of the steering committee for the Women's Health

Initiative, said she found the hormone argument persuasive and felt it

helped clear up the mystery in Marin County.

 

" Everyone kept saying, What is it? What's in the environment? " she

said. Now, she said, it is becoming clear. " The best explanation is

hormone therapy. "