Managing patients with osteoporosis on bisphosphonates

My most significant concern is with patients in their early 50s with ER/PRpositive tumors with five or six positive lymph nodes and osteoporosis despite being on alendronate.

The choices are easy in terms of chemotherapy, because these are women whom I will encourage a six-month chemotherapy regimen — AC/paclitaxel or AC/docetaxel. The biggest dilemma in that woman is the choice of tamoxifen or anastrozole, knowing that she’s already osteoporotic and has already received a bisphosphonate. It really has to be shared decision-making in deciding which hormonal agent to use. My philosophy has been — from the first presentation of the ATAC data — to present the risks and benefits, discuss the patient’s concerns and then make a decision.

Other aromatase inhibitors in the adjuvant and metastatic settings

In the adjuvant setting, I only use anastrozole, because it is the only aromatase inhibitor for which we have data. We can postulate that all three aromatase inhibitors will be active and have similar toxicity, but we don’t know that.

In the metastatic setting, letrozole and anastrozole appear to be very similar in both effectiveness and toxicity. Exemestane has really not been well-evaluated, but I would wager that the results will be similar. In the metastatic setting, I don’t have much of a preference for one aromatase inhibitor versus another. There’s been a lot of speculation that letrozole may lead to some amount of adrenal insufficiency. I’m not sure whether that will be true. Exemestane may have a superior safety profile in terms of bone, but we should think about its potential steroidal effects.

We need the adjuvant studies with large numbers of patients to address that issue. We’re not going to get that answer from the metastatic studies, because there have been too few patients.

Potential for aromatase inhibitor use for risk reduction

If we look at the ATAC data, the improvement in terms of contralateral breast cancer risk is impressive. It is over 50 percent better than what we have achieved with tamoxifen. If the prevention trials with the aromatase inhibitors are positive, then the discussion will be easier than it ever was for us with tamoxifen, because tamoxifen was virgin territory. We had to begin with no understanding about chemoprevention. There was a whole process of educating physicians and patients, and that has been done.

The major obstacle for the use of tamoxifen in women at high risk is their fear of endometrial cancer and thrombosis. Some women are concerned about hot flashes and the quality of life issues, but I think when you eliminate those fears, it’ll be much easier to convince women to utilize a chemoprevention strategy.

Clinical trials of adjuvant trastuzumab

The ongoing clinical trials of trastuzumab in the adjuvant, locally advanced and inflammatory settings are likely to give us a lot of information in the next few years. If the data in patients with local disease shows the same results as in the metastatic setting for trastuzumab, it will be an exciting day.

The research question that has to be answered is: How do we use it appropriately? Do we use AC followed by paclitaxel and concurrent trastuzumab, or should we be using a non-anthracycline-containing regimen to avoid cardiac toxicity? Those two questions are going to be very important to address in clinical trials.

I have not been using trastuzumab in the adjuvant setting but have used it for locally advanced and inflammatory disease. I’m selective in choosing patients for whom I’ll use it. Often, it will be the patient who did not respond well to AC or had very aggressive disease.

Management of the chemotherapy-naïve patient with HER2- positive metastatic breast cancer

In patients with metastatic disease who have not previously received chemotherapy, I utilize trastuzumab in combination with chemotherapy. I’m very impressed by the vinorelbine/trastuzumab data. I find it to be a particularly easy regimen, with little toxicity and great effectiveness.

Managing patients with HER2-positive, locally advanced or inflammatory disease

The most difficult patients to manage are those with locally advanced, inflammatory or even locally metastatic disease — the woman with massive tumor in the chest wall, supraclavicular nodes and axillary nodes who has HER2-positive disease. You can treat that woman with trastuzumab/ vinorelbine. The biggest dilemma is: How long do you treat, and at what point do you stop chemotherapy and just continue with trastuzumab? Also, at what point do you stop trastuzumab?

I gave one patient vinorelbine and trastuzumab for about 10 months. She had a fantastic response and went to surgery. At the time of surgery, she had microscopic disease in the breast. I continued the vinorelbine and trastuzumab for another four to six months, and then gave her six months of trastuzumab. It’s totally empiric. I think you could also easily make an argument that this patient should stay on lifelong trastuzumab.

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