Association between background parenchymal enhancement and tumor response in patients with breast cancer receiving neoadjuvant chemotherapy

PurposeTo analyze the relationships between background parenchymal enhancement (BPE) of the contralateral healthy breast and tumor response after neoadjuvant chemotherapy (NAC) in women with breast cancer.Materials and methodsA total of 228 women (mean age, 47.6 years ± 10 [SD]; range: 24–74 years) with invasive breast cancer who underwent NAC were included. All patients underwent breast magnetic resonance imaging (MRI) before and after NAC and 127 patients underwent MRI before, during (after the 4th cycle of NAC) and after NAC. Quantitative semi-automated analysis of BPE of the contralateral healthy breast was performed. Enhancement level on baseline MRI (baseline BPE) and MRI after chemotherapy (final BPE), change in enhancement rate between baseline MRI and final MRI (total BPE change) and between baseline MRI and midline MRI (early BPE change) were recorded. Associations between BPE and tumor response, menopausal status, tumor phenotype, NAC type and tumor stage at diagnosis were searched for. Pathologic complete response (pCR) was defined as the absence of residual invasive cancer cells in the breast and ipsilateral lymph nodes.ResultsNo differences were found in baseline BPE, final BPE, early and total BPE changes between pCR and non-pCR groups. Early BPE change was higher in non-pCR group in patients with stages 3 and 4 breast cancers (P = 0.019) and in human epidermal growth factor receptor 2 (HER2)-negative patients (P = 0.020).ConclusionEarly reduction of BPE in the contralateral breast during NAC may be an early predictor of loss of tumor response, showing potential as an imaging biomarker of treatment response, especially in women with stages 3 or 4 breast cancers and in HER2 – negative breast cancers.     

Outcome of radiotherapy for clinically overt metastasis to the internal mammary lymph node in patients receiving neoadjuvant chemotherapy and breast cancer surgery

PurposeThis study was aimed to assess the outcome of radiotherapy and determine prognostic factors for survival in breast cancer patients with clinically overt metastasis to the internal mammary lymph node (IMN+).MethodsWe retrospectively reviewed the medical records of 193 patients with IMN + breast cancer who received neoadjuvant chemotherapy (NAC), breast surgery without internal mammary lymph node (IMN) dissection, and postoperative radiotherapy at 9 hospitals between 2009 and 2013. Breast-conserving surgery or mastectomy was performed after taxane-based NAC. Radiotherapy was administered to the whole breast/chest wall and regional nodes. IMN-covering radiotherapy was performed in 92.2% of patients with median dose of 58.4 Gy (range, 44.9–69.1 Gy). The overall survival (OS), disease-free survival (DFS), and IMN failure-free survival (IMNFFS) were analyzed.ResultsAfter median follow-up of 71 months, 9 patients (4.7%) developed IMN failure and simultaneous distant metastasis. The 5-year DFS, OS, and IMNFFS was 68.6%, 81.8%, and 95.3%, respectively. Non-triple-negative breast cancer, Ki-67 ≤ 10%, pathological complete response (CR) in tumor and axillary node, and radiologic CR of IMN after NAC were significant factors for predicting higher DFS; however, IMN radiation dose was not significant determinants for DFS. The 5-year DFS of patients with IMN-dose ≤ 50.0 Gy and those with >50.0 Gy was 86.7% and 76.7%, respectively (p = 0.41).ConclusionsA multimodality strategy including NAC, breast surgery, and IMN-covering radiotherapy was effective for patients with overt IMN + breast cancer. Even without an IMN dissection, most patients were IMN failure-free with an IMN-focusing radiotherapy.     

Is [18F] fluorodeoxyglucose uptake by the primary tumor a prognostic factor in breast cancer?

BackgroundWe retrospectively investigated ¹⁸F-FDG uptake by the primary breast tumor as a predictor for relapse and survival.Patients and methodsWe studied 203 patients with cT1-T3N0 breast cancer. Standardized uptake value (SUVmax), was measured on the primary tumor. After a median follow-up of 68 months (range 22–80), the relation between SUVmax and tumor factors, disease free-survival (DFS) and overall survival (OS) was investigated.ResultsIn the PET-positive patients, the median FDG uptake by the tumor was 4.7. FDG uptake was significantly related to tumor size, number of involved axillary nodes, grade, negative ER, high Ki-67 and HER2 overexpression. No distant metastases or deaths occurred in the PET-negative group. Five-year DFS was 97% and 83%, respectively in the PET-negative and PET-positive groups (P = 0.096). At univariate analysis, DFS was significantly lower in patients with SUVmax >4.7 compared to the patients with negative PET (P = 0.042), but not to the patients with SUVmax ≤4.7 (P = 0.106). At multivariable analysis, among PET-positive patients, SUVmax was not an independent prognostic factor for DFS (HR_{>4.7 vs ≤4.7}: 1.02 (95% CI 0.45–2.31)). Five-year OS was 100% and 93%, respectively, in the PET-negative and PET-positive groups (P = 0.126).ConclusionFDG uptake by the primary lesion was significantly associated with several prognostic variables, but it was not an independent prognostic factor.     

Influence of age as a continuous variable on the prognosis of patients with pT1-2N1 breast cancer

PurposeTo assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT).MethodsWe retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes.ResultsThe median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association <0.05; P-linear association >0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204–0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P < 0.05). In patients >50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS.ConclusionsAge was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.     

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy

BackgroundIt is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.MethodsWe analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.ResultsAfter a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018).ConclusionsIMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.     

The prognostic significance of metaplastic carcinoma of the breast (MCB) – A case controlled comparison study with infiltrating ductal carcinoma

PurposeMetaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast cancer with an incidence of less than 0.1%–0.5%. Due to its rarity, the clinical characteristics and prognostic significance of MCB compared with other common breast cancers (like infiltrating ductal carcinoma [IDC], and infiltrating lobular carcinoma [ILC]) are not clear, and controversial among different reports.MethodsWe performed a collective comparison study of multi-institutional cases to evaluate the clinical characteristics and prognostic status of MCB to compare with IDC and ILC. A case control analysis was performed to minimize the bias from clinicopathologic factors between IDC and MCB. Disease free survival (DFS) and overall survival (OS) between groups were compared.ResultsForty-five MCB patients were enrolled from the 4 medical centers and compared with 1777 IDC and 53 ILC patients from the CCH cancer registry database comprise the current study. Compared with IDC, MCB was associated with older age, larger tumor size, a lesser lymph node positive rate, a higher likelihood of distant metastasis, higher tumor grade, lower ER-positive tumor, and higher triple negative breast cancer subtype (TNBC). MCB was associated with worse OS (p = 0.031) than IDC, but no difference in DFS (p = 0.071); however, MCB was not statistically different from ILC in both DFS and OS (p = 0.289 and 0.132, respectively). Compared with the case-controlled IDC group, MCB patients had poorer OS (p = 0.040), but no difference in DFS (p = 0.439).ConclusionMCB is associated with poorer OS than IDC, and this was related to tumor behavior rather than clinicopathologic factors.     

Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer

Background  We sought to determine the significance of Ki-67, one of the tumor cell proliferation markers, as a useful prognostic factor in early breast cancer. Methods  A total of 1080 consecutive patients with stage I or II breast cancer that underwent surgery between 1998 and 2003 were enrolled. Patients were categorized on the basis of the 2007 St. Gallen consensus and Adjuvant! Online. The expression of Ki-67 in the tumor was assayed by immunohistochemistry (cutoff value, 10%). Results  Univariate analysis determined that tumor size, lymph node involvement, histologic grade, estrogen receptor, progesterone receptor, bcl-2, and Ki-67 (≥10%) were statistically significant for both overall survival (OS) and distant metastasis-free survival (DFS). Of these factors, lymph node involvement and high Ki-67 expression were identified as independent prognostic factors for OS and DFS on the basis of multivariate analysis. The survivals of intermediate- and high-risk groups according to 2007 St. Gallen consensus were further separated by Ki-67 expression level (5-year DFS rate = 91.9% vs. 86.3% for Ki-67 < 10% and ≥10%, respectively in intermediate-risk group (P = .01); 5-year DFS rate = 82.5% vs. 61.4% for Ki-67 < 10% and ≥10%, respectively in high-risk group (P = .01)). The survivals of low- and high-risk groups according to Adjuvant! Online were further separated by Ki-67 expression level (5-year DFS rate = 97.8% vs. 89.5% for Ki-67 < 10% and ≥10%, respectively in low-risk group (P = .02); 5-year DFS rate = 9.4% vs. 82.6% for Ki-67 < 10% and ≥10% in high-risk group (P = .005)). Conclusions  Ki-67 is an independent prognostic factor for DFS and OS in early breast cancer and can provide additional prognostic information on the risk stratification with the use of the 2007 St. Gallen consensus and Adjuvant! Online. S.-Y. Jung and W. Han contributed equally to this work.     

Outcomes Following Liver Transplantation for Metastatic Neuroendocrine Tumors

Introduction

Metastatic disease is generally considered as an absolute contraindication for liver transplantation. However, due to relatively low aggressiveness and slow progression rates, liver metastases from neuroendocrine tumors (NETs) form an exception to this rule. Given the scarcity of available data, the purpose of this study was to evaluate long-term outcomes following liver transplantation for NET metastases.

Material and Methods

There were 12 primary liver transplantations in patients with NET metastases out of 1334 liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw) in the period between December 1989 and October 2013. Overall survival (OS) and disease-free survival (DFS) were set as primary and secondary outcome measures, respectively.

Results

Median follow-up was 7.9 years. For all patients, OS rate was 78.6% at 10 years and DFS rate was 15.5% at 9 years. Intraoperative transfusions of packed red blood cells (P = .021), Ki-67 proliferative index more than 2% (P = .048), and grade 2 tumors (P = .037) were identified as factors significantly associated with worse DFS. Notably, loss of E-cadherin expression (P = .444), mitotic rate (P = .771), extent of liver involvement (P = .548), primary tumor site (P = .983), and recipient age (P = .425) were not significantly associated with DFS.

Conclusions

Excellent long-term OS rates support liver transplantation for unresectable NET metastases despite almost universal post-transplantation tumor recurrence. Selection of patients with G1 tumors with Ki-67 index not exceeding 2% and reducing the requirement for intraoperative blood transfusions might improve DFS rates.     

Dual-phase FDG PET/CT for predicting prognosis in operable breast cancer

PurposeWe aimed to investigate the role of dual-phase FDG PET/CT in predicting the prognosis of patients with operable breast cancer.MethodsWe retrospectively reviewed the data of 998 patients who underwent radical treatment for breast cancer. Before treatment, PET/CT scans were performed 1 and 2 h after FDG administration. The maximum standardized uptake value (SUVmax) at both time points (SUVmax1 and SUVmax2) in the primary tumor and the retention index (RI) were calculated. PET recurrence risk (PET-RR) was determined based on the SUVmax1 and RI, and disease-free survival (DFS) and overall survival (OS) were evaluated according to the metabolic parameters. Propensity score matching was performed to adjust for biological characteristics.ResultsThe cut-off values for SUVmax1 and RI were 3 and 5%, respectively. The 5-year DFS was 94.9% and 86.1% (P < 0.001), and the 5-year OS was 97.6% and 92.7% (P < 0.001) in the low and high PET-RR groups, respectively. In multivariate analysis, high T status, nodal metastasis, the triple-negative subtype, and high PET-RR were independent factors of poor DFS. Propensity score matching revealed similar findings (5-year DFS 91.8% vs. 88.6%, P = 0.041 and 5-year OS 97.1% vs. 94.2%, P = 0.240, respectively).ConclusionThe combined parameters of SUVmax1 and RI on dual-phase FDG PET/CT were useful for predicting prognosis of patients with breast cancer. Patients with a high SUVmax1 and a negative time course of FDG uptake had a favorable prognosis.     

Benefits of neoadjuvant therapy compared with adjuvant chemotherapy for the survival of patients with HER2-positive breast cancer: A retrospective cohort study at FUSCC

PurposeNeoadjuvant therapy (NAT) is considered the standard of care for patients with HER2-positive breast cancer (BC). However, there is no proven survival benefit of NAT compared to adjuvant therapy for the survival of patients with early-stage HER2-positive BC. This study aimed to compare the prognosis of HER2-positive BC patients treated with NAT to that of patients treated with adjuvant therapy.MethodsThis was a single-center real-world retrospective study. This study analyzed the disease-free survival (DFS) and overall survival (OS) of 538 HER2-positive BC patients treated with neoadjuvant therapy and 2684 patients treated with adjuvant therapy at Fudan University Shanghai Cancer Center (FUSCC) between 2012 and 2016. Patients with a clinical tumor size (cT) ≤5 cm or >5 cm were matched using the propensity score matching (PSM) method to prevent selection bias.ResultsAfter PSM, among patients with cT ≤ 5 cm, there was no significant difference in DFS (P = 0.08) or OS (P = 0.11) between the two groups. The analysis of survival outcomes of patients treated with neoadjuvant and adjuvant therapy in the different chemotherapy subgroups yielded consistent results. According to multivariate analysis, lymph node status and response to NAT showed independent prognostic value for OS and DFS. Among patients with cT > 5 cm, the DFS (P = 0.25) and OS (P = 0.57) of patients treated with NAT were similar to those of patients treated with adjuvant therapy after PSM.ConclusionWe confirmed the equivalent effects of adjuvant therapy and NAT in HER2-positive BC patients. Neoadjuvant therapy should be used for patients with HER2-positive BC.     

Serum levels of CEA and CA15-3 in different molecular subtypes and prognostic value in Chinese breast cancer

The prognostic significance of preoperative carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels in breast cancer is controversial. This study evaluated the prognostic value of preoperative serum CEA and CA15-3 levels in Chinese breast cancer patients. A total of 470 patients with breast cancer had preoperative CEA and CA15-3 concentrations measured. The relationships between preoperative concentration and clinicopathological factors and outcomes were determined. CEA and CA15-3 levels were increased in 34 (7.2%) and 58 (12.3%) patients, respectively. Elevations of serum CEA and CA-15-3 levels correlated with the primary tumor size and axillary lymph node status. CEA levels were lower in patients with triple-negative breast cancer than in those with other subtypes (P = 0.002). The 5-year distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) of CEA-negative vs. CEA-positive patients were 84.1% vs. 54.5% (P < 0.001), 82.7% vs. 54.8% (P < 0.001), and 89.7% vs. 78.5% (P = 0.007), respectively. The 5-year DMFS, DFS, and OS of CA15-3-negative vs. CA15-3-positive patients were 84.0% vs. 69.6% (P = 0.002), 83.0% vs. 66.2% (P < 0.001), 90.9% vs. 74.2% (P = 0.005), respectively. Multivariate analysis of prognosis indicated that CEA and CA15-3 levels were independent prognostic factors for DMFS (P = 0.021) and DFS (P = 0.032), and DFS (P = 0.014) and OS (P = 0.032), respectively. Serum levels of CEA and CA15-3 may differ in breast cancer molecular subtypes and preoperative levels of CEA and CA15-3 have a significant effect on prognosis in Chinese women with breast cancer.     

Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

PurposeTo assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival.MethodsPreoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355).ResultsCPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS.ConclusionCPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.     

Clinical Significance of Axillary Microresiduals After Neoadjuvant Chemotherapy in Breast Cancer Patients with Cytologically Proven Metastases

Background  Neoadjuvant chemotherapy (NAC) has been widely accepted for advanced breast cancer patients, and pathological complete remission (pCR) was revealed to be an important prognostic factor. The pCR status of cytologically proven axillary metastases (ALN-pCR) offers a more powerful prognostic predictor than pCR of the main tumor. This study evaluated the clinical significance of residual micrometastases and discusses screening methods after NAC in patients with cytologically proven axillary metastases. Methods  Eighty patients with a diagnosis of cytologically proven axillary metastases received NAC. All dissected lymph nodes were evaluated using multislice sectioning and cytokeratin immunohistochemistry, and categorized into four groups: no metastases (ALN-pCR), and with metastases ≤0.2 mm (ALN-itc), >0.2 mm but ≤2 mm (ALN-mic), and >2 mm (ALN-mac). Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan–Meier method based on the status of residual metastases. Results  DFS in patients with ALN-pCR and ALN-itc was significantly longer than that with ALN-mic (P = 0.007, P = 0.045, respectively). OS with ALN-pCR was significantly longer than that with ALN-mic (P = 0.004). There was no significant difference in DFS or OS between ALN-mac and ALN-mic. These data showed the clinical significance of microresidual metastases >0.2 mm after NAC in patients with cytologically proven axillary metastases. Conclusions  Using multislice sectioning, screening for ALN-mic after NAC was clinically important, and that for ALN-itc was not clinically essential.     

Different prognostic significance of CD24 and CD44 expression in breast cancer according to hormone receptor status

Objective

CD44⁺CD24^−/low-expressing tumor cells have been studied as tumorigenic stem cells in vitro study. This study was designed to determine the clinical implication of the CD44 and CD24 expression in breast cancer.

Methods

Tissue microarray blocks containing 643 consecutive cases of invasive breast carcinomas from 1993 to 1998 were immunostained for CD44 and CD24. The median follow-up period was 127 months.

Results

CD44⁻CD24⁺ phenotype was associated with frequent hormone receptor positivity and Her2/neu positivity (P = 0.000; Both). The CD44⁺CD24⁻ phenotype was inversely associated with lymph node metastasis (P = 0.002), and it showed positive associations with prolonged disease-free survival (DFS; P = 0.003) and overall survival (OS; P = 0.002). 10-year DFS and OS were 68.9% and 74.6% for CD24 negative group, 55.6% and 60.9% for CD24 positive group (P = 0.001; Both). 10-year DFS and OS were 62.2% and 68.1% for CD44 negative group, 73% and 77.7% for CD44 positive group (P = 0.012, P = 0.013, respectively). In a multivariate analysis, CD24 expression was negatively related to OS only in the receptor positive group (Hazard ratio = 2.03; P = 0.003; 95% CI: 1.27-3.24) and CD44 expression was positively related to OS only in the hormone receptor negative group (hazard ratio = 0.58; P = 0.022; 95% CI: 0.36-0.92).

Conclusions

The CD44⁺CD24⁻ group is considered a favorable prognostic subgroup in breast cancer. CD24 expression was a poor prognosis marker in hormone receptor positive breast cancer, and CD44 expression was a good prognostic marker in the receptor negative group.     

Immunohistochemical prediction of brain metastases in patients with advanced breast cancer: The role of Rad51

BackgroundThere are no clinically useful biomarkers predictive of brain metastases (BM) in breast cancer. In this study, we investigated the correlation between expression of selected proteins in the primary tumor and the risk of BM in patients with metastatic breast cancer (MBC).MethodsThe study included 198 MBC patients (96 with and 102 without BM). Using tissue microarrays derived from the primary tumor, we assessed by immunohistochemical expression of ER, PR, HER2, Ki-67, CK5/6, EGFR, HER3, CXCR4, Rad51, E-cadherin, and claudin 3 and 4.ResultsKi-67 ≥14% (hazard ratio [HR] 2.76; P < 0.001), cytoplasmic expression of Rad51 (HR 1.87; P = 0.014) and ER-negativity (HR 1.72; P = 0.029) were associated with increased risk of BM in the multivariate analysis. A three-biomarker profile including ER, Ki-67 and Rad51 vs. other subtypes combined yielded an HR of 4.43 (P < 0.001).ConclusionsER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.     

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience

IntroductionIt remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM.MethodA retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed.ResultsA total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications’ rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively.ConclusionBased on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection.     

Prognostic value of FOXA1 in breast cancer: A systematic review and meta-analysis

BackgroundDespite some published papers analyzing the prognostic role of forkhead-box A1 (FOXA1) in breast cancer, it has not yet been considered as an established prognostic factor in clinical practice. The present meta-analysis evaluated the prognostic value of FOXA1 in breast cancer.MethodsPubMed, Web of Science and Embase databases were searched for relevant published literature that evaluated the correlation between FOXA1 and breast cancer. Either a fixed or random effect model was applied to estimate the pooled hazard ratio (HR) for FOXA1 prognosis in breast cancer.ResultA total of nine articles comprising 6386 breast cancer patients met the inclusion criteria. Among these nine studies, five studies and four studies investigated the prognostic association with disease-free survival (DFS), and overall survival (OS), respectively. Meta-analysis results suggested that high FOXA1 expression was positively associated with DFS (pooled HR: 0.43, 95% CI: 0.23–0.81; P < 0.05) and OS (pooled HR: 0.39, 95% CI: 0.26–0.60; P < 0.05) in breast cancer patients. No publication bias was discovered by Begg's test in this meta-analysis.ConclusionThe results from this meta-analysis indicated that elevated FOXA1 expression level was associated with better outcome in breast cancer.     

Clinical impact of adjuvant radiation therapy delay after neoadjuvant chemotherapy in locally advanced breast cancer

Backgroundand Purpose: Post-operative radiation therapy (PORT) is usually indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy (NAC) and surgery. However, the optimal timing to initiation of PORT is currently unknown.Material and methodsWe retrospectively evaluated data from patients with BC who received PORT after NAC and surgery at our institution from 2008 to 2014. Patients were categorized into three groups according to the time between surgery and PORT: <8 weeks, 8–16 weeks and >16 weeks.ResultsA total of 581 patients were included; 74% had clinical stage III. Forty-three patients started PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks after surgery was associated with better disease-free survival (DFS) (<8 weeks versus 8–16 weeks: HR 0.33; 95% CI 0.13–0.81; p = 0.02; <8 weeks versus >16 weeks: HR 0.38; 95% CI 0.15–0.96; p = 0.04) and better overall survival (OS) (<8 weeks versus 8–16 weeks: HR 0.22; 95% CI 0.05–0.90; p = 0.036; <8 weeks versus >16 weeks: HR 0.28; 95% CI 0.07–1.15; p = 0.08).ConclusionPORT started up to 8 weeks after surgery was associated with better DFS and OS in locally-advanced BC patients submitted to NAC. Our findings suggest that early initiation of PORT is critically important for these patients. However, the low numbers of patients and events in this study prevent us from drawing firm conclusions.     

Mammographic density and prognosis in primary breast cancer patients

PurposeMammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients.MethodsA total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status.ResultsAfter median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect.ConclusionsAlthough MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC.