title: Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies.
abstract: BACKGROUND
  Treatment decisions in recurrent breast cancer are usually based on the estrogen (ER), progesterone (PgR) and HER2 receptor status of the primary tumour. Retrospective studies suggest that discordance between receptor expression of primary and recurrent breast cancer exists.
  
  
  METHODS
  A pooled analysis of individual patient data from two large prospective studies comprising biopsy of recurrent lesions obtained from consenting patients was undertaken. Tissue was analyzed for ER, PgR by immunohistochemistry and HER2 by FISH. Receptor status of recurrent disease was compared with that of the primary tumour. Recruiting clinicians assessed whether or not receptor discordance affected subsequent systemic treatment.
  
  
  RESULTS
  Two hundred and eighty-nine patients underwent biopsy. Recurrent biopsy specimens were obtained from locoregional recurrence in 48.1% and from distant metastases in 51.9%. Distant sites included skin/soft tissue (25.0%), bone/bone marrow (19.2%) and liver (15.8%). Benign disease or second primary cancer was observed in 7.6% of biopsies. Discordance in ER, PgR or HER2 between confirmed primary and recurrent breast cancer was 12.6%, 31.2% and 5.5%, respectively (all p<0.001). Biopsy results altered management in 14.2% of patients undergoing biopsy (95% confidence intervals 10.4-18.8%, p≤0.0001). The duration between primary and recurrent disease, the site of recurrence and the receptor profile of the primary tumour did not affect discordance rates.
  
  
  CONCLUSIONS
  There is substantial discordance in receptor status between primary and recurrent breast cancer. The number needed to biopsy in order to alter treatment was 7.1. Patients with recurrent breast cancer should have tissue confirmation of receptor status of recurrent disease.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital, The University of Toronto, Toronto, Canada. eitan.amir@uhn.on.ca
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
authors.forename: Colin A
authors.initials: CA
authors.lastname: Purdie
authors.forename: Naomi
authors.initials: N
authors.lastname: Miller
authors.forename: Phil
authors.initials: P
authors.lastname: Quinlan
authors.forename: William
authors.initials: W
authors.lastname: Geddie
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.forename: Orit C
authors.initials: OC
authors.lastname: Freedman
authors.forename: Lee B
authors.initials: LB
authors.lastname: Jordan
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Thompson
mesh_terms: D001706:Biopsy; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology*; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone