Dr Joshua: This is a 73-year-old woman whom I saw after she had a mastectomy for a 6.5-centimeter, ER/PR-positive, HER-2 negative, infiltrating, poorly differentiated ductal carcinoma. Three out of 12 axillary nodes were positive. The lesion had been detected on a screening mammogram. She was started on AC chemotherapy, which will be followed by docetaxel, chest wall radiation therapy and anastrozole.

Dr Love: Can you talk a little bit about this woman - how active she was and what her general condition was like?

Dr Joshua: She's a retired nurse. She is an otherwise healthy woman. I was a bit surprised that she had such a large tumor, and that it was only discovered on a mammogram. I only saw her after the surgery, and she absolutely denied having any palpable lumps. She's very active and intelligent and able to understand what's going on with her disease.

Dr Love: It's interesting that she was a nurse. What was her attitude towards the possibility of receiving chemotherapy? How concerned was she about toxicity or was she completely focused on the tumor?

Dr Joshua: She was not concerned

about the alopecia. After explaining to her about the nausea, vomiting and the preventive medication we have today, she was not concerned about that either. She's on preventive growth factor and she's tolerated the treatment fairly well so far on AC.

Dr Love: And what was it that went into your decision to use AC, docetaxel and anastrozole?

Dr Joshua: She has a large tumor, positive lymph nodes and, in my opinion, she clearly would benefit from adjuvant chemotherapy. In terms of what drugs to choose, I thought about epirubicin instead of doxorubicin, but I'm much more used to using doxorubicin, and that's the first thing that came to mind. In terms of following that with docetaxel versus paclitaxel, I prefer docetaxel -especially in elderly women -because I think it's probably a better drug.

Dr Love: What about the decision of anastrozole versus tamoxifen? Did you present both options? And how did that discussion go?

Dr Joshua: I prefer anastrozole because of the ATAC trial, particularly because this woman is at a high risk of developing metastatic disease. I would certainly use an AI, and I would choose anastrozole.

I usually tell patients that anastrozole has fewer side effects, but if the patient has already had a hysterectomy, that is not such a major issue. We talk about bone density. We talk about uterine cancer.

I've used tamoxifen for many years and I only had one patient who was diagnosed with endometrial cancer, and she had a hysterectomy and did fine. So, I usually tell patients that even if they do develop endometrial cancer, the chance of dying from this is close to zero if the patient is followed carefully. In someone like this woman, with a large tumor and positive nodes, I prefer to use anastrozole.

Dr Love: So, in reviewing your practice, are you more likely to use

anastrozole in a higher-risk situation, like this node-positive patient (Figures 3.1, 3.2)?

Dr Joshua: Yes.

From the floor: What about the issue of using taxanes in postmenopausal women with ER-positive tumors?

Dr Carlson: That issue and this entire case are complex, and it shows us how much we don't know. The patient is apparently in otherwise good health, but because she's over 70, the confidence we have that chemotherapy is of benefit is very low. For those of you who are historians, if you go back to the initial overview analysis of polychemotherapy, the only negative number in that entire paper was an increased death rate in women over 70 given chemotherapy. It was the only negative number in the entire publication.

Figure 3.1

Figure 3.2

In the second and third overviews, they said they didn't have enough patients to comment. In the most recent, unpublished overview, there's a very small - a couple percent -risk reduction in chemotherapy in women over the age of 70, but it's not statistically significant. So, I have a lot of reservations about whether chemotherapy should be used or not. The patient's preference and how aggressive she wants to be is very important.

Because of the combination of concerns about toxicity, the hormone receptor positivity and so on, I personally would not add a taxane to this woman's therapy. If I used a taxane, I actually would prefer paclitaxel because I think that docetaxel is a difficult drug, especially in terms of myelosuppression, and especially in older women.

I think that older women have a much more difficult time with the prolonged courses of steroids that are required with the paclitaxel administration. (Figure 3.3).

From the floor: I have a comment regarding age. It's always very controversial. One of the problems is that relatively few older women are enrolled in clinical trials. And then there's Hy Muss cheering the country on, saying, "Look, we are undertreating elderly women. We're already biased as physicians, not even presenting the option of chemotherapy because in our minds we're already against it and have decided not to offer it to them."

I think if we increase the number of elderly patients accrued into clinical trial, we would eventually have the data in elderly people. And what these elderly clinical trials should really be looking at is, in addition to disease-free and overall survival endpoints, we must consider comorbidities.

In our practice, for women who are 65 and older, we give them the option. If they're very healthy 65-year-olds -and we do have a lot of them here in southern Florida - we offer chemotherapy. I think it's their prerogative to know that the benefits may be small and modest, but real. Just like we do with small increments as in adjuvant therapy altogether (Figure 3.4).

Figure 3.3

Dr Love: What about the issue of hormone therapy in postmenopausal women in clinical practice?

From the floor: We're using a lot more anastrozole. Now, there are women who read a lot and come with their thick Internet files, and they will demand either anastrozole or tamoxifen.

But we tend to use anastrozole unless they are already at increased risk for fracture because of osteoporosis. At that point, we back off on aromatase inhibitors.

Dr Carlson: Every time we come up with new clinical trial data set with the magnitude of the ATAC trial, it creates a crisis. There tends to be a chaos theory prevailing as we sort of respond to the new information and assimilate it.

I think what you're seeing right now is that there is this sort of mini-crisis as we try to understand whether anastrozole truly - when all is said and done - is going to be superior, not only in terms of disease-free survival, but also overall survival. And we're going to have problems interpreting data in the transition.

Dr Love: When you look at the choice between tamoxifen and anastrozole, how much of a factor is it if the woman has a prior hysterectomy?

Figure 3.4

Dr Schwartz: I'm not really concerned about the uterine cancer. It really doesn't influence me. I am more concerned about cardiovascular risk factors that would cause me to stay away from tamoxifen. Generally, I'm using more and more aromatase inhibitors.

Dr Grana: I'm much more concerned about the thrombotic risk in the older woman. If I have a woman who's in her seventies or eighties, a CVA is a life-debilitating event. So, I weigh in thrombotic risk much more than I ever weigh in uterine cancer.

From the floor: Women make that choice and take that risk every day when they take hormone replacement therapy or oral contraceptives and they don't even think about it. But tamoxifen is such a studied drug, and it's so controversial that you have to present everything.

From the floor: Basically, I look at the entire patient. I personally like tamoxifen, but I discuss the literature about aromatase inhibitors with every patient. At the same time, a lot of these patients have limited funds.

It's very important that they take their medication, so their ability to pay or be reimbursed for the medication is a very important aspect. For some patients, aromatase inhibitors are prohibitively expensive.

Dr Grana: Just to bring up a related point, most of us would choose AC followed by paclitaxel for the same extra benefit that we see with anastrozole over tamoxifen. Adding paclitaxel to AC probably adds at least $10,000 to the cost and yet we accept it because the patient doesn't have to pay for it.

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