Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2011

Open Access 01-12-2011 | Research

Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

Authors: Amit Agrawal, John FR Robertson, KL Cheung

Published in: World Journal of Surgical Oncology | Issue 1/2011

Login to get access

Abstract

Background

It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy".

Methods

Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1) estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years), locally advanced or metastatic breast cancer; (2) disease deemed suitable for treatment by hormonal manipulation; (3) disease assessable by UICC criteria; (4) received "withdrawal" from a prior endocrine agent as a form of therapy; (5) on "withdrawal therapy" for ≥ 6 months unless they progressed prior.

Results

Seventeen patients with median age of 84.3 (53.7-92.5) had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10), an aromatase inhibitor (n = 5), megestrol acetate (n = 1) or fulvestrant (n = 1). Ten patients (58.8%) had clinical benefit (CB) (complete response/partial response/stable disease ≥ 6 months) with a median duration of Clinical Benefit (DoCB) of 10+ (7-27) months. Two patients remain on "withdrawal therapy" at the time of analysis.

Conclusion

"Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.
Literature
1.
go back to reference Osborne CK, Shou J, Massarweh S, Schiff R: Crosstalk between Estrogen Receptor and Growth Factor Receptor Pathways as a Cause for Endocrine Therapy Resistance in Breast Cancer. Clinical Cancer Research. 2005, 112: 865s-870s. Osborne CK, Shou J, Massarweh S, Schiff R: Crosstalk between Estrogen Receptor and Growth Factor Receptor Pathways as a Cause for Endocrine Therapy Resistance in Breast Cancer. Clinical Cancer Research. 2005, 112: 865s-870s.
2.
go back to reference Legault-Poisson S, Jolivet J, Poisson R, Beretta-Piccoli M, Band PR: Tamoxifen-induced tumor stimulation and withdrawal response. Cancer Treat Rep. 1979, 6311-12: 1839-1841. Legault-Poisson S, Jolivet J, Poisson R, Beretta-Piccoli M, Band PR: Tamoxifen-induced tumor stimulation and withdrawal response. Cancer Treat Rep. 1979, 6311-12: 1839-1841.
3.
go back to reference Stein W, Hortobagyi GN, Blumenschein GR: Response of metastatic breast cancer to tamoxifen withdrawal: report of a case. J Surg Oncol. 1983, 221: 45-46.CrossRef Stein W, Hortobagyi GN, Blumenschein GR: Response of metastatic breast cancer to tamoxifen withdrawal: report of a case. J Surg Oncol. 1983, 221: 45-46.CrossRef
4.
go back to reference Canney PA, Griffiths T, Latief TN, Priestman TJ: Clinical significance of tamoxifen withdrawal response. Lancet. 1987, 18523: 36-CrossRef Canney PA, Griffiths T, Latief TN, Priestman TJ: Clinical significance of tamoxifen withdrawal response. Lancet. 1987, 18523: 36-CrossRef
5.
go back to reference Belani CP, Pearl P, Whitley NO, Aisner J: Tamoxifen withdrawal response. Report of a case. Arch Intern Med. 1989, 1492: 449-450.CrossRef Belani CP, Pearl P, Whitley NO, Aisner J: Tamoxifen withdrawal response. Report of a case. Arch Intern Med. 1989, 1492: 449-450.CrossRef
6.
go back to reference Howell A, Dodwell DJ, Anderson H, Redford J: Response after withdrawal of tamoxifen and progestogens in advanced breast cancer. Annals Of Oncology: Official Journal Of The European Society For Medical Oncology/ESMO. 1992, 38: 611- Howell A, Dodwell DJ, Anderson H, Redford J: Response after withdrawal of tamoxifen and progestogens in advanced breast cancer. Annals Of Oncology: Official Journal Of The European Society For Medical Oncology/ESMO. 1992, 38: 611-
7.
go back to reference Osipo C, Gajdos C, Cheng D, Jordan VC: Reversal of tamoxifen resistant breast cancer by low dose estrogen therapy. J Steroid Biochem Mol Biol. 2005, 932-5: 249-256.CrossRef Osipo C, Gajdos C, Cheng D, Jordan VC: Reversal of tamoxifen resistant breast cancer by low dose estrogen therapy. J Steroid Biochem Mol Biol. 2005, 932-5: 249-256.CrossRef
8.
go back to reference McClelland RA, Finlay P, Walker KJ, Nicholson D, Robertson JF, Blamey RW, Nicholson RI: Automated quantitation of immunocytochemically localized estrogen receptors in human breast cancer. Cancer Res. 1990, 5012: 3545-3550. McClelland RA, Finlay P, Walker KJ, Nicholson D, Robertson JF, Blamey RW, Nicholson RI: Automated quantitation of immunocytochemically localized estrogen receptors in human breast cancer. Cancer Res. 1990, 5012: 3545-3550.
9.
go back to reference British Breast Group: Assessment of response to treatment in advanced breast cancer. Lancet. 1974, 2: 38-39.CrossRef British Breast Group: Assessment of response to treatment in advanced breast cancer. Lancet. 1974, 2: 38-39.CrossRef
10.
go back to reference Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD: Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer. 1977, 393: 1289-1294.CrossRef Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD: Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer. 1977, 393: 1289-1294.CrossRef
11.
go back to reference Simon WE, Albrecht M, Trams G, Dietel M, Holzel F: In vitro growth promotion of human mammary carcinoma cells by steroid hormones, tamoxifen, and prolactin. J Natl Cancer Inst. 1984, 732: 313-321. Simon WE, Albrecht M, Trams G, Dietel M, Holzel F: In vitro growth promotion of human mammary carcinoma cells by steroid hormones, tamoxifen, and prolactin. J Natl Cancer Inst. 1984, 732: 313-321.
12.
go back to reference Gottardis M, Jordan V: Development of Tamoxifen-stimulated Growth of MCF-7 Tumors in Athymic Mice after Long-Term Antiestrogen Administration. Cancer Res. 1988, 48: 5183-5187.PubMed Gottardis M, Jordan V: Development of Tamoxifen-stimulated Growth of MCF-7 Tumors in Athymic Mice after Long-Term Antiestrogen Administration. Cancer Res. 1988, 48: 5183-5187.PubMed
13.
go back to reference Agrawal A, Robertson JF, Cheung KL: Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents. World J Surg Oncol. 2006, 4: 44-10.1186/1477-7819-4-44.PubMedCentralCrossRefPubMed Agrawal A, Robertson JF, Cheung KL: Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents. World J Surg Oncol. 2006, 4: 44-10.1186/1477-7819-4-44.PubMedCentralCrossRefPubMed
14.
go back to reference Masamura S, Santner SJ, Heitjan DF, Santen RJ: Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. J Clin Endocrinol Metab. 1995, 8010: 2918-2925. Masamura S, Santner SJ, Heitjan DF, Santen RJ: Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. J Clin Endocrinol Metab. 1995, 8010: 2918-2925.
Metadata
Title
Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer
Authors
Amit Agrawal
John FR Robertson
KL Cheung
Publication date
01-12-2011
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2011
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-9-101

Other articles of this Issue 1/2011

World Journal of Surgical Oncology 1/2011 Go to the issue