title: Back to Basics: Traditional Nottingham Grade Mitotic Counts Alone are Significant in Predicting Survival in Invasive Breast Carcinoma.
abstract: BACKGROUND
  Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed.
  
  
  METHODS
  Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2-) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1-3 based on observed mitoses.
  
  
  RESULTS
  A total of 1292 ER+, HER2- invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0-14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p < 0.001), and overall survival/OS (p = 0.01) with higher mitotic scores associated with worse outcomes. Higher mitotic score correlated significantly with intermediate/high risk Oncotype Dx recurrence scores (p = 0.009).
  
  
  CONCLUSIONS
  First-generation molecular profiling assays for estrogen receptor positive invasive breast carcinomas derive much of their predictive power from quantifying genes of proliferation into a single score. Sometimes overlooked in the profusion of molecular data, the time-tested, mitotic count in the Nottingham combined histological grade is a good single-parameter predictor of survival.
authors.affiliation: Department of Surgery, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Chang
authors.affiliation: Department of Pathology, Mayo Clinic, Phoenix, AZ, USA. mccullough.ann@mayo.edu.
authors.forename: Ann E
authors.initials: AE
authors.lastname: McCullough
authors.affiliation: Section of Biostatistics, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Amylou C
authors.initials: AC
authors.lastname: Dueck
authors.affiliation: Section of Biostatistics, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Kosiorek
authors.affiliation: Department of Pathology, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Idris T
authors.initials: IT
authors.lastname: Ocal
authors.affiliation: Department of Pathology, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Lidner
authors.affiliation: Department of Surgery, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gray
authors.affiliation: Department of Surgery, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Nabil
authors.initials: N
authors.lastname: Wasif
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Northfelt
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA.|Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.affiliation: Department of Surgery, Mayo Clinic, Phoenix, AZ, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Pockaj
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D008938:Mitosis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human