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Letters

Raloxifene and breast cancer

Joanne Lorraine
CMAJ October 02, 2001 165 (7) 888;
Joanne Lorraine
Associate Vice President Clinical Research Eli Lilly Canada Inc. Toronto, Ont.
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We wish to acknowledge Kathleen Pritchard and colleagues for bringing to light a number of important issues regarding raloxifene and breast cancer.1

In a recent animal study, the effects of raloxifene on several breast cancer cell lines (which had been implanted into athymic mice) were investigated.2 In the MCF7 (tamoxifen-sensitive) cell line, no significant growth was noted with either tamoxifen or raloxifene. In the MCF7TAMST cell line (a tamoxifen-resistant line exposed to tamoxifen for 5 years) “there was no significant difference between tamoxifen and raloxifene, in combination with E2 [estradiol] on tumor growth.” Neither the method by which study doses were chosen nor the use of a control group of mice was mentioned in the abstract. Although we agree with Pritchard and colleagues that raloxifene would not be the osteoporosis treatment of choice in women with tamoxifen-resistant breast cancer, it is premature to extrapolate the results of limited animal-model studies on the effects of raloxifene on tamoxifen-dependent breast cancer cell lines to disease-free humans.

We do not agree with Pritchard and colleagues that “raloxifene is very similar to tamoxifen.” There are differences in their respective tissue-specific effects that translate into distinct clinical profiles. For example, while tamoxifen (a triphenylethylene compound) has been shown to have stimulatory and carcinogenic effects on the human endometrium,3 raloxifene (a benzothiophene) has been proven to have no adverse effects on the endometrium.4,5 The risk of venous thromboembolic events with raloxifene is similar to that seen with either tamoxifen or hormone replacement therapy.6,7

We agree that raloxifene is not currently indicated for breast cancer prevention and that it should not be used as a substitute for tamoxifen as adjuvant therapy for breast cancer.

Three large ongoing trials involving over 35 000 women, with reduction of breast cancer as the primary endpoint, will help to further clarify the role of raloxifene in the prevention of breast cancer.

References

  1. 1.↵
    Pritchard KI, Levine M, Walley B, on behalf of the Ad Hoc Raloxifene in Breast Cancer Group. Raloxifene: handle with care [letter]. CMAJ 2001;165(2):151-3.
    OpenUrlFREE Full Text
  2. 2.↵
    O'Regan RM, Gajdos S, Dardes R, de los Reyes A, Bentrem DJ, Jordan VC. Effect of raloxifene after tamoxifen on breast and endometrial cancer growth [abstract]. In: Proceedings of the 37th ASCO Annual Meeting; 2001 May 12–15; San Francisco. Abstr. no. 95.
  3. 3.↵
    Bergman L, Beelen MRL, Gallee MPW, Hollema H, Benraadt J, van Leeuwen FE. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Lancet 2000; 356:881-7.
    OpenUrlCrossRefPubMed
  4. 4.↵
    Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW, et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple Outcomes of Raloxifene Evaluation. Breast Cancer Res Treat 2001;65:125-34.
    OpenUrlCrossRefPubMed
  5. 5.↵
    Cohen FJ, Watts S, Shah A, Akers R, Plouffe L Jr. Uterine effects of 3-year raloxifene therapy in postmenopausal women younger than age 60. Obstet Gynecol 2000;95:104-10.
    OpenUrlCrossRefPubMed
  6. 6.↵
    Grady D, Wenger NK, Herrington D, Khan S, Furberg C, Hunninghake D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2000;132:689-96.
    OpenUrlPubMed
  7. 7.↵
    Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90:1371-88.
    OpenUrlAbstract/FREE Full Text
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CMAJ
Vol. 165, Issue 7
2 Oct 2001
  • Table of Contents
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  • Canadian Adverse Drug Reaction Newsletter (942-949)

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