title: Pattern of Local Recurrence and Distant Metastasis in Breast Cancer By Molecular Subtype.
abstract: OBJECTIVE
  No longer considered a single disease entity, breast cancer is being classified into several distinct molecular subtypes based on gene expression profiling. These subtypes appear to carry prognostic implications and have the potential to be incorporated into treatment decisions. In this study, we evaluated patterns of local recurrence (LR), distant metastasis (DM), and association of survival with molecular subtype in breast cancer patients in the post-adjuvant radiotherapy setting.
  
  
  METHODS
  The medical records of 1,088 consecutive, non-metastatic breast cancer patients treated at a single institution between 2004 and 2012 were reviewed. Estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2) enrichment were evaluated by immunohistochemistry. Patients were categorized into one of four subtypes: luminal-A (LA; ER/PR+, HER2-, Grade 1-2), luminal-B (LB; ER/PR+, HER2-, Grade > 2), HER2 over-expression (HER2; ER/PR-, HER2+), and triple negative (TN; ER/PR-, HER2-).  Results: The median follow-up time was 6.9 years. During the follow-up, 16% (174/1,088) of patients failed initial treatment and developed either LR (48) or DM (126). The prevalence of LR was the highest in TN (12%) and the lowest in LA (2%). Breast or chest wall relapse was the most frequent site (≈80%) of recurrence in LA, LB, and HER2 subtypes, whereas the regional lymph nodes and chest wall were the common sites of relapse in the TN group (50.0%). DM rates were 6.4% in LA, 12.1% in LB, 19.2% in HER2, and 27.4% in TN subgroups. Five-year survival rates were 84%, 83%, 84%, and 77% in the LA, LB, HER2 and TN subgroups, respectively. There was a statistically significant association between survival and molecular subtypes in an univariate analysis. In the adjusted multivariate analysis, the following variables were independent prognostic factors for survival: T stage, N stage, and molecular subtype.
  
  
  CONCLUSIONS
  Of the four subtypes, the LA subtype tends to have the best prognosis, fairly high survival, and low recurrent or metastases rates. The TN and HER2 subtypes of breast cancer were associated with significantly poorer overall survival and prone to earlier recurrence and metastases. Our results demonstrate a significant association between molecular subtype and survival. The risk of death and relapse/metastases increases fewfold in TN compared to LA. Future prospective studies are warranted and could ultimately lead to the tailoring of adjuvant radiotherapy treatment fields based on both molecular subtype and the more conventional clinicopathologic characteristics.
authors.affiliation: Department of Radiation Oncology, KunMing Medical University Yunnan Provincial Cancer Hospital, Kunming, People's Republic of China.
authors.forename: Xingrao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Oncology, Division of Radiation Oncology, Segal Cancer Center-Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Baig
authors.affiliation: Department of Medicine and Pulmonary Oncology, Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Goulnar
authors.initials: G
authors.lastname: Kasymjanova
authors.affiliation: Department of Oncology, Division of Radiation Oncology, Segal Cancer Center-Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Kamran
authors.initials: K
authors.lastname: Kafi
authors.affiliation: Statistical Consultation Service Centre for Clinical Epidemiology, Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Holcroft
authors.affiliation: Department of Oncology, Division of Radiation Oncology, Segal Cancer Center-Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Hind
authors.initials: H
authors.lastname: Mekouar
authors.affiliation: Department of Oncology, Division of Radiation Oncology, Segal Cancer Center-Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Carbonneau
authors.affiliation: Department of Oncology, Division of Radiation Oncology, Segal Cancer Center-Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Boris
authors.initials: B
authors.lastname: Bahoric
authors.affiliation: Department of Oncology, Division of Radiation Oncology, Segal Cancer Center-Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Sultanem
authors.affiliation: Department of Oncology, Division of Radiation Oncology, Segal Cancer Center-Jewish General Hospital, McGill University, Montréal, Canada.
authors.forename: Thierry
authors.initials: T
authors.lastname: Muanza
keywords: breast cancer; molecular subtype; pattern; recurrence