Long-Term Outcomes of Immunohistochemically Defined Subtypes of Breast Cancer Less Than or Equal to 2 cm After Breast-Conserving Surgery

J Surg Res. 2019 Apr:236:288-299. doi: 10.1016/j.jss.2018.11.028. Epub 2018 Dec 27.

Abstract

Background: Molecular subtype predicts the prognosis of early-stage breast cancer patients. We assessed the long-term outcomes of breast cancer ≤2 cm treated with breast-conserving surgery (BCS) and stratified according to an immunohistochemically (IHC)-based subtype definition.

Methods: This retrospective study was conducted from a prospectively collected database. Included patients had pT1, any N, M0 breast cancer after BCS (without anti-HER2 therapy) and available information on estrogen receptor (ER), progesterone receptor (PR), HER2 status, Ki-67 index. Five IHC-defined subtypes were identified: luminal A-like (ER and/or PR-positive/HER2-negative/Ki-67 < 20%), luminal B-like/HER2-negative (ER and/or PR-positive/HER2-negative/Ki-67 ≥ 20%), luminal B-like/HER2-positive (ER and/or PR-positive/HER2-positive/any Ki-67 value), HER2-positive/nonluminal (ER and PR-negative/HER2-positive), and triple-negative (ER and PR-negative/HER2-negative).

Results: We analyzed 184 (65%) luminal A-like, 57 (20%) luminal B-like/HER2-negative, 17 (6%) luminal B-like/HER2-positive, 6 (2%) HER2-positive/nonluminal, and 18 (7%) triple-negative patients. Median follow-up was 112 (interquartile range 94-125) mo. The cumulative 5- and 10-y local recurrence (LR) rates were 1.5% and 4%, respectively. The cumulative 5- and 10-y distant recurrence (DR) rates were 3% and 8%, respectively. The Cox regression revealed that HER2-positive/nonluminal subtypes had the highest risk of LR (P = 0.0025). The luminal B-like/HER2-positive subtypes had the highest risk of DR (P = 0.0019). HER2 positivity carried a higher risk of DR in women with luminal breast cancer who completed 5 y of adjuvant hormonal therapy (P = 0.02).

Conclusions: The IHC-defined subtype impacts on the prognosis of breast cancer ≤2 cm after BCS, determining significant differences in LR and DR rates. In the pre-"anti-HER2 therapy" era, patients with HER2-positive/nonluminal or luminal B-like/HER2-positive subtype had worse long-term outcomes than those with luminal A-like subtype.

Keywords: Breast; Cancer; Immunohistochemistry; Outcome; Phenotype.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Breast / pathology*
  • Breast / surgery
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism
  • Mastectomy, Segmental*
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / prevention & control
  • Prognosis
  • Prospective Studies
  • Radiotherapy, Adjuvant
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / analysis
  • Receptors, Progesterone / metabolism
  • Reoperation / statistics & numerical data
  • Retrospective Studies

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2