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Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype
Aoife J Lowery1, Malcolm R Kell, Ronan W Glynn
1Surgery, School of Medicine, National University of Ireland, Galway, Ireland.
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.
Insights
Breast cancer subtypes significantly impact locoregional recurrence (LRR) risk after treatment. Luminal tumors show the lowest LRR, while triple-negative and HER2-overexpressing types have higher risks, especially after breast conserving therapy.
Area of Science:
- Oncology
- Genetics
- Surgical Oncology
Background:
- Breast cancer is molecularly diverse, with subtypes defined by gene expression (ER, PR, HER2/neu).
- The impact of these subtypes on locoregional recurrence (LRR) after breast cancer treatment remains unclear.
Purpose of the Study:
- To systematically evaluate how breast cancer molecular subtypes influence LRR risk following breast conserving therapy (BCT) and mastectomy.
- To identify subtypes with elevated LRR risk for personalized treatment strategies.
Main Methods:
- A meta-analysis was performed on 15 studies encompassing 12,592 patients treated with BCT or mastectomy.
- Data on LRR were extracted and analyzed based on breast cancer subtype (luminal, triple-negative, HER2-overexpressing).
Main Results:
- Luminal tumors (ER/PR+) demonstrated the lowest LRR risk across both BCT and mastectomy.
- Triple-negative and HER2-overexpressing tumors showed significantly higher LRR risk compared to luminal tumors.
- HER2-overexpressing tumors had a higher LRR risk than triple-negative tumors after BCT, but not after mastectomy.
Conclusions:
- Breast cancer subtype is a critical factor in predicting LRR after local therapy.
- Patients with triple-negative and HER2-overexpressing subtypes require consideration for more intensive local treatment to mitigate LRR.
- Subtyping is essential for tailoring treatment and improving local control in breast cancer management.