The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy

Cancer. 1998 Oct 15;83(8):1529-39.


Background: Histologic grade is well recognized for its prognostic significance in cases of primary operable invasive breast carcinoma; however, the majority of studies in which grade has been assessed have been based on single-center trials. In addition, the role of grade in predicting response to chemotherapy has not been examined in many previous studies.

Methods: The authors assessed the value of Nottingham histologic grade (NHG) in a group of 465 patients enrolled in a multicenter, randomized International Breast Cancer Study Group clinical trial of adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative primary breast carcinoma (formerly named Ludwig Trial V).

Results: NHG was a predictor of overall survival for both LN negative and LN positive patients (P=0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis for both LN positive and LN negative patients, with hazard ratios of 1.651 (P < 0.001) and 1.437 (P=0.045), respectively, for an increase of one grade. Among LN negative patients, this survival disadvantage was observed only for those who received perioperative chemotherapy. For LN positive patients, an increase of one grade resulted in a significant overall survival disadvantage regardless of whether prolonged or perioperative chemotherapy was given. For LN negative patients grouped by grade, there was no observed difference in overall or disease free survival according to whether perioperative chemotherapy or no adjuvant therapy was given. However, LN positive patients with Grade 3 tumors had a significantly greater overall and disease free survival benefit from prolonged chemotherapy than from perioperative chemotherapy (P=0.016 and P=0.013, respectively); LN positive patients with Grade 1 or 2 disease in both treatment arms had comparable overall and disease free survival. A strong correlation between the previously utilized Bloom-Richardson grading system (BRG) and NHG was observed (P < 0.001 and kappa=82%) and no apparent differences in overall and disease free survival were observed between the two systems. NHG did, however, identify a greater proportion of tumors as Grade 1, and BRG identified a greater proportion of breast carcinomas as Grade 3.

Conclusions: This multicenter clinical study confirms the value of histologic grade, and the authors propose that this technique be used to identify Grade 3, LN positive patients who will benefit from prolonged rather than perioperative chemotherapy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Carcinoma / drug therapy
  • Carcinoma / pathology*
  • Carcinoma / surgery
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Estrogen Antagonists / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Forecasting
  • Humans
  • Lymph Nodes / pathology
  • Mastectomy
  • Methotrexate / administration & dosage
  • Neoplasm Invasiveness
  • Postmenopause
  • Prednisone / administration & dosage
  • Premenopause
  • Prognosis
  • Proportional Hazards Models
  • Survival Rate
  • Tamoxifen / administration & dosage


  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Hormonal
  • Estrogen Antagonists
  • Tamoxifen
  • Cyclophosphamide
  • Fluorouracil
  • Prednisone
  • Methotrexate