title: Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial.
abstract: BACKGROUND
  When the mechanism of action behind treatment toxicity reflects the intended effect on the treatment target, the toxicity might be a useful marker for efficacy. During endocrine treatment of breast cancer, the occurrence of symptoms related to oestrogen depletion or oestrogen blockade might thus be a predictor of treatment effectiveness. In this retrospective analysis, the relation between the reported incidence of vasomotor or joint symptoms and breast cancer recurrence in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial is assessed.
  
  
  METHODS
  Women with hormone-receptor-positive tumours who reported vasomotor or joint symptoms at the first follow-up visit (3 months) in the ATAC trial, (which assessed tamoxifen or anastrozole for adjuvant treatment of postmenopausal breast cancer), were compared with women without these symptoms to see if there was a relation between these symptoms and subsequent recurrence. The ATAC trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230.
  
  
  RESULTS
  1486 of 3964 (37.5%) eligible women reported newly emergent vasomotor symptoms at the 3-month follow-up visit and had lower subsequent recurrence than those who did not report these symptoms (223 during 10 752 women-years of follow-up vs 366 during 11 573 woman-years of follow-up, respectively; hazard ratio [HR] 0.84 [95% CI 0.71-1.00], p=0.04; adjusted for age, body-mass index, previous hormone-replacement therapy, nodal status, tumour size, and tumour grade). A greater decrease in breast-cancer recurrence was seen for the 1245 of 3964 (31.4%) eligible women who reported new joint symptoms at the 3-month follow-up visit compared with those not reporting these symptoms (158 during 9242 women-years of follow-up vs 366 during 11 573 women-years of follow-up; adjusted HR 0.60 [0.50-0.72], p<0.0001).
  
  
  CONCLUSIONS
  The appearance of new vasomotor symptoms or joint symptoms within the first 3 months of treatment is a useful biomarker, suggesting a greater response to endocrine treatment compared with women without these symptoms. Awareness of the relation between early treatment-emergent symptoms and beneficial response to therapy might be useful when reassuring patients who present with them, and might help to improve long-term treatment adherence when symptoms cannot be alleviated effectively.
authors.affiliation: Cancer Research UK, Centre for Epidemiology, Mathematics, and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary School of Medicine and Dentistry, University of London, London, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: Ivana
authors.initials: I
authors.lastname: Sestak
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.forename: Lesley
authors.initials: L
authors.lastname: Fallowfield
mesh_terms: D000328:Adult; D000368:Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D018771:Arthralgia / Q000139:chemically induced*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D005260:Female; D019584:Hot Flashes / Q000139:chemically induced*; D006801:Humans; D007596:Joints / Q000187:drug effects*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000188:drug therapy*; D009570:Nitriles / Q000009:adverse effects; D016017:Odds Ratio; D017698:Postmenopause; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D013629:Tamoxifen / Q000009:adverse effects; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects; D014666:Vasomotor System / Q000187:drug effects*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole