Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype

Abstract

Molecular subtyping confirms that breast cancer comprises at least four genetically distinct entities based on the expression of specific genes including estrogen receptor (ER), progesterone receptor (PR), and HER2/neu receptor. The quantitative influence of subtype on ipsilateral locoregional recurrence (LRR) is unknown. The aim of this study was to systematically appraise the influence of breast cancer subtype on LRR following breast conserving therapy (BCT) and mastectomy. A comprehensive search for studies examining outcomes after BCT and/or mastectomy according to breast cancer subtype was performed using Medline and cross-referencing available data. Reviews of each study were conducted and data extracted to perform meta-analysis. Primary outcome was LRR related to breast cancer subtype. A total of 12,592 breast cancer patients who underwent either BCT (n = 7,174) or mastectomy (n = 5,418) were identified from 15 studies. Patients with luminal subtype tumors (ER/PR +ve) had a lower risk of LRR than both triple-negative (RR 0.38; 95% CI 0.23-0.61); and HER2/neu-overexpressing (RR 0.34; 95% CI 0.26-0.45) tumors following BCT. Luminal tumors were also less likely to develop LRR than HER2/neu-overexpressing (OR 0.69; 95% CI 0.54-0.89) or triple-negative tumors (OR 0.61; 95% CI 0.46-0.79) after mastectomy. HER2/neu-overexpressing tumors have increased risk of LRR compared to triple-negative tumors (RR 1.44; 95% CI 1.06-1.95) following BCT but there was no difference in LRR between HER2/neu-overexpressing and triple-negative tumors following mastectomy (RR 0.91; 95% CI 0.68-1.22). Luminal tumors exhibit the lowest rates of LRR. Patients with triple-negative and HER2/neu-overexpressing breast tumors are at increased risk of developing LRR following BCT or mastectomy. Breast cancer subtype should be taken into account when considering local control and identifies those at increased risk of LRR, who may benefit from more aggressive local treatment.

Outcomes of Triple-Negative Versus Non-Triple-Negative Breast Cancers Managed with Breast-Conserving Therapy

“…Variable results were reported in other studies on TNBC managed with BCT (Nguyen et al, 2008;Freedman et al, 2009;Miller et al, 2009;Voduc et al, 2010). In a recent meta-analysis, Lowery et al (2012) included 12, 592 patients from 15 studies who either received BCT (n=7176) or mastectomy (n=5416). Around 15% (n=1865) patients had TNBC.…”

“…Gene expression profiling has shown that breast cancer is not a single disease but a spectrum of biological diversity (Lowery et al, 2012). Expression and identification of 496-gene has classified breast cancers into various subtypes.…”

Systematic review of the impact of breast‐conserving surgery on cancer outcomes of multiple ipsilateral breast cancers

“…A comprehensive IHC subtyping algorithm (six biomarkers) that can distinguish luminal B from luminal A cancers, and basal from triple‐negative disease, has potential clinical implications15 17, 18. Luminal cancers had a lower risk of 5‐year LRR than HER2‐positive or triple‐negative unifocal disease after BCS in 12 500 patients73. Ataseven and co‐workers22 reported increased associations between oestrogen receptor‐positive and HER2‐positive genotypes in MIBC, compared with unifocal cancers ( P < 0·001).…”

Impact of age, intrinsic subtype and local treatment on long-term local-regional recurrence and breast cancer mortality among low-risk breast cancer patients

“…Local failure has been associated with intrinsic subtype approximation in a meta-analysis by Lowery et al [18]; patients with LumA tumors were found to have a lower risk of local recurrence than patients with Basal/HER2 þ tumors. The studies included in the meta-analysis included mainly postmenopausal women and most studies included lymph node positive patients.…”