Dr Grabelsky: This 72-year-old woman became postmenopausal at age 35 as a result of a breast carcinoma. I don't have all the details because it was in 1962. She apparently had node-positive disease and underwent a radical mastectomy, chest wall radiation and ovarian radiation at that time, and she did well for 37 years.

In 1999, she presented with a minimal cough, which persisted despite a trial of antibiotics, et cetera, and was noted to have some small pulmonary nodules on chest X-ray, which were confirmed on CT scan. She underwent a broncho-scopy, at which time a small endobronchial lesion was noted and biopsied and revealed a moderately differentiated adenocarcinoma, which was strongly estrogen receptor-positive.

Dr Love: At that point, she was 72 years old and had undergone adjuvant ovarian radiation 37 years ago.

From the floor: What about her other breast?

Dr Grabelsky: She had mammography and MRI scanning of the breast, as well as a physical examination, and there was nothing abnormal.

Dr Love: How symptomatic was she at that point?

Dr Grabelsky: Minimally symptomatic, just a nonproductive cough. No shortness of breath. Excellent performance status.

Dr Love: And no other evidence of disease?

Dr Grabelsky: Complete staging workup, including PET scan, was negative.

Dr Love: Can you describe the pulmonary disease?

Dr Grabelsky: There were about eight to 10 nodules, bilaterally, mostly in the upper lobes, which were one to two centimeters. Also, her tumor markers, both CA 15-2 and CA 27-29, were elevated.

Dr Love: Lisa, what do you think you would do in this kind of situation?

Dr Carey: She's 72 years old and is asymptomatic with this odd picture of endobronchial lesions. I would use an aromatase inhibitor. You don't want to make her sick, and she's asymptomatic with disease only in her lungs.

Dr Love: What did you do, Dr Grabelsky?

Dr Grabelsky: We gave her letrozole, and she had a very good response. The nodules shrank; they did not completely disappear but they were a subcentimeter. Her tumor markers completely corrected, and she did well for over a year until December of 2002.

Dr Love: What happened at that point?

Dr Grabelsky: At that time, her markers started going up and restaging evaluation revealed that the nodules were enlarging again. No new nodules were identified and no metastatic disease anywhere else.

Dr Love: So, she's back kind of where she started from?

Dr Grabelsky: Again, minimally symptomatic, just a cough.

Dr Love: Genny?

Dr Grana: I have two issues to discuss. I haven't been in practice 35 years, so I can't say I've seen a relapse this far out. It is possible that this is a relapse of her first cancer. I guess it's also possible that this is a metastases from another cancer that you haven't found in the opposite breast. This is clearly a patient for whom genetic testing would have implications for her family, not for her at age 72.

At this point I would probably go back to tamoxifen and, again, it's that data from the anastrozole versus tamoxifen trial that tells us that, if you use an aromatase inhibitor first and you go to tamoxifen, about 60 percent of patients derive a clinical benefit. It was a retrospective look, not a builtin crossover, but I like tamoxifen.

Dr Love: Bob, what do you think you would do in this situation, progressing on an aromatase inhibitor?

Dr Carlson: I think the idea of tamoxifen is a great one, and that's probably what I would do.

The one thing you've told me that's very surprising is that she only had a two-year duration of response to an aromatase inhibitor. I would have expected a three-, four- or five-year duration of response.

Dr Love: What happened with this patient?

Dr Grabelsky: We had a discussion and at that point she actually was on several other medications, and we discussed tamoxifen versus fulvestrant, which had just become available. Because of financial issues about paying for medications, she elected to use fulvestrant. She had an excellent response. Nodules have decreased, tumor markers have again normalized, and she's stable after nine months on fulvestrant. My concern is that, if she's staying on fulvestrant, do we know what are the long-term toxicities of this agent?

My other question was: If she stops responding to fulvestrant, could you go back to something like tamoxifen?

Dr Carlson: We know that responses do occur to endocrine therapy after fulvestrant (Figures 5.1, 5.2). I don't think we have really long-term data in terms of multiple years of fulvestrant treatment with follow-up. Certainly, the toxicity experience to date suggests that the toxicities are not cumulative with fulvestrant, and the toxicity experience at month 12 is similar to the toxicity experience at month four or six. Only a handful of patients have been on fulvestrant for longer than 18 months or so.

Dr Love: Is she receiving the two 2.5-cc injections?

Dr Grabelsky: Yes, the two injections. She has had an occasional irritation in her buttock, but other than that, she's tolerating it extremely well and she's very active, traveling to visit her children and grandchildren. Her performance status is zero.

Dr Love: Is she thin, or not so thin?

Dr Grabelsky: Relatively thin. She is also on alendronate sodium (Fosamax® ), so she comes in monthly for that and the fulvestrant (Faslodex®). She had some osteo-penia, which developed in the interim when she was on the aromatase inhibitor.

She does not have true osteoporosis, but has had some diminution in her bone density so she was started on alendronate sodium at that time.

Figure 5.1

Figure 5.2

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