title: Effect of neoadjuvant chemotherapy on breast cancer phenotype, ER/PR and HER2 expression - Implications for the practising oncologist.
abstract: To assess the effect of neoadjuvant chemotherapy (NACT) on breast cancer characteristics, hormone receptors and human epidermal growth factor receptor 2 (HER2) expression and whether testing should be repeated on residual tumours.
  
  
  
  Patients with primary operable breast cancer who received NACT at a single United Kingdom tertiary referral centre were included. Tumour type, grade (including details of mitotic grade, tubule formation and pleomorphism), oestrogen receptor (ER), progesterone receptor (PR) and HER2 status were compared between pre-treatment and post-treatment residual samples using tissue microarrays. A control group of paired core and excision tumours from patients who did not receive NACT was also assessed.
  
  
  
  Two hundred forty-six cases and 113 controls were included. Pathological complete response (path CR) was achieved in 21.5% of patients. In those patients failing to achieve a path CR, a change in the histological type was noted in 29 out of 178 cases (16.3%, p<0.001) with increase in the lobular and metaplastic types. Downgrading occurred in 28.8%, due to significant reduction in mitotic rate and prominent tubule formation. A change in ER/PR/HER2 status occurred in 12%, 14.5% and 7.1% of cases, respectively, predominantly as a switch from negative to positive status for ER and from positive to negative status for HER2. Further alterations in expression levels were also noted. Minimal changes in the low ER/PR expressors and the HER2 2+ tumours were found in the control group.
  
  
  
  Significant changes in tumour morphology, grade, hormone receptors and HER2 status occur following NACT. We recommend testing on residual invasive carcinoma. A switch from negative to positive status warrants offering endocrine/trastuzumab-based therapy to this group of patients.
authors.affiliation: Histopathology, St James's Institute for Oncology, St James's University Hospital, Leeds, UK.
authors.forename: Renu
authors.initials: R
authors.lastname: Gahlaut
authors.affiliation: Histopathology, St James's Institute for Oncology, St James's University Hospital, Leeds, UK.
authors.forename: Aneliese
authors.initials: A
authors.lastname: Bennett
authors.affiliation: Breast Surgery, St James's Institute for Oncology, St James's University Hospital, Leeds, UK.
authors.forename: Hiba
authors.initials: H
authors.lastname: Fatayer
authors.affiliation: Imaging and Breast Screening, St James's University Hospital, Leeds, UK.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Dall
authors.affiliation: Imaging and Breast Screening, St James's University Hospital, Leeds, UK.
authors.forename: Nisha
authors.initials: N
authors.lastname: Sharma
authors.affiliation: St James's Institute for Oncology, St James's University Hospital, Leeds, UK.
authors.forename: Galina
authors.initials: G
authors.lastname: Velikova
authors.affiliation: St James's Institute for Oncology, St James's University Hospital, Leeds, UK; Leeds Institute of Cancer Medicine and Pathology, St James's Institute of Oncology, St James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Perren
authors.affiliation: St James's Institute for Oncology, St James's University Hospital, Leeds, UK.
authors.forename: David
authors.initials: D
authors.lastname: Dodwell
authors.affiliation: Breast Surgery, St James's Institute for Oncology, St James's University Hospital, Leeds, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Lansdown
authors.affiliation: Pathology, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre and the University of Birmingham, Birmingham, UK; University of Tanta, Egypt. Electronic address: abeer.shaaban@uhb.nhs.uk.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Shaaban
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D018365:Neoplasm, Residual; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D000068878:Trastuzumab / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast cancer; HER2; Neoadjuvant chemotherapy; Oestrogen receptor; Progesterone receptor