title: Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group.
abstract: Neoadjuvant systemic therapy is being used increasingly in the treatment of early-stage breast cancer. Response, in the form of pathological complete response, is a validated and evaluable surrogate end point of survival after neoadjuvant therapy. Thus, pathological complete response has become a primary end point for clinical trials. However, there is a current lack of uniformity in the definition of pathological complete response. A review of standard operating procedures used by 28 major neoadjuvant breast cancer trials and/or 25 sites involved in such trials identified marked variability in specimen handling and histologic reporting. An international working group was convened to develop practical recommendations for the pathologic assessment of residual disease in neoadjuvant clinical trials of breast cancer and information expected from pathology reports. Systematic sampling of areas identified by informed mapping of the specimen and close correlation with radiological findings is preferable to overly exhaustive sampling, and permits taking tissue samples for translational research. Controversial areas are discussed, including measurement of lesion size, reporting of lymphovascular space invasion and the presence of isolated tumor cells in lymph nodes after neoadjuvant therapy, and retesting of markers after treatment. If there has been a pathological complete response, this must be clearly stated, and the presence/absence of residual ductal carcinoma in situ must be described. When there is residual invasive carcinoma, a comment must be made as to the presence/absence of chemotherapy effect in the breast and lymph nodes. The Residual Cancer Burden is the preferred method for quantifying residual disease in neoadjuvant clinical trials in breast cancer; other methods can be included per trial protocols and regional preference. Posttreatment tumor staging using the Tumor-Node-Metastasis system should be included. These recommendations for standardized pathological evaluation and reporting of neoadjuvant breast cancer specimens should improve prognostication for individual patients and allow comparison of treatment outcomes within and across clinical trials.
authors.affiliation: Department of Histopathology and NIH Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Provenzano
authors.affiliation: Department of Pathology, Yale University, New Haven, CT, USA.
authors.forename: Veerle
authors.initials: V
authors.lastname: Bossuyt
authors.affiliation: Department of Pathology, European Institute of Oncology and University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Edinburgh Cancer Research UK Centre,University of Edinburgh, Edinburgh, UK.
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Badve
authors.affiliation: Institute of Pathology, Charité Hospital, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.affiliation: Department of Biopathology, Institut Bergonié, Bordeaux, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: MacGrogan
authors.affiliation: Department of Pathology, Centre Jean Perrin and Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Penault-Llorca
authors.affiliation: Division of Subspecialty General Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Boughey
authors.affiliation: Early Drug Development for Innovative Therapies Division, European Institute of Oncology, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: Edinburgh Breast Unit, Western General Hospital, Edinburgh, UK.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Dixon
authors.affiliation: Carol Franc Buck Breast Care Center, University of California, San Francisco, CA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Esserman
authors.affiliation: Department of Radiotherapy and Radiation Oncology, Landeskrankenhaus, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Fastner
authors.affiliation: Department of Gynecology and Obstetrics, Interdisciplinary Breast Center, Klinikum Esslingen, Esslingen, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kuehn
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.|Department of Gynecology, General Hospital Leoben, Leoben, Austria.
authors.forename: Florentia
authors.initials: F
authors.lastname: Peintinger
authors.affiliation: German Breast Group, Neu-Isenburg, and Department of Gynecology and Obstetrics, University Women's Hospital, Frankfurt, Germany.
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.affiliation: Department of Radiation Oncology, Ohio State University, Columbus, OH, USA.
authors.forename: Julia
authors.identifier: http://orcid.org/0000-0001-6624-5631
authors.initials: J
authors.lastname: White
authors.affiliation: Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy; D002986:Clinical Trials as Topic / Q000592:standards*; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D010338:Pathology, Clinical / Q000592:standards*; D012107:Research Design / Q000592:standards*; D013048:Specimen Handling / Q000592:standards*