title: Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer.
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.
  
  
  CONCLUSIONS
  "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.
authors: Division of Breast Surgery, GEM School, University of Nottingham, Royal Derby Hospital, Derby DE22 3NE, UK. amit.agrawal@nottingham.ac.uk
authors: Amit
authors: A
authors: Agrawal
authors: John F R
authors: JF
authors: Robertson
authors: K L
authors: KL
authors: Cheung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000097:blood*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D013629:Tamoxifen