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Background: The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients > 50 years with RS > 25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS.Methods: We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged > 50 years. The primary outcome was high-risk RS (> 25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method, and externally validated in another cohort. We then assessed the nomogram in different subgroups of patients and compared it with several published models.Results: A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772-0.825) and optimism adjusted AUC was 0.794 (95% CI 0.781-0.822). External validation demonstrated an AUC value of 0.746 (95% CI 0.685-0.807), which had no significant difference with the training cohort (P = 0.124). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes in both internal and external validation. The nomogram had better discriminate ability in patients who had tumors > 2 cm (AUC = 0.847, 95% CI 0.804-0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al. CONCLUSIONS: We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing. [ABSTRACT FROM AUTHOR]

Background: Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented.Methods: Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive.Results: There were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (κ = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB.Conclusion: CNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors. [ABSTRACT FROM AUTHOR]

Background: Triple negative breast cancer (TNBC) occurs in approximately 10% to 25% of all patients with breast cancer and is associated with poor prognosis. Neo-adjuvant chemotherapy has been reported to produce a higher pathologic complete response (pCR) rate in TNBC. If pCR is achieved, patients with TNBC had a similar survival with non-TNBC patients. The aim of our study was to investigate the protein expression of epithelial growth factor receptor (EGFR) and response to neo-adjuvant chemotherapy and clinical outcome in patients with TNBC compared with non-TNBC.Methods: A total of 198 locally advanced breast cancer patients who received neo-adjuvant chemotherapy were studied. Immunohistochemistry (IHC) was carried out to detect the protein expression of EGFR in tumor samples. Clinical and pathological parameters, pCR rate and survival data were compared between 40 TNBCs and 158 non-TNBCs.Results: In 198 cases who received neo-adjuvant chemotherapy, significant differences exist in surgical therapy (P=0.005) and pCR rate (P=0.012) between patients with TNBCs and non-TNBCs. Overexpression of EGFR was significantly associated with pCR rate in patients with TNBCs (P < 0.001). Survival analysis revealed that patients with TNBCs had worse DFS and OS than those with non-TNBCs (P = 0.001, P < 0.001 respectively). Furthermore, for patients with non-TNBCs, those who achieved pCR had better DFS and OS than those who achieved RD (both P < 0.001).Conclusions: Our results suggested that patients with TNBCs had increased pCR rates compared with non-TNBC. Overexpression of EGFR predicted better response to neo-adjuvant chemotherapy in patients with TNBCs. [ABSTRACT FROM AUTHOR]

Background: To investigate the accuracy of core needle biopsy (CNB) in evaluating breast cancer estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 status and to identify factors which might be associated with Ki67 value change after CNB., Methods: A retrospective study was carried out on 276 patients with paired CNB and surgically removed samples (SRS). Clinico-pathological factors as well as the surgery time interval (STI) between CNB and surgery were analyzed to determine whether there were factors associated with Ki67 value change after CNB. Five tumor subtypes were classified as follows: Luminal A, Luminal B-HER2-, Luminal B-HER2+, Triple Negative (TN), and HER2+. Ki67 value change was calculated as SRS minus CNB., Results: Mean STI after CNB was 4.5 (1-37) days. Good agreement was achieved for ER, PR, and HER2 evaluation between CNB and SRS. However, Ki67 expression level was significantly higher in SRS compared with CNB samples: 29.1 % vs. 26.2 % (P < 0.001). Both univariate and multivariate analysis demonstrated that STI and molecular subtype were associated with a Ki67 change after CNB. Luminal A tumors experienced more Ki67 elevation than Luminal B-HER2- diseases (6.2 % vs -0.1 %, P = 0.014). Patients with longer STI after CNB had a higher Ki67 increase: -1.1 % within 1-2 days, 2.1 % with 3-4 days, and 5.6 % more than 4 days, respectively (P = 0.007). For TN and HER2+ tumors, the Ki67 change was apt to be 0 with STI ≤ 4 days, while a >7 % Ki67 increase was noticed in patients with STI ≥ 5 days., Conclusion: CNB was accurate in evaluating ER, PR, HER2, and molecular subtype status. Ki67 value significantly increased after CNB, which was associated with STI and molecular subtype. Further translational research needs to consider Ki67 changes following CNB among different breast cancer molecular subtypes.

Background: This study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC)., Methods: One-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67)., Results: Patients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p = 0.034, p = 0.027, respectively). A significantly increased risk of death was associated with lack of pre-ER expression (p = 0.002). Among patients with non-pCR, those with a pathological response at the tumor site with special involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk of disease relapse and death (p < 0.001, p = 0.001, respectively)., Conclusion: This study suggests the promising use of a VE regimen as NC for Chinese NLABC after a median follow-up of 63.4 months. Pathological response in the tumor site, pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important variables that predicted long-term outcome. Patients with pathological special involvement at the primary site after NC had the lowest survival rates.