Here's the Philadelphia Inquirer Breast Cancer story:
Breast-cancer breakthrough: Drug cuts rates in study
By Marie McCullough
INQUIRER STAFF WRITER
A landmark study has cut breast cancer rates by nearly half among healthy women at increased
risk for the dreaded disease, showing for the first time that the drug tamoxifen can prevent breast
cancer.
Letters announcing the breakthrough have gone out to the 13,000 women in the United States
and Canada who kept on with the Breast Cancer Prevention Trial despite controversy over its
risks and benefits.
''Based on the most recent analysis of the data, this is now the first study in the world to show
that a drug can reduce the incidence of breast cancer,'' the letter says. ''Specifically, the study
has shown that tamoxifen is effective in reducing the rate of breast cancer by an estimated 45
percent for . . . women at increased risk.''
''I'm just thrilled. Wow!'' Patricia Lorah, 45, of Reading said yesterday as she ripped open her
letter. ''My mother and grandmother died of breast cancer. This is almost overwhelming.''
Her excitement was echoed by other area women who reacted with words such as ''fantastic,''
and ''terrific.''
Researchers would not discuss the results, which are to be released Wednesday at a news
conference.
The massive, $68 million study - one of the largest cancer prevention trials ever undertaken -
was launched by the National Cancer Institute in 1992. Women at higher risk of cancer because
of family history, precancerous breast lesions or age were randomly assigned to five years on
either dummy pills or tamoxifen, a widely used breast cancer treatment drug made by
Wilmington-based Zeneca Pharmaceuticals. A code masked their therapy so no one would know
which they were taking.
The study had been expected to continue blinded for two more years, but the dramatic findings
prompted researchers to unmask the findings so all the women could choose to take tamoxifen.
To break their code, women will go to the study physicians at 270 medical centers.
Helene Wilson, 48, of North Wales, said, ''I'm hoping I was on tamoxifen, but if I was in the
placebo arm, I am going to ask my physician to put me on tamoxifen because I really believe in it.
I think the 45 percent reduction is fantastic.''
While the letter does not specify how many breast cancer cases were averted, it says the
reduced rate ''means that in a group of women similar to the [study] population, rather than 100
breast cancers developing in the first 3 1/2 years after taking tamoxifen, there would be 55 cases
of breast cancer.''
Based on those numbers, it appears that tamoxifen reduced the rate of expected breast cancers
from 1 in 130 women to 1 in 236 women during the period.
Medical recommendations for using tamoxifen to prevent cancer are still being developed, the
letter says. But it notes there is no evidence that taking the drug for more than five years is
beneficial.
Researchers are still analyzing the data, the letter says, to see whether subgroups of women
benefited more than others, and to better understand the potential risks of using tamoxifen as a
preventive medication. Tamoxifen is associated with increased risks for cancer of the uterine
lining and for dangerous blood clots that can lodge in the lungs.
Leslie Ford, the National Cancer Institute official overseeing the trial, predicted four years ago
that if 16,000 women were recruited, tamoxifen would be expected to prevent 120 to 125 breast
cancer cases, while producing 58 to 80 new cases of uterine cancer - which is far easier to detect
early and cure than breast cancer.
According to the letter, the overall study data ''show that the rate of these risks does not
exceed what has been originally predicted for the study.''
Tamoxifen's risks brought the study under intense scrutiny and criticism. The National Women's
Health Network in Washington argued that the study was disease substitution, not disease
prevention.
Enrollment in the trial was temporarily suspended and congressional hearings were held in 1994
after the disclosure of four unreported uterine cancer deaths in a study of breast cancer treatment
using tamoxifen. Those hearings also looked into reports that the coordinator of the prevention
trial, University of Pittsburgh surgeon Bernard Fisher, was slow to address research problems in
studies known as the National Surgical Adjuvant Breast and Bowel Project.
Most women stayed in the prevention trial through those difficult days, taking their daily pills
with doses of faith and hope.
''I got a lot of grief from my friends and family for getting in this study,'' Lorah recalled. ''They
thought I was crazy. But I had watched my mother die at a young age of metastatic breast
cancer. I couldn't see why anyone would not want to participate.''
Fern Maklin, 49, of Newtown, Bucks County, said, ''I never considered dropping out. My
thoughts were more like, 'Maybe I'll save my child's life and my own and other people's.' ''
Even Barbara Walsh, 52, of Newtown Square, has no regrets. She spoke Friday from Paoli
Memorial Hospital, where she was recovering from a double mastectomy and reconstructive
surgery. It turns out she was on a placebo. Her code was broken in February when she was
diagnosed with breast cancer.
''People say they're sorry that the trial didn't help me, but if I hadn't been in the trial I might not
have found this cancer as fast,'' Walsh said. ''I'm not sorry. I thought from the start that it might
not help me, but it might help my daughter or someone else in my family.''
Women in the study underwent intensive medical monitoring that involved breast exams, blood
tests, endometrial biopsies and mammograms. They filled out detailed questionnaires on lifestyle
and mental health. They had frequent meetings with their own and study doctors.
They will continue to be followed for at least two years.
The achievement marks a turning point in the battle against breast cancer. While mortality rates
have been falling thanks to earlier detection and better treatment, incidence rates continue to
climb. More than 180,000 new cases of breast cancer will be diagnosed this year. A growing
number of women will discover through genetic testing that they are predisposed to breast
cancer. Yet until now, the only way to prevent it was to remove healthy breasts.
Indeed, that's what Lorah's gynecologist suggested she do in 1993 after a large, benign lump
was removed from her breast.
''When I said no, he suggested the study,'' she said.
Tamoxifen, used to treat breast cancer for 20 years, has been shown to prevent recurrence of
the disease, halt microscopic spread and lower mortality rates.
It works like a weak version of estrogen, the powerful hormone that acts on cells throughout
the body. If breast cancer cells are present in the body, tamoxifen slips into their estrogen
receptors and locks up the cells, thus blocking estrogen from stimulating their growth and
proliferation.
Like estrogen, tamoxifen has both good effects - notably, reducing the risk of osteoporosis
(bone loss) and heart disease - and bad effects. Narberth oncologist Marisa Weiss says in her
book Living Beyond Breast Cancer that one woman in a hundred is likely to develop a blood
clot in the lungs, and two women in a thousand are likely to develop uterine cancer. Tamoxifen
also can produce uterine bleeding, hot flashes, vaginal dryness, weight gain, temporary nausea
and mood swings.
Lorah, for example, suffered such severe headaches and uterine bleeding that she had to stop
taking the pills just shy of the five-year endpoint.
Critics of the trial say they are eager to hear more about the tradeoffs of therapy.
''If this turns out to be a good risk-benefit ratio for some women, that will be good news,'' said
Cindy Pearson, executive director of the National Women's Health Network. But it's
''imperative for researchers to tell women what . . . they know about the cost of this benefit. Did
any women die of anything caused by tamoxifen?''
The women who put their bodies on the line say they are proud of their contribution.
''We're like pioneers,'' Wilson said. ''We feel like we've made a difference.'' |
