title: Prior Adjuvant Tamoxifen Treatment in Breast Cancer Is Linked to Increased AIB1 and HER2 Expression in Metachronous Contralateral Breast Cancer.
abstract: OBJECTIVE
  The estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamoxifen for the first tumor as an "in vivo"-model for tamoxifen resistance. AIB1-expression in the presumable resistant (CBC after prior tamoxifen) and naïve setting (CBC without prior tamoxifen) is compared and correlated to prognosis after CBC.
  
  
  METHODS
  From a well-defined population-based cohort of CBC-patients we have constructed a unique tissue-microarray including >700 patients.
  
  
  RESULTS
  CBC developed after adjuvant tamoxifen more often had a HER2-positive/triple negative-subtype and a high AIB1-expression (37% vs. 23%, p = 0.009), than if no prior endocrine treatment had been administered. In patients with an estrogen receptor (ER) positive CBC, a high AIB1-expression correlated to an inferior prognosis. However, these patients seemed to respond to tamoxifen, but only if endocrine therapy had not been administered for BC1.
  
  
  CONCLUSIONS
  Metachronous CBC developed after prior endocrine treatment has a decreased ER-expression and an increased HER2-expression. This is consistent with endocrine treatment escape mechanisms previously suggested, and indicates metachronous CBC to be a putative model for studies of treatment resistance "in vivo". The increased AIB1-expression in CBC developed after prior tamoxifen suggests a role of AIB1 in endocrine treatment resistance. In addition, we found indications that the response to tamoxifen in CBC with a high AIB1-expression seem to differ depending on previous exposure to this drug. A different function for AIB1 in the tamoxifen treatment naïve vs. resistant setting is suggested, and may explain previously conflicting results where a high AIB1-expression has been correlated to both a good response to adjuvant tamoxifen and tamoxifen resistance.
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Medicon Village, SE-223 63, Lund, Sweden.|Skåne Clinic of Oncology, Skåne University Hospital Lund, SE-222 41, Lund, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Alkner
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Medicon Village, SE-223 63, Lund, Sweden.
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Medicon Village, SE-223 63, Lund, Sweden.|Department of Pathology and Cytology, Blekinge County Hospital, SE-371 85, Karlskrona, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ehinger
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Medicon Village, SE-223 63, Lund, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lövgren
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Medicon Village, SE-223 63, Lund, Sweden.|Clinic of Surgery, Skåne University Hospital Lund, SE-222 41, Lund, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Medicon Village, SE-223 63, Lund, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D056921:Nuclear Receptor Coactivator 3; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; C538866:NCOA3 protein, human