GWEN IFILL: “The Journal of the American Medical Association” released a new study today that finds women on hormone replacement therapy are at greater risk for contracting more aggressive cancers. The study followed nearly 13,000 women between the ages of 50 and 79 for 11 years.
It found the women who took a combination of estrogen plus progestin had an increased risk of death compared to women not on the drugs. The use of hormone replacement therapy to relieve post-menopausal discomfort such as hot flashes has long been the subject of debate.
Dr. Rowan Chlebowski, the study’s lead author, is a medical oncologist at the Los Angeles Biomedical Research Institute. And Dr. Julie Gralow is director of breast medical oncology at the Seattle Cancer Care Alliance and the University of Washington School of Medicine.
Welcome to you both, Doctors. Dr. Chlebowski, you authored this report. At least you were one of the authors. Tell us a little bit about what you found about the increased cancer risk.
DR. ROWAN CHLEBOWSKI, Medical Oncologist, Los Angeles Biomedical Research Institute: Sure. We expanded our observations of the women’s health initiative trial, as you mentioned, of estrogen plus progestin vs. placebo.
Previously, we had reported that the breast cancers were increased and that they were at higher stage. Now we extend that to show that not only good-prognosis cancers, but also aggressive cancers, were increased. And for the first time, we report that deaths from breast cancer are statistically increased as well.
So, this means that cancers that originate on estrogen plus progestin are a real concern.
GWEN IFILL: Does that mean that they’re not diagnosed as soon or that they’re just more virulent in the first place?
DR. ROWAN CHLEBOWSKI: Well, it seems like a little bit of both. The stage is related to the delay in diagnosis. Estrogen plus progestin increases breast density. It acts like a veil over the breast, so it’s harder to see the tumors, yet they’re still growing. So, that’s one factor.
We also think that estrogen plus progestin may have direct effects on the biology of the cancer, making them grow more aggressively.
GWEN IFILL: Dr. Gralow, what is your thought about this after you read this report?
DR. JULIE GRALOW, Seattle Cancer Care Alliance: Well, I think it’s really important that we’re now showing a death.
I think no women should be going on hormone replacement therapy indefinitely after they go through menopause. But I also think it’s important to point out that a companion study that just showed estrogen alone, without the same progestin, really didn’t show an increase in breast cancer. So, there are some other options.
GWEN IFILL: Well, let me ask you about that a little bit. Are we talking about the duration, the amount of time that women are on these drugs, or which drugs they’re on?
DR. JULIE GRALOW: I think it’s probably part of both.
GWEN IFILL: No, go ahead, Dr. Gralow. I will ask you that as question, Dr. Chlebowski.
DR. ROWAN CHLEBOWSKI: Sure.
DR. JULIE GRALOW: I think it’s part of both. The women in this study, on average, were about 62 at the time that they started their hormone replacement therapy. They weren’t women in their late 40s, early 50s who were just starting to get menopausal symptoms. So, it doesn’t really address the age at which they started.
These women were a bit older than most women thinking about going on hormone therapy. Also, I will let Dr. Chlebowski answer the question about the duration. Probably shorter is better if you have to go on these drugs.
GWEN IFILL: Let me ask Dr. Chlebowski to respond to that.
DR. ROWAN CHLEBOWSKI: Sure. One thing is that, for heart disease, it may make a difference to start estrogen plus progestin closer to menopause. But, actually, in this study, we had 5,000 women in their 50s. And the women who started estrogen plus progestin within five years of menopause actually had a somewhat higher risk of breast cancer incidence. Their increase was 41 percent, which was higher than women who entered later.
But it’s true that the estrogen only, which can really be given practically to women who don’t have a uterus, didn’t show this effect. Now, in terms of duration, because the estrogen plus progestin hinders breast cancer diagnosis, it’s really not possible to define a safe interval for at least breast cancer risk. But women should really heed the short-duration FDA labeling indication.
And I think if they have been on it for a year or so, they should talk to their doctor about potentially stopping to see if they still have climacteric symptoms, hot flashes, night sweats that would require them to continue on therapy.
GWEN IFILL: Before I ask Dr. Gralow to respond to that, I want to ask you a little bit about this report, because the study, which began in 1993 — and periodically we get new results from it — have the drugs changed, have the treatments changed in the period of time since this study began?
DR. ROWAN CHLEBOWSKI: Well, of course we evaluate only one dose and schedule.
GWEN IFILL: That’s true.
DR. ROWAN CHLEBOWSKI: And that was the dose and schedule that was being used by 95 percent of U.S. women when the study started.
GWEN IFILL: Which is Prempro, right?
DR. ROWAN CHLEBOWSKI: Which is Prempro. Conjugated equine estrogen and medroxyprogesterone acetate is one pill.
Now the dosage is about half that’s commonly used. Other preparations are being used. But, of course, we don’t have safety information on lower dose or different schedules or different drugs. You would have to do a repeat safety study, which would again take years and years to complete.
GWEN IFILL: Dr. Gralow, how — how — what should people make of this? What should women make of this? What kinds of risks vs. benefits should they be applying to this kind of information?
DR. JULIE GRALOW: I think, if we’re talking estrogen plus progestin, we really no longer can feel that it’s safe to stay on it for a long period of time.
The main reason to use that combination is to help get through those hot flashes, the insomnia, the mood swings that go along with the period that we call perimenopause, as we’re kind of getting into menopause.
I do think serious considerations should be given to other ways of giving progestin. I agree with Dr. Chlebowski that we don’t have big, huge 10,000-, 20,000-patient studies with different forms of progestin.
But in a study without any progestin alone, we didn’t see increased breast cancer. Perhaps progestin can be used just a few times a year to help protect our uterus, or maybe different forms of progestin, such as an IUD giving progesterone, might be another alternative, if you have a uterus.
If you don’t have a uterus, don’t take progestin. That’s a clear answer.
GWEN IFILL: Dr. Chlebowski, I’m curious whether this is just indicated — the negative indications here are only about breast cancer, or about other cancers as well.
DR. ROWAN CHLEBOWSKI: Yes. I think, in the last October, we reported from the WHI in the same study that lung cancer mortality was increased by 71 percent. That was statistically significant. And so these two taken together really are really quite a tandem, when you say that estrogen plus progestin taken for about five years significantly increases the risk of deaths in the two most common causes of cancer death in women.
So that I think raises the bar for women to think how serious their symptoms or limiting their symptoms should be before they should consider starting this therapy.
GWEN IFILL: Is it raising the bar for doctors as well when it comes to prescribing it?
DR. ROWAN CHLEBOWSKI: I think so. I have been looking at the news reports coming out this afternoon. And I think there’s been a number of people who, surprisingly, are saying now that they have more reservations than they did before these last two reports.
GWEN IFILL: Dr. Gralow, do you have more reservations?
DR. JULIE GRALOW: Well, I’m a breast cancer physician. Most of my patients have breast cancer. And I’m not recommending estrogen for them. So, it doesn’t really change my standard practice.
As for what I will be discussing with patients at increased risk for breast cancer, if you really need, for symptoms — and symptoms only — to go on some estrogen, do it at the lowest dose for the shortest amount of time. For osteoporosis, for cholesterol, for other issues, or vaginal, urogenital health, we have other options. And we should be using those first.
GWEN IFILL: Dr. Chlebowski, is there an immediate action that the medical industry or the pharmaceutical industry can take, say, put warning labels on these kinds of drugs?
DR. ROWAN CHLEBOWSKI: Well, I guess the FDA, you know, is responsible for the labeling.
And I, for one, would like to see a little bit more emphasis on the cancer risk on the label. There is a — there is a label warning for breast cancer risk, not for lung cancer risk. Again, that’s a Federal Drug Administration decision as to what the labeling should be.
GWEN IFILL: Is that something which is at all useful, Dr. Gralow?
DR. JULIE GRALOW: Well, I think that, you know, it’s helpful. It will make physicians and make patients think a little bit harder about it. It really doesn’t help you make the decision.
GWEN IFILL: And that’s a decision that still has to be up to the woman, rather than just the doctors or the FDA, I gather?
Dr. Julie Gralow…
DR. JULIE GRALOW: Well, it’s a complicated…
GWEN IFILL: Oh, go ahead.
DR. JULIE GRALOW: It’s a complicated discussion…
GWEN IFILL: Yes.
DR. JULIE GRALOW: … you know, between the patient and the physician. And there are risks and there are benefits. And it’s a very individualized decision.
GWEN IFILL: It’s finding that balance. Dr. Julie Gralow and Dr. Rowan Chlebowski, thank you both very much.
DR. ROWAN CHLEBOWSKI: You’re welcome.
DR. JULIE GRALOW: Thanks.