An association between long-term use of estrogens by postmenopausal women and a doubled risk of breast cancer has been reported by California scientists.
They found that a woman who starts at age 50 to take the drug daily for three years increases her risk of getting the disease by age 75 from 6 percent to 12 percent.
The woman would have been taking pills containing 1.25 milligrams of estrogen -- the dose in 56 percent of the nine million prescriptions filled in 1979 for Premarin, the leading brand. The prescriptions filled for other brands totaled 4.5 million.
The study, published in the April 25 Journal of the American Medical Association, is the first to confirm the fear in a 1976 report that a link between postmenopausal estrogens and breast cancer was "a definite possibility."
In addition, one of the authors of the 1976 report told a reporter that the new study "has to raise the level of concern about all estrogen-containing drugs, including contraceptives."
Emphasizing that birth control pills have not been "adequately evaluated," the scientist, Dr. Robert N. Hoover of the National Cancer Institute, said, Contraceptives haven't been noted to be associated with excess breast cancer risk -- yet."
Postmenopausal estrogens are prescribed mainly to prevent certain uncomfortable symptoms of the decline in natural production of the hormones by the ovaries that starts with the onset of menopause.
For the new study, the sites were two Los Angeles area retirement communities with a combined population of 30,000. Charts and records from their extensive medical care facilities and pharmacies were available.
Starting in 1971, a team of seven researchers led by Dr. Ronald K. Ross of the University of Southern California isolated 138 residents -- all affluent whites -- in whom breast cancer was diagnosed between October 1971 and July 1977, whose age when diagnosed was between 50 and 74, who had no previous history of breast malignancy and who were postmenopausal.
The scientists then paired the 131 women willing to be interviewed with 262 "controls" -- women in the same communities who had not had breast cancer but who matched them in age and other key attributes.
Finally, the scientists interviewed the 393 women and searched the records, which included all prescriptions written for estrogens from 1964 to 1975.
The key finding of a doubled incidence of breast cancer after three years of taking 1.25 mgs of estrogen a day troubled the scientists.
"The benefits of estrogen therapy at this dosage level would need to be extremely great to warrant such risk," they wrote. At lower dosages, such as 0.625 mg or even less, they said, "the ratio of costs to benefits is clearly more favorable and the impact of breast cancer risk on that ratio is still unclear."
The scientists were admittedly surprised by another finding: The risk of breast cancer in women whose ovaries were intact was even larger -- 2.5 times normal.
Breast cancer is often fatal. This year, by estimate of the American Cancer Society, it will be found in about 108,000 U.S. women. In addition, 36,000 others will die from it.
The new study, which exonerated all nonestrogen drugs taken by the women who developed breast cancer, is the latest chapter of disillusionment about estrogens.
Starting about 40 years ago, claims were made that regular taking of estrogen tablets not only wouldn't cause breast or other forms of cancer, but would actually prevent it. The claims were based on studies that were later faulted by scientists as poorly controlled.
In the early 1960s, manufacturers, including Ayerst Laboratories, the American Home Products Corp. division that makes Premarin, began massive promotion of such claims to physicians. In addition, some doctors, particularly Brooklyn gynecologist Robert A. Wilson, helped by drug company funds, touted estrogens to the general public as drugs that would keep users "feminine forever."
The first jolt to such claims came in late 1975, the year in which the number of estrogen prescriptions filled was a record 27.7 million. That was more than twice the total for 1979, when manufacturers grossed $61 million.
The jolt was in separate reports by three independent teams of scientists that cancer of the lining of the uterus, called endometrial cancer, occurs 4.5 times to 13.9 times as often in postmenopausal estrogen users as in nonusers.
Unlike breast cancer, however, endometrial cancer is detected and successfully treated with relative ease.
In an editorial published with the California study, two University of Chicago scientists asserted that the study does not show "a significant difference in estrogen use between cases and controls."
Hoover, who heads the Cancer Institute's Environmental Studies Section, acknowledged that the study, like any other, has flaws, but said it appears to confirm the suspicion raised four years ago that long-term estrogen use is related to excess risk of breast cancer.
He said that he and other scientists expect to publish within a few months the results of a study -- much larger than the California one -- of estrogens and breast cancer. He declined to discuss the results.