Edited excerpt from the discussion:

DR BLAUSTEIN: This is a 73-year-old woman who I have been following for approximately three years. She had a lumpectomy with a 1.4-centimeter, moderately well-differentiated tumor. There were two focally positive lymph nodes and her tumor was strikingly ER/PR-positive and HER2-negative. She had no family history of breast cancer.

She had mild hypertension and had been on hormone replacement therapy for approximately eight to 10 years, but stopped on her own about six or seven years before I saw her.

She was a retiree and had worked with her husband in the clothing industry and was fairly active. This was the family’s first experience with any cancer, let alone breast cancer.

DR LOVE: Kathy, how would you have thought through the numbers in this situation?

DR MILLER: Can you tell me more about what focally positive lymph nodes mean? I’m trying to get a sense of whether I should think about this woman as someone who really has significant lymph node disease and is at much greater risk, or if this is micrometastatic disease.

DR BLAUSTEIN: It was more than micrometastatic disease, but there was not diffuse effacement of the lymph glands. It was somewhere in between.

DR MILLER: Two positive nodes with this small tumor and other very good histologic features actually have less of an impact on her risk of recurrence than you would expect if you had the same features in a poorly differentiated, ER-negative tumor.

She probably has approximately a 10 to 15 percent risk of dying from this breast cancer over the next 10 years, if you do nothing, since she is otherwise quite healthy and doesn’t have other health issues. She clearly needs hormonal therapy. Her benefit from chemotherapy will be quite low. It’s probably only in the range of three to four percent in absolute terms if you gave her fairly aggressive chemotherapy.

I have a lot of 73-year-old patients who think that is absolutely worthwhile. She is healthy, and there is nothing that I heard in her history that would particularly concern me about her risk of serious toxicity with chemotherapy. I would need her to help me a little bit.

One of our challenges over the next several years, as we obtain more details about biologic assays like the Genomic Health assay, is how to integrate that information with tumor size and lymph node status, which are still clearly important.

Right now, we don’t know which of these pieces of information should really be the driving factors in our decision-making. I certainly would not advocate sending an Oncotype DX assay in folks who have nodepositive disease, because we don’t know how to integrate that information, but I am a little bit perplexed by a small primary tumor that is strongly ER-positive and not poorly differentiated and has found its way into two lymph nodes. There is a disconnect between the tumor size and the biology in that she has regional metastases.

DR LOVE: It seems that you are open to the idea of chemotherapy and might put the decision in the patient’s hands. Would you still feel the same way if she were 83 years old?

DR MILLER: If she’s 83 and quite healthy, I probably would still have a very similar discussion with her. If she asked, “What’s your best recommendation?” my recommendation would be not to have chemotherapy. The reality is a healthy, very functional, independent 83-year-old woman can expect to live to age 90.

DR LOVE: How about in an 88-year-old?

DR MILLER: I would not use chemotherapy.

DR LOVE: Nancy, how would you have thought through chemotherapy in this patient?

DR DAVIDSON: I’m a little less enthused about chemotherapy for her, which is not surprising, because I’m a big hormone enthusiast. I am pretty enthused about the update in San Antonio that Kathy Albain presented on her trial of tamoxifen versus CAF with tamoxifen versus CAF followed by tamoxifen (Albain 2004). This was a retrospective subset analysis suggesting that postmenopausal women who had the small tumors, one to three involved lymph nodes and ER-positive, HER2-negative disease, experienced no benefit from CAF chemotherapy.

DR LOVE: What about selection of hormonal therapy in this patient, Kathy?

DR MILLER: Three years ago, most of us would have talked to her about tamoxifen unless she had a clot risk or other comorbidities. Today, most folks would talk to her about an aromatase inhibitor as the preferred choice, although I think she needs to hear about tamoxifen also. I think they’re both still reasonable choices.

If she is of slight build and already had substantial osteoporosis, I certainly wouldn’t feel bad about putting her on tamoxifen to try and avoid complicating those other health issues, but I suspect most folks would treat her with an aromatase inhibitor up front, and I think that is a perfectly reasonable option.

DR LOVE: Which aromatase inhibitor?

DR MILLER: I try to stick close to the data because I don’t want to give myself credit for knowing things that may be wrong.

We now have up-front data with anastrozole (Howell 2005) or with letrozole (Thurlimann 2005) — but with data that we have in hand to date (4.1), I probably would give her anastrozole just because we’ve had that upfront data longer and that’s what I’m used to doing.

DR LOVE: Dr Blaustein, can you update us on this woman’s current situation?

DR BLAUSTEIN: I did not strongly encourage chemotherapy, and she and her family weren’t very eager for her to start chemotherapy, so she started tamoxifen and has been clinically NED.

When the data started accumulating about switching people from tamoxifen to aromatase inhibitors (Boccardo 2003; Coombes 2004; Jakesz 2004), I discussed that option with her.

She is of average body build and is followed by a good internist who has monitored her bone density. She takes calcium and vitamin D.

After discussing this option with her and making sure she understood the data were trending toward black and white, but not there yet, I switched her to exemestane.

DR LOVE: Kathy, how do you approach patients who are postmenopausal and have been on tamoxifen for a couple of years? Do you bring up the possibility of switching to an AI in all these patients?

DR MILLER: I do bring this up to all of these patients. We still have fairly limited data, but the IES trial was a large trial and very well done. The results look fairly clear that switching decreases the risk of recurrence as well as the risk of contralateral disease. At this point, there is no difference in overall survival.

DR LOVE: Kathy, we now have a new data set that just came out a couple of months ago, looking at switching to anastrozole. That German/Austrian study (Jakesz 2004) was very similar in size to the IES study and, actually, the results were similar also. What are your thoughts about those data, and how did that impact the way you take care of patients?

DR MILLER: My first thought was, “It’s nice when the data confirm what we think we already know and gives us all that warm, fuzzy sense that we’re on the right track and are making improvements for our patients.” It also certainly confirms that a postmenopausal woman with ER-positive disease probably ought to be exposed to an aromatase inhibitor at some point in her therapy, though we still don’t know what the optimal sequence might be.

I can’t tell you that the German/Austrian data really changed my practice. I was in the habit of talking to women about switching in midstream to exemestane. The trials are similar size. We have a “skosh” more follow-up in the exemestane trial (Coombes 2004), for whatever that’s worth.

Exemestane and anastrozole are both equally reasonable, but I must say, I’m a creature of habit. Once I have a habit fairly well established, having merely another choice, unless it is meaningfully better, less toxic or less expensive is not usually enough to get me to change what I’m doing.

If this is a woman who says, “I’m really having no toxicity on tamoxifen. I’m feeling well. It’s cheap, and I’m happy staying with what I know is working for me,” I would not feel compelled to push her to switch. There is some incremental benefit there and, at this point, we don’t know how to select those women who really preferentially benefit from an AI.

I talk to all of these women, and probably 70 to 80 percent of them find switching quite reasonable. We also switch with the clear understanding that if the patient finds the toxicity substantially difficult and more troublesome, we’re not obligated to stick with that switch. We can switch back if the new therapy is not working for the patient on the toxicity front.

DR LOVE: Nancy, there were hopes that exemestane, which is a steroidal aromatase inhibitor, might be bone sparing. My read on the IES switching data (Coombes 2004) is that really hasn’t panned out. Is that your take?

DR DAVIDSON: That’s my take. It’ll be interesting to see other data as they emerge, but it looks to me like all of the AIs appear to be nonbone sparing.

DR LOVE: Nancy, what about the timing of the switch during five years of therapy? We have data at two to three years, but we don’t have data at one year. We don’t have data at three and a half and four years.

Our group recently hosted a panel discussion during which Gabe Hortobagyi simplified the issue by saying, “If I see a postmenopausal woman who’s on adjuvant tamoxifen, I just switch her to an aromatase inhibitor.”

Do you wait until patients get to the two year point or the five-year point?

DR DAVIDSON: I find that what used to be a very short follow-up visit is now a long visit, because every time we end up talking about, “Is this the time we’re going to make the switch or not?” I think that we’ve generally decided that most of these women are going to get an AI, but we’re sort of betwixt and between a lot of times.

Sometimes they come in and say, “Yeah, I heard about this, but I’m fine. You said five years of tamoxifen, and I don’t want to change anything right now.”

So then we revisit it again the next visit. I don’t know the answer except that, particularly for the node-positive patients, I’m sure they’re going to receive an AI. It’s just a question of when we want to pull the trigger.

DR HART: An Austrian study showed that you can almost totally abrogate bone loss with IV zoledronic acid given every six months (Gnant 2004; [4.2]). Is there anyone who’s doing that routinely now? If it were reimbursed, would you do that routinely in these patients?

DR LOVE: Nancy, that was actually done in a trial of premenopausal women who were receiving an LHRH agonist plus either tamoxifen or anastrozole. Those data have been presented twice, most recently at the 2004 San Antonio meeting (4.3), and as Lowell said, it looks like the bisphosphonate completely abrogated the bone loss. What were your thoughts about that?

DR DAVIDSON: Looks like a great result, but I don’t think it’s translated yet into clinical practice. We’re using whatever oral bisphosphonate we like to use in that setting, but I’m very curious about that. For osteoporosis, you can give the bisphosphonate just once or twice a year. It’s pretty impressive.

I think we should stay tuned for the NSABP clodronate trial. That has closed to accrual, and we’re waiting for follow-up. That may answer a lot of questions for us and speak to all of these issues.

Select publications