title: Breast cancer during follow-up and progression - A population based cohort on new cancers and changed biology.
abstract: BACKGROUND
  Emerging data indicate an important role for biopsies of clinically/radiologically defined breast cancer 'recurrences'. The present study investigates tumour related events (relapses, other malignancies, benign conditions) after a primary breast cancer diagnosis.
  
  
  METHODS
  The cohort includes 2102 women, representing all patients, with primary invasive breast cancer during 2000-2011 in the county of Värmland, Sweden. A comparative analysis of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation (Ki67) between the primary tumour and the relapse was performed and related to outcome.
  
  
  RESULTS
  With a mean follow-up time of 4.8 years, 1060 out of 2102 patients have had a biopsy taken after the initial breast cancer diagnosis demonstrating 177 recurrences, 93 other malignancies (colorectal, lung, skin), 40 cancer in situ (skin, breast) and 857 benign lesions. Approximately 70% (177 out of 245) of all cases of relapsed breast cancer underwent a biopsy during this time period. For patients with recurrences, ER (n=127), PR (n=101), HER2 (n=73) and Ki67 (n=55) status in both primary tumour and the corresponding relapse were determined. The discordance of receptor status was 14.2%, 39.6%, 9.6% and 36.3%, respectively. Loss of ER or PR in the relapse resulted in a significant increased risk of death (hazard ratio (HR) 3.62; 95% confidence interval (CI), 1.65-7.94) and (HR 2.34; 95% CI, 1.01-5.47) compared with patients with stable ER or PR positive tumours. The proportion of patients losing ER was bigger in the group treated with endocrine therapy alone or in combination with chemotherapy, 16.7% and 13.3%, respectively, compared with the group treated with chemotherapy alone or that which received no treatment 4.3% and 7.7%, respectively.
  
  
  CONCLUSIONS
  Discordance of biomarkers between the primary tumour and the corresponding relapse was seen in 10-40% of the patients, adjuvant therapies seem to drive clonal selections. Patients with tumours losing ER or PR during progression have worse survival compared with patients with retained receptor expression.
authors.affiliation: Department of Oncology-Pathology, Radiumhemmet, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm, Sweden; Department of Oncology, Central Hospital Karlstad, Sweden. Electronic address: eva.karlsson@ki.se.
authors.forename: E
authors.initials: E
authors.lastname: Karlsson
authors.affiliation: Department of Economics and Statistics, Karlstad University, Karlstad, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Appelgren
authors.affiliation: Department of Pathology, Central Hospital Karlstad, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Solterbeck
authors.affiliation: Department of Surgery, Central Hospital Karlstad, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bergenheim
authors.affiliation: Department of Oncology, Central Hospital Karlstad, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Alvariza
authors.affiliation: Department of Oncology-Pathology, Radiumhemmet, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Bergh
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D059186:Chemoradiotherapy, Adjuvant; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D016609:Neoplasms, Second Primary / Q000378:metabolism / Q000401:mortality*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D013548:Sweden / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Biomarker; Breast cancer; Human epidermal growth factor receptor 2; Oestrogen receptor; Progesterone receptor