title: Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy.
abstract: OBJECTIVE
  A contralateral breast cancer (CBC) is today treated as an independent primary tumour, although recent data suggest risk and prognosis of CBC to be influenced by characteristics of and treatment given for the first tumour (BC1). We hereby investigate phenotypical and prognostic features of the second tumour (BC2) in relation to prior endocrine treatment and radiotherapy.
  
  
  METHODS
  From a well-defined population-based cohort of CBC-patients, we have constructed a unique tissue-microarray including 600 pairs of primary tumours and CBCs. Breast cancer mortality was primary end-point for prognosis.
  
  
  RESULTS
  Both oestrogen receptor (ER) status and stage was strongly correlated between BC1 and BC2 within CBC-pairs. Although BC2 had the highest prognostic impact, BC1 continued to influence prognosis after diagnosis of CBC. Patients diagnosed with two high stage tumours within a short time-interval had a particularly bad prognosis. Prior endocrine therapy and radiotherapy both correlated to ER-negativity of BC2. An ER-negative BC2 was associated with an inferior prognosis compared to an ER-positive BC2 regardless of ER-status of BC1 or prior endocrine therapy.
  
  
  CONCLUSIONS
  Our results suggest that both the residual prognostic impact of BC1, the possibility of contralateral metastasis, as well as prior treatment given, need to be considered when determining appropriate diagnostic work-up and treatment of CBC. In addition, radiation to the contralateral breast and risk of inducing CBC with an aggressive ER-negative phenotype should be considered when establishing new radiation treatment techniques. This study indicates loss of ER-expression as an important 'endocrine treatment escape mechanism', although further studies are warranted.
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences Lund, Lund University Medicon Village, 223 63 Lund, Sweden; Skåne Clinic of Oncology, Skåne University Hospital Lund, 222 41 Lund, Sweden. Electronic address: Sara.Alkner@med.lu.se.
authors.forename: Sara
authors.initials: S
authors.lastname: Alkner
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences Lund, Lund University Medicon Village, 223 63 Lund, Sweden; Department of Pathology and Cytology, Blekinge County Hospital, 371 85 Karlskrona, Sweden. Electronic address: anna.ehinger@med.lu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Ehinger
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences Lund, Lund University Medicon Village, 223 63 Lund, Sweden. Electronic address: Par-Ola.Bendahl@med.lu.se.
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences Lund, Lund University Medicon Village, 223 63 Lund, Sweden; Clinic of Surgery, Skåne University Hospital Lund, 222 41 Lund, Sweden. Electronic address: Lisa.Ryden@med.lu.se.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences Lund, Lund University Medicon Village, 223 63 Lund, Sweden. Electronic address: Marten.Ferno@med.lu.se.
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000009:adverse effects; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis; D012042:Registries; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: Breast neoplasms; Hormonal antineoplastic agents; Humans; Neoplasm staging; Oestrogen receptor; Progesterone receptor; Prognosis; Radiotherapy; Tamoxifen; Tissue microarray analysis