Larry Norton: From A to B in Breast Cancer
Dr. Miller: We have 2 studies looking at various aspects of adjuvant therapy that also have theoretical and practical implications. First is the aTTom trial, the second large trial looking at 5 vs 10 years of tamoxifen, with very similar results to the ATLAS trial.
This poses a particular challenge, especially for patients who started tamoxifen during premenopause, became amenorrheic, and are now at 5 years. Do you continue the tamoxifen? Do you switch them to an aromatase inhibitor? Does it matter?
Dr. Norton: I am going to tell you my view. It looks like 10 years of hormonal therapy is advantageous. That 10 years might be composed partially of a selective estrogen receptor modulator (SERM) like tamoxifen and partially of an aromatase inhibitor. We don't know. It's possible that even longer is going to be better. That is a question that we have to ask. One questions that has come up frequently, and even during the first presentation is, "Dr. Norton, I finished my 5 years of tamoxifen 6 years ago. Should I take another 5 years?" We should say pretty clearly that there is no evidence to support that, and you should not return to it.
Dr. Miller: Suppose I finished my tamoxifen 2 years ago.
Dr. Norton: There are no answers to these questions. Probably within a year it would make some sense [to continue tamoxifen] because of the half-life of the drug and the prolonged biological effect. There could be additional benefit, because in patients who don't even have breast cancer, drugs like tamoxifen can reduce the incidence of breast cancer. One thing that we have seen in these trials is prevention of contralateral disease as well as an inhibition of the metastatic process. It fascinates me that in the 10-year tamoxifen data, we are entering a very interesting sociologic period. It used to be clear that if you have an infection, you take an antibiotic, the infection goes away, and you're done. Most modern therapies, especially for cancer, are yin and yang: You are going to get this; you are going to lose this. You are going to have a lower incidence of recurrence of breast cancer, and now there is evidence supporting a lower death rate from breast cancer, but you may have to deal with endometrial cancer. So, that is not a clear answer.
I would balance a nonlethal endometrial cancer against a lethal breast cancer any day, and that is something that we all have to keep in mind as we proceed. Nevertheless, people are generally reluctant to take medicines they know can actually give them cancer. That is something that we are going to have to deal with.
Considering the average age of onset of breast cancer, we won't run into this problem too often, because we will be able to use the aromatase inhibitors in patients who are in menopause, and most of our patients are in or close to menopause. It's not going to be a huge percentage of the population who must be treated and who will have to deal with this issue now. It was a well-done, carefully analyzed study. We are talking about 10 years of tamoxifen for women who fit the criteria of being premenopausal and requiring adjuvant hormonal therapy, with full awareness of the risks of carcinogenesis to the endometrium and the need for monitoring. With aromatase inhibitors, it is much easier.
Dr. Miller: For prolonged duration, tamoxifen is a viable option for postmenopausal women who struggle with toxicities with aromatase inhibitors. There certainly is a subset of women who find the toxicities intolerable.
Dr. Norton: It is a relatively small subset if you switch around between the available drugs. Usually you can find a drug that is tolerable in most cases, but a certain percentage of patients have problems. Going back to a SERM such as tamoxifen is a very reasonable thing to do. We all do it.
The Yin and Yang of Adjuvant Treatment
Dr. Miller: We have 2 studies looking at various aspects of adjuvant therapy that also have theoretical and practical implications. First is the aTTom trial, the second large trial looking at 5 vs 10 years of tamoxifen, with very similar results to the ATLAS trial.
This poses a particular challenge, especially for patients who started tamoxifen during premenopause, became amenorrheic, and are now at 5 years. Do you continue the tamoxifen? Do you switch them to an aromatase inhibitor? Does it matter?
Dr. Norton: I am going to tell you my view. It looks like 10 years of hormonal therapy is advantageous. That 10 years might be composed partially of a selective estrogen receptor modulator (SERM) like tamoxifen and partially of an aromatase inhibitor. We don't know. It's possible that even longer is going to be better. That is a question that we have to ask. One questions that has come up frequently, and even during the first presentation is, "Dr. Norton, I finished my 5 years of tamoxifen 6 years ago. Should I take another 5 years?" We should say pretty clearly that there is no evidence to support that, and you should not return to it.
Dr. Miller: Suppose I finished my tamoxifen 2 years ago.
Dr. Norton: There are no answers to these questions. Probably within a year it would make some sense [to continue tamoxifen] because of the half-life of the drug and the prolonged biological effect. There could be additional benefit, because in patients who don't even have breast cancer, drugs like tamoxifen can reduce the incidence of breast cancer. One thing that we have seen in these trials is prevention of contralateral disease as well as an inhibition of the metastatic process. It fascinates me that in the 10-year tamoxifen data, we are entering a very interesting sociologic period. It used to be clear that if you have an infection, you take an antibiotic, the infection goes away, and you're done. Most modern therapies, especially for cancer, are yin and yang: You are going to get this; you are going to lose this. You are going to have a lower incidence of recurrence of breast cancer, and now there is evidence supporting a lower death rate from breast cancer, but you may have to deal with endometrial cancer. So, that is not a clear answer.
I would balance a nonlethal endometrial cancer against a lethal breast cancer any day, and that is something that we all have to keep in mind as we proceed. Nevertheless, people are generally reluctant to take medicines they know can actually give them cancer. That is something that we are going to have to deal with.
Considering the average age of onset of breast cancer, we won't run into this problem too often, because we will be able to use the aromatase inhibitors in patients who are in menopause, and most of our patients are in or close to menopause. It's not going to be a huge percentage of the population who must be treated and who will have to deal with this issue now. It was a well-done, carefully analyzed study. We are talking about 10 years of tamoxifen for women who fit the criteria of being premenopausal and requiring adjuvant hormonal therapy, with full awareness of the risks of carcinogenesis to the endometrium and the need for monitoring. With aromatase inhibitors, it is much easier.
Dr. Miller: For prolonged duration, tamoxifen is a viable option for postmenopausal women who struggle with toxicities with aromatase inhibitors. There certainly is a subset of women who find the toxicities intolerable.
Dr. Norton: It is a relatively small subset if you switch around between the available drugs. Usually you can find a drug that is tolerable in most cases, but a certain percentage of patients have problems. Going back to a SERM such as tamoxifen is a very reasonable thing to do. We all do it.