This paper is only available as a PDF. To read, Please Download here.
Abstract
Background: Hormonal therapy (HT) is an important consideration in the management of postmenopausal
women with metastatic breast cancer. Despite the fact that the advanced-stage disease
is virtually incurable, HTs can offer patients disease control equivalent to that
of chemotherapy, but with improved quality of life (QOL). Knowledge of the estrogen
and progesterone receptor status, as well as other clinical factors, allows for selection
of patients who are most likely to benefit from HT. Disease that becomes refractory
to an initial HT may respond to another agent or class of HTs. Thus, HTs are generally
administered sequentially, delaying the need for cytotoxic chemotherapy, which often
reduces QOL. Optimal sequencing is thus one of the more important facets of HT. Prior
to the release of a number of newer agents, tamoxifen had been considered as initial
HT. At present, more agents exist, including the aromatase inhibitors, progestins,
and the estrogen receptor antagonist fulvestrant.
Objective: This article reviews key trials evaluating the use of sequential HTs.
Methods: Articles were identified for inclusion in this manuscript through the following searches,
limited to English-language publications: MEDLINE (mid 1960s to January 2002), American
Society of Oncology abstracts (1997–2001), and San Antonio Breast Cancer Symposium
abstracts (2001 and 2002). The following search terms were used: breast cancer, hormonal therapies, tamoxifen, toremifene, letrozole, anastrozole,
exemestane, megestrol acetate, fulvestrant, and ICI 182,780.
Results: Results of Phase III studies have shown many of these agents to be equivalent or
superior to tamoxifen and can be used initially to treat patients who either have
failed tamoxifen therapy or may be unable to tolerate some of the toxicities associated
with tamoxifen. For example, the aromatase inhibitors have been shown to be highly
active and tolerable in postmenopausal women with breast cancer who have failed tamoxifen
therapy or who are naive to HT. Other clinical trials have demonstrated the efficacy
of fulvestrant in patients with metastatic breast cancer who are tamoxifen-resistant,
and have shown fulvestrant to be at least as effective as anastrozole in tamoxifen-resistant
patients.
Conclusions: Although the optimum sequence of HTs remains controversial, using the newer agents
as initial or subsequent therapy should improve QOL and may improve overall survival.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical TherapeuticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A new anti-oestrogenic agent in late breast cancer: An early clinical appraisal of ICI46474.Br J Cancer. 1971; 25: 270-275
- Aminoglutethimide (Elipten-Ciba) as an inhibitor of adrenal steroidogenesis: Mechanism of action and therapeutic trial.J Clin Endocrinol Metab. 1967; 27: 1239-1248
- Basic guides to the mechanism of estrogen action.Recent Prog Horm Res. 1962; 18: 387-414
- The role of progestins and progesterone receptors in the treatment of breast cancer.Steroids. 1984; 44: 467-484
- Endocrine therapy in the treatment of metastatic breast cancer.Semin Oncol. 2001; 28: 291-304
- Tamoxifen for early breast cancer: An overview of the randomised trials.Lancet. 1998; 351 (Early Breast Cancer Trialists' Collaborative Group): 1451-1467
- 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: 1371-1388
- The effect of raloxifene on risk of breast cancer in postmenopausal women: Results from the MORE randomized trial. Multiple Outcomes of Raloxifene Eval.JAMA. 1999; 281: 2189-2197
- Endocrine therapies of breast cancer.Semin Oncol. 1996; 23: 494-505
- Mechanisms of action of endocrine treatment in breast cancer.Crit Rev Oncol Hematol. 1995; 21: 158-193
- Response to third-line endocrine treatment for advanced breast cancer.Eur J Cancer. 1993; 29A: 572-574
- Second and third line hormonotherapy in advanced post-menopausal breast cancer: A multicenter randomized trial comparing medroxyprogesterone acetate wi.Breast Cancer Res Treat. 1993; 24: 139-145
- Aromatase inhibition with 4-OHAndrostenedione after prior aromatase inhibition with aminoglutethimide in women with advanced breast cancer.Breast Cancer Res Treat. 1995; 35: 249-253
- Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: A phase II multi.Eur J Cancer. 1997; 33 (Exemestane Study Group): 1767-1773
- Comparison of tamoxifen and hypophysectomy in breast cancer treatment.Cancer. 1980; 45: 1322-1325
- Endocrine therapies for patients with recurrent breast cancer: Predictive factors for responses to first- and second-line endocrine therapies.Oncology. 2000; 59: 31-37
- Endocrine treatment of breast cancer.in: Becker KL Principles and Practice of Endocrinology and Metabolism. 2nd ed. JB Lippincott, Philadelphia1995: 1868-1875
- Multicenter phase II efficacy trial of toremifene in tamoxifen-refractory patients with advanced breast cancer.J Clin Oncol. 1993; 11: 345-350
- Toremifene and tamoxifen in advanced breast cancer: A double-blind cross-over trial.Breast Cancer Res Treat. 1993; 25: 57-63
- Current status and controversial issues concerning endocrine therapy for patients with recurrent breast cancer in Japan.Breast Cancer. 1999; 6: 344-350
- National Institutes of Health Consensus Development Conference Statement: Adjuvant therapy for breast cancer, November 1–3, 2000.J Natl Cancer Inst. 2001; 93: 979-989
- The Complete Library of NCCN Oncology Practice Guidelines [CD-ROM].NCCN Breast Cancer Guideline, version 2.2002. February 1, 2002 (Accessed)
- Adjuvant therapy of primary breast cancer: A review of key findings from the 7th International Conference.in: St. Gallen, February 2001Oncologist. 6. 2001: 376-385
- Hormonal treatment of advanced breast cancer.in: Kennedy BJ Breast Cancer. Current Clinical Oncology. Vol. 1. Alan R. Liss, New York1989: 163-172
- Hormonal treatment for metastatic breast cancer. An Eastern Cooperative Oncology Group phase III trial comparing amino-glutethimide to tamoxifen.Cancer. 1994; 73: 354-361
- Aromatase inhibitors in malignant diseases of aging.Drugs Aging. 1992; 2: 530-545
- Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: Results of a survival update based on a c.Cancer. 1998; 83 (Arimidex Study Group): 1142-1152
- Letrozole, a new oral aromatase inhibitor for advanced breast cancer: Double-blind randomized trial showing a dose effect and improved efficacy and tol.J Clin Oncol. 1998; 16: 453-461
- Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: Results of a phase III randomi.J Clin Oncol. 2000; 18 (Examestane Study Group): 1399-1411
- Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma.Cancer. 2001; 92: 2247-2258
- Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: Results of a phase III stud.J Clin Oncol. 2001; 19: 2596-2606
- Fulvestrant.Drugs. 2001; 61 (Discussion 814): 807-813
- Progestational agents in advanced breast cancer: An overview.Semin Oncol. 1986; 13: 2-8
- Megestrol acetate versus medroxyprogesterone acetate in the treatment of metastasizing breast cancers: Intermediate report of a multicenter phase III s.Onkologie. 1987; 10: 104-106
- Tamoxifen versus high-dose oral medroxy-progesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: A Piedmont Oncolo.J Clin Oncol. 1994; 12: 1630-1638
- A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer.Eur J Cancer. 1996; 32A (Abstract): 1888-1892
- Second-line endocrine treatment of advanced breast cancer: A randomized cross-over study of medroxy-progesterone acetate and aminoglutethimide.Acta Oncol. 1996; 35: 75
- Fulvestrant.Expert Opin Investig Drugs. 2002; 11: 303-308
- Greater duration of response with Faslodex® (fulvestrant) injection compared to Arimidex (anastrozole) in postmenopausal women with advanced breast c.Abstract presented at the American Association for Cancer Research 93rd Annual Meeting. April 6–10, 2002 (San Francisco, Calif.)
- for the Faslodex Trial 0020 and 0021 Investigators. Evidence of continued sensitivity to endocrine agents in postmenopausal women with advanced breast.Program and Abstracts of the 24th Annual San Antonio Breast Cancer Symposium. December 10–13, 2001 (San Antonio, Tex. Abstract 446)
- Randomized trial of estrogen vs. tamoxifen therapy for advanced breast cancer.Am J Clin Oncol. 1985; 8: 128-133
- The tamoxifen trial: A double-blind comparison with stilboestrol in postmenopausal women with advanced breast cancer.Eur J Cancer. 1980; : 83-88
- A clinical trial to compare the use of tamoxifen vs. stilboestrol in the treatment of postmenopausal women with advanced breast cancer.Rev Endocr Relat Cancer. 1981; : 409-414
- Tamoxifen and fluoxymesterone in advanced breast cancer: A controlled clinical trial.Cancer Treat Rep. 1980; 64: 117-121
Article info
Publication history
Accepted:
April 2,
2002
Identification
Copyright
© 2002 Published by Elsevier Inc.
