Estrogens in Ovarian Cancer & Breast Cancer Survivors

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Hans van der Slikke, MD: “It’s September of 2001, and we’re in Paris at the 2nd Controversies Conference in Gynecology and Obstetrics. Next to me is Professor Leon Speroff, and he just chaired the session about the controversies in hormones and gynecological cancer. Welcome, Professor Speroff, I want to discuss with you two topics that you had in your session. The first one is about the controversy there is between the relationship between hormones and ovarian cancer.”

Leon Speroff, MD: “This subject received attention this past year with a publication from the American Cancer Society that indicated that there was an increased risk of ovarian cancer with long term use of hormone therapy. This is added to by a presentation here at this meeting from a Danish study that found that there was an increased risk associated with an accumulative dose of estrogen over time. However, there are many studies that have not found an increased risk. The difficulty is that the risk of ovarian cancer is influenced by many factors, for example, parity, breast-feeding, oral contraceptives, body size – it is a long list. Studying ovarian cancer by necessity because of its frequency or prevalence requires case control and cohort study designs. The accuracy of a case control and a cohort study is very much influenced by how identical the case group is to the control group. Because ovarian cancer is influenced by so many factors, it’s very difficult to have identical case and control groups and the reason is that hormone users are different. Women who choose to use post-menopausal hormone therapy by and large have different lifestyles, different body sizes, they have different pregnancy histories, and their use of oral contraceptives is different. All of these things affect the risk of breast cancer so even though epidemiologists adjust for these factors with mathematics one cannot be confident that the conclusion is real.”

Hans van der Slikke, MD: “Could one say that even for breast cancer one has the same problem and this is a less frequent disease?”

Leon Speroff, MD: “It’s the very same problem that exists with the studies of breast cancer, it is less. In my view, it is an important factor but it is even more important with ovarian cancer because the disease is less prevalent, the number of cases in the studies is smaller and, therefore, even more subject to this difference. So in my own practice, I emphasize to patients that there are more studies that have not found an increased risk of ovarian cancer and that the new studies have found a slightly increased risk. They are outnumbered by the negative studies, and I’d rather present that kind of balanced point of view.”

Hans van der Slikke, MD: “Is this about the same as you do in breast cancer?”

Leon Speroff, MD: “The whole subject with breast cancer that we discussed in this conference was hormonal treatment for breast cancer survivors. As we are more and more successful in detecting breast cancer early and treating it better, more and more women face this very difficult decision. We won’t know the right answer until we have the results of randomized trials, which are underway in Scandinavia, the United Kingdom, and the United States but it will be ten years before we see data. Until then, what we have in the literature is about 10 or 12 reports totaling over 1,000 patients all of which have found no increased rate of recurrent disease in hormone users so that’s very reassuring. Now the problem is that those studies are not randomized trials, and they use hormones on probably low risk women. Clinicians choose to provide hormones to women they regard as low so one would expect a low rate of recurrent disease. At the same time, you can look at that literature of over 1,000 patients and say at least it’s reassuring that there was no evidence of an increased rate of recurrent disease in the hormone users. By the way, that was true whether the receptors were positive or negative for estrogen. My own position is that the patient is right; until we have data from randomized trials, whatever the patient wants should be supported because there is no right or wrong answer. So if a patient wants to take an unknown risk and wants the benefits associated with hormone therapy, I support that. If the patient is terrified of estrogen therapy because her oncologist has convinced her it would be a bad thing to do, I support that. Until we have randomized clinical trial data, I think it’s appropriate for the clinician to support whatever the patient wants.”

Hans van der Slikke, MD: “Do you think we’ll have to wait another ten years to have the answer?”

Leon Speroff, MD: “Another case control study or another cohort study will not clarify the situation. We won’t know the right answer until we have the randomized clinical trial data, that means it’s going to be a difficult decision for at least another ten years.”

Hans van der Slikke, MD: “So it will stay a controversy and we can tell this story at the next conference.”

Leon Speroff, MD: “We can revisit it every year.”

Hans van der Slikke, MD: “Thank you very much for this interview, Dr. Speroff.”

Leon Speroff, MD: “My pleasure.”