Purpose: To assess the overall survival (OS) of early human epidermal growth factor receptor 2 (HER2)-enriched breast cancer patients after receiving neoadjuvant trastuzumab (NAT) compared to adjuvant trastuzumab (AT) treatment and the difference in local-regional relapse (LRR) rate with this tumor and treatment between women after mastectomy and women after breast-conserving therapy (BCT).
Methods: Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. A pooled odds ratio (OR) with a 95% confidential interval (CI) was calculated. The StataSE version 12.0 software was employed for meta-analysis.
Results: Twelve available clinical studies containing 2366 subjects were included. The OS of NAT compared with that of AT was not significantly different (pooled OR=1.04; 95% CI, 0.47–2.33). There was a significantly lower LRR rate for patients with mastectomy compared to those with BCT (pooled OR=0.58; 95% CI, 0.38–0.89); however, subgroup analysis revealed that the significant advantage of LRR for mastectomy compared to BCT was only represented in women without trastuzumab treatment (pooled OR=0.52; 95% CI, 0.31–0.88) compared to those who received trastuzumab treatment (pooled OR=0.71; 95% CI, 0.34–1.49).
Conclusion: Early stage HER2-overexpression breast cancer patients benefit with an equivalent OS from NAT treatment compared to AT. Patients who underwent mastectomy and BCT experienced a similar LRR rate if they received anti-HER2 targeted therapy of trastuzumab, but the LRR rate was discernibly reduced in patients who received mastectomy compared to BCT if they did not also receive trastuzumab treatment.
Keywords: human epidermal growth factor receptor 2, trastuzumab, mastectomy, breast conserving therapy, breast cancer
Neoadjuvant systematic chemotherapy in breast cancer is a preoperative treatment, which is initially applied locally to advanced tumors to downgrade primary tumor and regional lymph nodes and enable their removal by operation. Currently, neoadjuvant chemotherapy is widely used in early resectable disease, mainly to allow breast-conserving therapy (BCT).1–3 Adjuvant chemotherapy is postoperative and attenuates breast cancer mortality by at least 15%.4 Many randomized clinical trials and meta-analyses confirm the equivalent overall survival (OS) of breast cancer women after receiving preoperative chemotherapy compared to those who undergo postoperative chemotherapy;5–9 however, these studies are imperfect, as they all failed to perform the subgroup analysis on different molecular subtypes of breast cancer.
In the period before 1980, the modified radical mastectomy was the standard surgical method for breast cancer. In the early 1980s, two published randomized trials reformed this standard modality and confirmed that the survival benefits from BCT were equivalent to those of mastectomy.10,11 The Early Breast Cancer Trialists’ Collaborative Group carried out a large-scale meta-analysis that further pooled the results from both randomized trials, finding the equality of OS and disease-free survival (DFS) between mastectomy and BCT.12 Currently, instead of mastectomy, BCT has become the appropriate and preferred treatment for most early stage breast cancer patients,13 and it prevents the physical and psychological burden of sacrificing breast on women as much as possible.14
Human epidermal growth factor receptor 2 (HER2)-overexpression breast cancer accounts for approximately 15–25% of the primary breast tumors.15 Trastuzumab is currently indispensable for treating HER2-positive breast cancer. Prior to treatment with the anti-HER2 targeted drug, the local-regional recurrence (LRR) of this cancer molecular subtype is significantly greater than that of other phenotypes of disease, specifically Luminal A.16 Voduc et al16 found that the LRR rate of HER2-enriched breast cancer patients without trastuzumab treatment who underwent BCT and those who received trastuzumab was 21% and 17% at 10 years, respectively. After receiving trastuzumab, there is discernible reduction in the high LRR rate of HER2-positive breast tumors; a study from Debled et al17 showed that those women treated with BCT or mastectomy had a significantly reduced 4-year LRR rate of 2.9% or 0%, respectively. However, the LRR rates between these two surgical strategies in treating HER2-amplified breast carcinoma were not compared in these studies. Therefore, the aim of our article was to separately pool all clinical studies that concomitantly documented the OS outcomes of early HER2-overexpression breast cancer patients who received neoadjuvant trastuzumab (NAT) and adjuvant trastuzumab (AT) and that concurrently described the LRR rate of those women undergoing mastectomy and BCT. We aimed to identify the more applicable and preferably primary treatment strategy for this subtype of breast tumor. We included women treated with NAT or mastectomy as the study cohort and those with AT or BCT treatment as the control cohort.
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