FIRST-LINE ENDOCRINE THERAPY OF PREMENOPAUSAL WOMEN

The question of whether tamoxifen is superior, equivalent or inferior to GnRH agonists is sort of unanswerable. This patient’s family thrombosis history aside, my inclination in general is to use GnRH analogs, because they assure compliance. Using hormonal therapies in sequence is the best way to treat estrogen-sensitive breast cancer. Leuprolide or goserelin followed by tamoxifen always made more sense to me than the opposite.

There are two clinical trials that compared goserelin plus tamoxifen to tamoxifen alone, and there was a pooled analysis of the two studies ^40-42. The rates of response with combination therapy are generally higher but so are the toxicities. The survival rates might also be slightly longer with the combination, but we don’t know what sequence of hormonal therapies the control groups received. I would submit that if someone did a pure endocrine study of Drug A plus Drug B versus Drug A followed by Drug B, you probably wouldn’t see a significant difference in outcome. The second arm of that study — Drug A followed by Drug B — is virtually guaranteed to have less toxicity. Based on the available information, I still have not jumped into the combined hormonal therapy camp.

—Kevin Fox, MD

Tamoxifen would usually be my first-line hormonal intervention in a premenopausal woman with metastatic disease. In this case, the family history of pulmonary emboli would give me pause. Although her family history raises a red flag, because her coagulation workup was negative, in my opinion tamoxifen is not contraindicated.

—Patricia Madej, MD

Based on the first-line data of AIs versus tamoxifen in metastatic breast cancer ^43-45, my strategy would be to suppress ovarian function and put her on an AI rather than to use tamoxifen, because I think these agents work better for metastatic disease. Ovarian suppression can be done with an LH-RH agonist or oophorectomy — that’s up to each individual patient. Younger women often don’t want immediate oophorectomy — I think that an LH-RH agonist is a good way to bridge the gap.

—Stephen Jones, MD

CHOOSING ANOTHER ENDOCRINE THERAPY

I chose anastrozole in this case because of the patient’s family history of pulmonary emboli in two siblings. I worked her up for a thrombophilia and found none of the common causes. But, in this patient with an undefinable propensity towards thrombosis based on a family history, I thought it most prudent to prescribe the least thrombogenic hormonal therapy compared to tamoxifen — in this case, anastrozole ^46-48.

—Kevin Fox , MD

In this particular scenario, I would consider another hormonal intervention. She’s clearly shown a response clinically for a significant duration, so another hormonal intervention could be considered. Probably at this point, our next step would be to add an aromatase inhibitor. They are well-tolerated, and there is measurable efficacy in hormone receptor-positive patients.

—Patricia Madej, MD

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