Regional Recurrence Risk Following a Negative Sentinel Node Procedure Does Not Approximate the False-Negative Rate of the Sentinel Node Procedure in Breast Cancer Patients Not Receiving Radiotherapy or Systemic Treatment.

BACKGROUND: Although the false-negative rate of the sentinel lymph node biopsy (SLNB) in breast cancer patients is 5-7%, reported regional recurrence (RR) rates after negative SLNB are much lower. Adjuvant treatment modalities probably contribute to this discrepancy. This study assessed the 5-year RR risk after a negative SLNB in the subset of patients who underwent breast amputation without radiotherapy or any adjuvant treatment. METHODS: All patients operated for primary unilateral invasive breast cancer between 2005 and 2008 were identified in the Netherlands Cancer Registry. Patients with a negative SLNB who underwent breast amputation and who were not treated with axillary lymph node dissection, radiotherapy, or any adjuvant systemic treatment were selected. The cumulative 5-year RR rate was estimated by Kaplan-Meier analysis. RESULTS: A total of 13,452 patients were surgically treated for primary breast cancer and had a negative SLNB, and 2012 patients fulfilled the selection criteria. Thirty-eight RRs occurred during follow-up. Multifocal disease was associated with a higher risk of developing RR (P = 0.04). The median time to RR was 27 months and was significantly shorter in patients with estrogen receptor-negative (ER-) breast cancer (9.5 months; P = 0.003). The 5-year RR rate was 2.4% in the study population compared with 1.1% in the remainder of 11,440 SLNB-negative patients (P = 0.0002). CONCLUSIONS: Excluding the effect of radiotherapy and systemic treatment resulted in a twofold 5-year RR risk in breast cancer patients with a tumor-free SLNB. This 5-year RR rate was still much lower than the reported false-negative rate of the SLNB procedure.

Do patients whose tumor achieved a pathological response relapse at specific sites? A substudy of the EORTC 10994/BIG-1-00 trial.

PURPOSE: To determine the sites of first distant relapse in patients with or without pCR following neoadjuvant chemotherapy in breast cancer patients enrolled in the EORTC 10994/BIG-1-00 trial. METHODS: We included patients enrolled in the EORTC 10994/BIG-1-00 trial who received at least one chemotherapy cycle before surgery and who had been diagnosed with a distant relapse. pCR was defined as no evidence of residual invasive cancer in the primary tumor and axillary lymph nodes with or without residual ductal carcinoma in situ. Site of first distant relapse was categorized as 'soft tissue,' 'visceral,' 'skeletal,' 'central nervous system (CNS),' and 'other.' The association between relapse site and achievement of pCR was assessed using multivariate logistic regression models for molecular subtypes classification and preceding locoregional recurrence. RESULTS: The study included 383 (21%) eligible patients out of the 1856 randomized, of whom 28 (7%) had achieved pCR. Median follow-up was 5.4 years. Achievement of pCR was associated with a trend towards a decreased presentation of skeletal metastases [21% (pCR) vs. 50% (non-pCR), OR 0.32, adjusted p value = 0.071] and an increase in the proportion of patients with CNS metastases as first distant relapse site (21% vs. 9%, OR 2.39, adjusted p value = 0.183). Patients with pCR were more likely to present with only one relapse location category when compared to non-pCR (86% vs. 69%). CONCLUSION: Patients that achieved a pCR appeared less likely to present with skeletal metastases and more frequently presented with CNS metastases as first site of distant relapse, even after adjustment for molecular subtypes.

Prognostic Significance of Tumor-Positive Internal Mammary Sentinel Lymph Nodes in Breast Cancer: A Multicenter Cohort Study.

INTRODUCTION: The introduction of the sentinel lymph node biopsy (SLNB) in breast cancer has renewed interest in lymphatic drainage to the internal mammary (IM) nodes. The clinical impact of tumor positive IM nodes is not completely clear. This study evaluated the incidence and impact on overall survival of metastatic IM SLNs. METHODS: Between 1997 and 2010, 3685 patients underwent surgery including SLNB for primary breast cancer following an intratumoral or peritumoral radioactive-tracer injection. The presence of lymph node metastases was categorized according to the TNM-classification. Cumulative overall survival was estimated and the influence of metastases in the IM nodes and other factors was assessed by Cox-regression-analysis. RESULTS: In 754 patients (20.5 %) ipsilateral IM lymph nodes were visualized on preoperative lymphoscintigraphy, retrieval rate of IM SLNs was 81.0 %. IM metastases were detected in 130 patients (21.3 % of retrieved SLNs and 3.5 % of all patients respectively). The presence of IM metastases was associated with axillary metastases (p < 0.001). After a median follow-up of 61.2 months, 10.9 % of patients had died. In a multivariate analysis IM metastases did not have a significant effect on overall survival [HR] 1.20; CI: 0.73-1.98. In patients without axillary metastases (n = 2398), the presence of IM metastases (n = 43) was associated with worse survival [HR] 2.68; 95 % CI: 1.30-5.54. CONCLUSION: Overall, the presence of IM metastases did not effect overall survival independent of other prognostic factors including axillary metastases. However, the small subgroup of patients who had IM metastases alone had worse outcome than patients without any regional lymph node metastases.

Anti-angiogenic treatment in breast cancer: Facts, successes, failures and future perspectives.

Angiogenesis is one of the hallmarks of cancer and a crucial requisite in the development of tumors. Interrupting this process by blocking the vascular endothelial growth factor (VEGF) with the monoclonal antibody bevacizumab has been considered a possible breakthrough in the treatment of various types of cancer, especially for advanced disease. However in breast cancer, studies have shown ambivalent results causing debate about the value of this drug. In this article, we review the evidence for anti-angiogenic treatment options for breast cancer, as well as discuss the possible factors limiting the effectiveness of anti-angiogenic agents and offer a recommendation regarding the future research on these therapies for the treatment of breast cancer.

Contemporary Locoregional Recurrence Rates in Young Patients With Early-Stage Breast Cancer.

PURPOSE: The aim of this study was to evaluate contemporary rates of local recurrence (LR) and regional recurrence (RR) in young patients with breast cancer in relation to tumor biology as expressed by biomarker subtypes. PATIENTS AND METHODS: Women < 35 years of age who underwent surgery for primary unilateral invasive breast cancer between 2003 and 2008 were selected from the Netherlands Cancer Registry. Patients were categorized according to biomarker subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year risks of developing LR and regional lymph node recurrence were estimated by using Kaplan-Meier statistics. RESULTS: A total of 1,000 patients were identified, of whom 59% had a known subtype: 39% HR-positive/HER2-negative; 17% HR-positive/HER2-positive; 10% HR-negative/HER2-positive; and 34% HR-negative/HER2-negative (triple negative). Overall 5-year LR and RR rates were 3.5% and 3.7%, respectively. A decreasing trend for both rates was observed over time and was accompanied by a significant decrease in the risk of distant metastases (DM). LR occurred in 4.2%, RR in 6.1%, and DM in 17.8% of patients in 2003, and in 3.2%, 4.4%, and 10.0%, respectively, in 2008. LR and RR rates varied with biomarker subtype. These differences were borderline significant when analyzed for the entire study period (P = .056 and P = .014, respectively) and leveled off after the introduction of trastuzumab after 2005 (P = .24 and P = .42, respectively). Patients with lymph node metastases at the time of diagnosis had an increased risk of RR. The type of surgery performed-breast-conserving or mastectomy-did not influence rates of LR and RR. CONCLUSION: Overall, the rates of LR and RR in young patients with early-stage breast cancer were relatively low and varied by biomarker subtype.