title: Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21,755 patients from the Japanese breast cancer registry.
abstract: BACKGROUND
  We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data.
  
  
  METHODS
  Records of more than 300,000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21,755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization.
  
  
  RESULTS
  pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10,973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward.
  
  
  CONCLUSIONS
  We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.
authors.affiliation: Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Isehara niikura@is.icc.u-tokai.ac.jp.
authors.forename: N
authors.initials: N
authors.lastname: Niikura
authors.affiliation: Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: A
authors.initials: A
authors.lastname: Tomotaki
authors.affiliation: Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama.
authors.forename: T
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Department of Breast Surgery, Miyagi Cancer Center, Natori.
authors.forename: M
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Department of Surgery, Kitakyushu Municipal Medical Center, Kitakyushu.
authors.forename: K
authors.initials: K
authors.lastname: Anan
authors.affiliation: Department of Breast Surgery, St Luke's International Hospital, Tokyo.
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Breast Surgery, Shikoku Cancer Center, Matsuyama.
authors.forename: K
authors.initials: K
authors.lastname: Aogi
authors.affiliation: Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Sendai.
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Sapporo-kotoni Breast Clinic, Sapporo.
authors.forename: H
authors.initials: H
authors.lastname: Masuoka
authors.affiliation: Department of Breast Oncology, Cancer Institute Hospital, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Department of Pathology, Nihon University School of Medicine, Tokyo.
authors.forename: S
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, St Marianna University School of Medicine, Kawasaki.
authors.forename: K
authors.initials: K
authors.lastname: Tsugawa
authors.affiliation: Department of Breast Surgery, National Cancer Center Hospital, Tokyo.
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Isehara.
authors.forename: Y
authors.initials: Y
authors.lastname: Tokuda
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012042:Registries; D000068878:Trastuzumab / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2; breast cancer; chemotherapy; in situ hybridization; neoadjuvant therapy