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Aromatase Inhibitors: Treatment of Advanced Breast Cancer

Jewish General Hospital, Montreal, Quebec, Canada

To the Editor:The report of the superior efficacy of letrozole versus tamoxifen in the first-line treatment of advanced breast cancer in postmenopausal women is an excellent and carefully analyzed randomized trial. It is apparent that letrozole is significantly superior to tamoxifen in terms of time to progression, time to treatment failure, and overall response. It is too early to say whether this treatment will have an effect on survival. As can be noted in Fig 2 of the original report, approximately 20% of the patients are still responding to treated at 2 years.¹

The selective aromatase inhibitors are nontoxic compounds used in the short-term treatment of patients with metastatic breast cancer. However, as one of the participants in the initial trial of letrozole versus megestrol acetate for second-line treatment of breast cancer,² I had a patient who experienced a complete remission on letrozole that lasted approximately 4 years. When that patient experienced relapse, she developed severe back pain. Although there was evidence of metastatic disease in the bones, there was also evidence of osteoporosis. The aromatase inhibitors decrease serum estrogen levels and, theoretically, could accelerate osteoporosis. Have any of the patients on the current study who are still being treated beyond 2 years undergone bone density analysis to determine whether there seems to be an increased incidence of osteoporosis with letrozole versus tamoxifen? If the aromatase inhibitors cause osteoporosis and if there is not difference in survival in your current study, then perhaps it would be more prudent to continue using tamoxifen as first-line hormonal therapy.

REFERENCES

1. Mouridsen H, Gershanovich M, Sun Y, et al: Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: Results of a phase III study of the international letrozole breast cancer group. J Clin Oncol 19: 2596-2606, 2001[Abstract/Free Full Text]

2. Dombernowsky P, Smith I, Falkson G, et al: Letrozole, a new oral aromatase inhibitor for advanced breast cancer: Double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol 15: 453-461, 1998

Response

Rigshospitalet, Copenhagen, Denmark
Novartis Pharma AG, Basel, Switzerland

In Reply:Osteoporosis is not a rare phenomenon in elderly women and may even be more frequent in patients with metastatic breast cancer because of decreased mobility. Although there are concerns as to the potential association between prolonged estrogenic suppression and bone morbidity in terms of osteoporosis/fractures, it should be noted that in postmenopausal women, the magnitude of suppression of estrogens effected by aromatase inhibitors is far smaller than the suppression that occurs when premenopausal women turn postmenopausal. This latter suppression often leads to bone loss and accelerated osteoporosis and possibly fractures.

The current study was not designed specifically to address these concerns. However, osteoporosis was reported as an adverse event in one patient who was treated with tamoxifen. This 64-year-old patient entered the study with three assessable bone lesions and no other disease sites. At 6 months, she complained of lumbar and thoracic bone pain, and osteoporosis was also reported. Treatment with tamoxifen was continued until progression of disease 15 months later. At that time, her treatment was switched to letrozole, with which she is currently being treated.

Another patient, 56 years old when she entered the study, had three soft tissue lesions at baseline and no other site of disease. After 3 years of tamoxifen, symptoms of osteoporosis were reported. Tamoxifen was continued for a further 3 months, at which time progression of disease in soft tissue was diagnosed.

At study entry, 12 patients in the letrozole arm and 18 in the tamoxifen arm had osteoporosis. There was no suggestion that there was a deterioration in the osteoporosis. Our article referred to a median follow-up of approximately 18 months. Further data for approximately another 18 months will be available later this year.

The important question about the impact of prolonged estrogen suppression is being addressed in ongoing adjuvant studies, but so far no valid conclusions can be drawn.

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Panasci, L. C. Articles by Chaudri-Ross, H. A. Search for Related Content PubMed PubMed Citation Articles by Panasci, L. C. Articles by Chaudri-Ross, H. A. Social Bookmarking                            What's this?