• Five-centimeter mass in the upper outer quadrant of the left breast
• ER-positive, PR-positive, node-positive (7/10)
• Invasive lobular carcinoma
• Underwent modified radical mastectomy (1-mm margin)
• Myocardial infarction more than 10 years ago

Key discussion points:
	Adjuvant chemotherapy for elderly patients
	Incorporation of ADJUVANT! into clinical practice
	Selection of adjuvant hormonal therapy in patients with comorbidities
	Quality control with ER testing

DR ABEL: This patient became aware of a palpable left breast abnormality in August 2003. Mammography demonstrated a mass in the upper outer quadrant. A core biopsy in late August identified an invasive lobular carcinoma. A left modified radical mastectomy in early October confirmed invasive lobular carcinoma, pleomorphic type, at least five centimeters at its greatest dimension. There was no vascular or perineural invasion, and the tumor extended to within one millimeter of an inked margin. The tumor is metastatic in seven of 10 axillary lymph nodes and is strongly positive for estrogen receptor and intermediately positive for progesterone receptors.

This woman is 79 years old and lives with her husband. Her performance status would probably be one, but her lifestyle would be characterized as limited because she was physically frail. Overall she was alert, conversant and pleasant.

In 1992 she sustained a myocardial infarction, and she is also symptomatic with a peripheral neuropathy.

DR LOVE: We've been talking about the different perspectives that patients and doctors have on adjuvant therapy. Some patients want everything possible, and others are more conservative. Where does this woman fit in?

DR ABEL: We consulted ADJUVANT! and I showed her the graphic representation of the results. It became very clear that chemotherapy was not worth pursuing. She had comorbidities in terms of peripheral neuropathy and ischemic cardiac disease, so the administration of chemotherapy would have been problematic.

DR FOX: I think most of us try to begin with a big-picture view of a woman's options. In our practice, we use Dr Ravdin's program fairly often. I don't know that I would use it for this case because the issues become somewhat self-evident due to the comorbidities.

I always return to the Oxford overview, as it continues to remind us that the worth of chemotherapy in reducing the risk of dying from breast cancer always seems to be diminished in the older patient relative to the younger one.

In cases like this, I think most of us quickly develop a bias. We'd rather not give this woman chemotherapy for a whole lot of reasons, but even in a healthy 79-year-old the benefit is going to be somewhat attenuated relative to someone who is 39.

In this frail, nearly 80-year-old woman with comorbidities, I can't envision the worth of any chemotherapy regimen. You've given very good reasons not to give this woman a taxane-based therapy. You've given fairly good reasons to be concerned about anthracycline-based therapy.

That leaves us with CMF. If you look hard at the contribution of CMF to the outcome in older patients, it's rather meager in the context of estrogen receptor-positive disease when you have tamoxifen, aromatase inhibitors or both. I would not give chemotherapy to this woman.

DR LOVE: If this woman was extremely healthy without any comorbid illnesses, would that change your approach?

DR ELLEDGE: I don't think it would change much. When I explain to patients the decision between hormonal therapy or combination hormonal/chemotherapy, I make it very clear that hormonal therapy is more important, so that they don't agonize too much over this decision.

Many patients feel that chemotherapy is more important, but in receptor-positive disease you generally get twice the benefit from hormonal therapy. I think the bottom line is that I would still recommend hormonal therapy alone.

The choice of hormonal therapy is tougher because there are pros and cons to both tamoxifen and aromatase inhibitors. With tamoxifen, clotting events are age-related, so I would say that a person like this has a clotting event risk over a five-year period of about two to three percent, which is pretty high. On the other hand, aromatase inhibitors have osteoporotic risk.

DR LOVE: One of the things I've always liked about the Ravdin model is that it takes age and comorbid illness into consideration and as you start looking at the numbers, the benefit of therapy is diluted out. What numbers did you derive in this case, and what happened with your discussion concerning choice of therapy?

DR ABEL: With no additional therapy, only one out of 100 women would be alive and without cancer at 10 years; 37 out of 100 would relapse, and 62 out of 100 would die of other causes. That's compelling. With hormonal therapy, you salvage two patients out of 100, whereas with chemotherapy, you salvage less than one out of 100. I showed the patient these numbers and the decision fell into place immediately. The conclusion was obvious that the only way to intervene here was with hormonal therapy. The website indicated a marginal benefit for anastrozole versus tamoxifen, so she started anastrozole as systemic treatment and has tolerated it uneventfully.

DR LOVE: What has been your experience using adjuvant chemotherapy and hormonal therapy in elderly patients?

DR WEISS: In a very healthy elderly person I would consider it, and the debate is not for a 10-year benefit as much as for a five-year benefit. In the person who has other comorbidities and a lower probability of five-year survival, the sacrifice of a half year, even if she were to make it through well, becomes more problematic.

We see an increase in strokes and in the risk of thrombotic events with tamoxifen, and I am beginning to question whether tamoxifen should be used in this population. When we use aromatase inhibitors, we can treat osteoporosis. Unless I see someone with severe, unresponsive osteoporosis, my inclination in the older patient is to treat with an aromatase inhibitor.

DR FAVIS: I agree with the consensus and would not have encouraged chemotherapy. However, in the rare patient who demands it or might derive some benefit from it, I have occasionally used capecitabine. If you are careful with it, I think you have a lot less trouble than with CMF, AC or practically anything else.

DR LOVE: A trial is comparing capecitabine to AC and CMF in elderly people. Richard, what are you doing about the patient with an ER-negative tumor who is 75, 80 or 85 years old?

DR ELLEDGE: Certainly chemotherapy is not as well-tolerated. There is no real cut point, but I give chemotherapy to a few patients who are in their seventies and I see a lot more problems in this age group. I frequently use AC, and even with that I see more problems.

DR LOVE: What can we expect the incidence of ER-positivity to be in a 79-year-old woman using Craig Allred's definition of any cells being positive?

DR ELLEDGE: If we discard the lobular histology, it's more than 80 percent. Lobular histology will drive it up higher, approaching 90 percent. In Europe and the United States, when you do tight quality control at central labs, approximately 20 percent of tumors that are classified as ER-negative will come back positive, so I always retest all ER-negative tumors.

My only other comment is that I agree with your choice of anastrozole. Sometimes we waffle around in these discussions and don't actually say what we would do.

DR LOVE: Richard, you say that sometimes people waffle about choice of hormonal therapy. Are you more inclined toward anastrozole in a HER2-positive patient?

DR ELLEDGE: We have two sets of data that are criticized for being small sets, but they are actually quite consistent and are independent. They show that if you have overexpression of the HER family of receptors, for whatever reason, the aromatase inhibitors are more effective than tamoxifen.

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