Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study.

PURPOSE: Alongside the modern trend of delaying childbirth, the high incidence of breast cancer among young women is causing significant pregnancy-related problems in Korea. We estimated the incidence of childbirth for young Korean breast cancer survivors compared with women who did not have breast cancer using a nationally representative dataset. METHODS: Using a database from the National Health Insurance Service in South Korea, we analyzed 109,680 women who were between 20 and 40 years old between 2007 and 2013. They were prospectively followed, and childbirth events were recorded until December 31, 2015. We compared childbirth rates and characteristics between the breast cancer survivors and the noncancer controls. RESULTS: Compared to 10,164 childbirths among 91,400 women without breast cancer (incidence rate: 22.3/1000), 855 childbirths occurred among 18,280 breast cancer survivors (incidence rate: 9.4/1000); the adjusted hazard ratio (HR) for childbirth was 0.41 (95% CI 0.38-0.44). Chemotherapy, endocrine therapy, and target therapy were associated with the decreasing childbirths among survivors, with corresponding adjusted HRs of 0.61 (0.53-0.70), 0.44 (0.38-0.51), and 0.62 (0.45-0.86), respectively. Breast cancer survivors had a lower probability of full-term delivery and a higher frequency of preterm labor than controls, with corresponding adjusted ORs of 0.78 (0.68-0.90) and 1.33 (1.06-1.65), respectively. CONCLUSIONS: We showed that a history of breast cancer has a negative effect on childbirth among young premenopausal women in Korea. Breast cancer survivors should be aware that they have a higher risk for preterm labor and are less likely to have a full-term delivery than women without a history of breast cancer.

Development and validation of a clinical nomogram predicting bladder outlet obstruction via routine clinical parameters in men with refractory nonneurogenic lower urinary tract symptoms.

We aimed to develop and validate a clinical nomogram predicting bladder outlet obstruction (BOO) solely using routine clinical parameters in men with refractory nonneurogenic lower urinary tract symptoms (LUTS). A total of 750 eligible patients ≥50 years of age who had previously not responded (International Prostate Symptom Score [IPSS] improvement <4 points) to at least three different kinds of LUTS medications (including a-blocker) for the last 6 months were evaluated as subcohorts for nomogram development (n = 570) and for split-sample validation (n = 180). BOO was defined as Abrams-Griffiths number ≥40, or 20-39.9 with a slope of linear passive urethral resistance ratio >2 cmH2O ml-1 s-1. A stepwise multivariable logistic regression analysis was conducted to determine the predictors of BOO, and b-coefficients of the final model were selected to create a clinical nomogram. The final multivariable logistic regression model showed that age, IPSS, maximum urinary flow rate, postvoid residual volume, total prostate volume, and transitional zone index were significant for predicting BOO; these candidates were used to develop the final nomogram. The discrimination performance of the nomogram was 88.3% (95% CI: 82.7%-93.0%, P < 0.001), and the nomogram was reasonably well-fitted to the ideal line of the calibration plot. Independent split-sample validation revealed 80.9% (95% CI: 75.5%-84.4%, P < 0.001) accuracy. The proposed BOO nomogram based solely on routine clinical parameters was accurate and validated properly. This nomogram may be useful in determining further treatment, primarily focused on prostatic surgery for BOO, without impeding the detection of possible BOO in men with LUTS that is refractory to empirical medications.

Analysis of factors affecting re-admission after retrograde intrarenal surgery for renal stone.

PURPOSE: To investigate the factors associated with hospital readmission (HR) after retrograde intrarenal surgery (RIRS) among renal stone patients. METHODS: The study included patients who underwent RIRS from June 2011 to December 2017. Patients who were readmitted due to surgery-related complications were evaluated retrospectively. Patient demographics including age, medical comorbidity, body mass indices, ASA score, perioperative parameters and stone factors were compared with total cohorts. HR was defined as visits to the Emergency Room or unplanned admission within 30 days after discharge. The factors affecting HR rates were analyzed using uni- and multi-variate analyses. RESULTS: A total of 572 patients were enrolled into the study. The mean age was 57.6 ± 14.1 years and the mean stone diameter was 13.4 ± 6.2 mm. The mean complication rate was 6.1% and the median hospitalization time was 2.1 ± 3.4 days. HR occurred in 20 patients (3.5%). Compared to non-admission patients, readmitted patients had a higher rate of bilateral RIRS (20.0% vs 12.2%, p = 0.035), number of stones (4.65 vs 2.2, p = 0.041) and higher stone complexity score (4.15 vs 2.11, p = 0.003). Multivariate analysis showed bilateral RIRS (OR 1.091, p = 0.031) and stone complexity (OR 1.405, p = 0.003) were significant factors to predict re-admission after RIRS. CONCLUSION: Patients with complex renal stones or those who underwent bilateral RIRS were more likely to have a higher rate of re-admission. Proper perioperative management to prevent complications should be planned based on these predictive factors.

Does prostate-specific antigen (PSA) mass or free PSA mass improve the accuracy of predicting total prostate volume in relation to obesity in men with biopsy-proven benign prostatic hyperplasia?

We evaluated whether the prostate-specific antigen (PSA) mass or free PSA (fPSA) mass (i.e., absolute amount of total circulating PSA or fPSA protein, respectively), versus serum PSA or fPSA concentration, improves the accuracy of predicting the total prostate volume (TPV) in relation to obesity. Among men whose multicore (≥12) transrectal prostate biopsy was negative, 586 who had a PSA of ≤10 ng ml-1 and underwent the fPSA test prior to biopsy were enrolled. The PSA mass or fPSA mass (µ g) was calculated by multiplying the serum level by plasma volume. At each TPV cut-off point (30 ml, 40 ml, and 50 ml), the areas under the receiver operating characteristics curve (AUCs) of each variable were compared in obesity-based subgroups. AUCs of fPSA and fPSA mass for predicting TPV were significantly larger than those for PSA and PSA mass by 8.7%-12.1% at all cut-off points. Subgroup analyses based on obesity showed that, although PSA mass and fPSA mass enhanced accuracy by 4% (P = 0.031) and 1.8% (P = 0.003), respectively, for determining TPVs of ≥30 ml and ≥50 ml in obese and overweight men, they did not improve the accuracy in most other combinations of the degrees of obesity with TPV cut-off points. Thus, compared with serum PSA or fPSA, the absolute amount of PSA or fPSA protein mass improved the accuracy of predicting TPV in obese men very minimally and only for certain TPV cut-off points. Hence, these indicators may not provide clinically meaningful improvement in predicting TPV in obese men.

Ex Vivo Shear-Wave Elastography of Axillary Lymph Nodes to Predict Nodal Metastasis in Patients with Primary Breast Cancer.

PURPOSE: There is still a clinical need to easily evaluate the metastatic status of lymph nodes during breast cancer surgery. We hypothesized that ex vivo shear-wave elastography (SWE) would predict precisely the presence of metastasis in the excised lymph nodes. METHODS: A total of 63 patients who underwent breast cancer surgery were prospectively enrolled in this study from May 2014 to April 2015. The excised axillary lymph nodes were examined using ex vivo SWE. Metastatic status was confirmed based on the final histopathological diagnosis of the permanent section. Lymph node characteristics and elasticity values measured by ex vivo SWE were assessed for possible association with nodal metastasis. RESULTS: A total of 274 lymph nodes, harvested from 63 patients, were examined using ex vivo SWE. The data obtained from 228 of these nodes from 55 patients were included in the analysis. Results showed that 187 lymph nodes (82.0%) were nonmetastatic and 41 lymph nodes (18.0%) were metastatic. There was significant difference between metastatic and nonmetastatic nodes with respect to the mean (45.4 kPa and 17.7 kPa, p<0.001) and maximum (55.3 kPa and 23.2 kPa, p<0.001) stiffness. The elasticity ratio was higher in the metastatic nodes (4.36 and 1.57, p<0.001). Metastatic nodes were significantly larger than nonmetastatic nodes (mean size, 10.5 mm and 7.5 mm, p<0.001). The size of metastatic nodes and nodal stiffness were correlated (correlation coefficient of mean stiffness, r=0.553). The area under curve of mean stiffness, maximum stiffness, and elasticity ratio were 0.794, 0.802, and 0.831, respectively. CONCLUSION: Ex vivo SWE may be a feasible method to predict axillary lymph node metastasis intraoperatively in patients undergoing breast cancer surgery.

Drug repurposing screening identifies bortezomib and panobinostat as drugs targeting cancer associated fibroblasts (CAFs) by synergistic induction of apoptosis.

Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval. As a result, bortezomib (BTZ), carfilzomib (CFZ), and panobinostat (PST) were identified as anti-CAF drug candidates. It was confirmed that BTZ and PST could decrease the viability of various patients derived CAFs through inducing of caspase-3 mediated apoptosis. Interestingly, combination therapy with BTZ and PST showed better efficacy of inhibiting CAFs than single treatment. The synergistic effect between BTZ and PST on viability of CAFs was observed both in vitro CAF culture and in vivo mouse model. Furthermore, combination therapy with BTZ/PST and conventional anticancer compound docetaxel strongly inhibited tumor growth in xenografts of mouse breast cancer cells with mouse CAFs. In conclusion, our present study revealed that BTZ and PST could significantly reduce the viability of CAFs. Therefore, a combination therapy with BTZ/PST and anticancer drugs might be considered as a new rational for the development of anticancer therapy.

Risk Factors for a False-Negative Result of Sentinel Node Biopsy in Patients with Clinically Node-Negative Breast Cancer.

PURPOSE: Although sentinel lymph node biopsy (SLNB) can accurately represent the axillary lymph node (ALN) status, the false-negative rate (FNR) of SLNB is the main concern in the patients who receive SLNB alone instead of ALN dissection (ALND). MATERIALS AND METHODS: We analyzed 1,886 patientswho underwent ALND after negative results of SLNB,retrospectively. A logistic regression analysis was used to identify risk factors associated with a falsenegative (FN) result. Cox regression model was used to estimate the hazard ratio of factors affecting disease-free survival (DFS). RESULTS: Tumor located in the upper outer portion of the breast, lymphovascular invasion, suspicious node in imaging assessment and less than three sentinel lymph nodes (SLNs) were significant independent risk factors for FN in SLNB conferring an adjusted odds ratio of 2.10 (95% confidence interval [CI], 1.30 to 3.39), 2.69 (95% CI, 1.47 to 4.91), 2.59 (95% CI, 1.62 to 4.14), and 2.39 (95% CI, 1.45 to 3.95), respectively. The prognostic factors affecting DFS were tumor size larger than 2 cm (hazard ratio [HR], 1.86; 95% CI, 1.17 to 2.96) and FN of SLNB (HR, 2.51; 95% CI, 1.42 to 4.42) in SLN-negative group (FN and true-negative), but in ALN-positive group (FN and true-positive), FN of SLNB (HR, 0.64; 95% CI, 0.33 to 1.25) did not affect DFS. CONCLUSION: In patients with risk factors for a FN such as suspicious node in imaging assessment, upper outer breast cancer, less than three harvested nodes, we need attention to find another metastatic focus in non-SLNs during the operation. It may contribute to provide an exact prognosis and optimizing adjuvant treatments.

The Prognostic Impact of Early Change in 18F-FDG PET SUV After Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer.

UNLABELLED: SUV, which is an indicator of the degree of glucose uptake in (18)F-FDG PET, can be applied as a prognostic factor in various malignant tumors. We investigated the prognostic impact of early changes in (18)F-FDG PET uptake in patients with locally advanced breast cancer who received neoadjuvant chemotherapy. METHODS: We retrospectively identified 87 patients who were treated with neoadjuvant chemotherapy followed by surgery for locally advanced breast cancer. All patients underwent (18)F-FDG PET at baseline and after 3 cycles of neoadjuvant chemotherapy, and the SUVmax of the primary tumor was assessed in each scan. Pathologic slides were retrospectively reviewed, and the residual cancer burden (RCB) index was calculated to estimate pathologic response. RCB-0 indicates no residual disease; patients with residual disease were categorized as RCB-1 (minimal residual disease), RCB-2 (moderate residual disease), or RCB-3 (extensive residual disease). RESULTS: There was a negative correlation between reduction in SUVmax and RCB index (r = -0.408; P < 0.001). On multivariate analysis, ΔSUVmax was a significant independent prognostic factor for recurrence-free and overall survival, and the respective adjusted hazard ratios were 0.97 (95% confidence interval, 0.95-0.99; P = 0.001) and 0.97 (95% confidence interval, 0.95-0.99; P = 0.015). When patients were categorized into groups according to pathologic response (RCB index ≤ 1 vs. ≥ 2) and metabolic response (ΔSUVmax ≤ 66.4% vs. > 66.4%), metabolic responders had significantly better recurrence-free and overall survival than metabolic nonresponders among poor-pathologic-response patients. In contrast, among metabolic responders, there was no survival difference according to pathologic response. CONCLUSION: The early change in (18)F-FDG PET SUVmax after third-cycle neoadjuvant chemotherapy is an independent and good prognostic marker beyond pathologic response in patients with locally advanced breast cancer. We suggest that in these patients, the use of ΔSUVmax should be considered not only for the assessment of tumor response but for the prediction of posttreatment outcome.

Association between Seminal Vesicle Invasion and Prostate Cancer Detection Location after Transrectal Systemic Biopsy among Men Who Underwent Radical Prostatectomy.

BACKGROUND: Our hypothesis is that the location of the seminal vesicles near the base of the prostate, the more positive cores are detected in the base, the greater the risk of seminal vesicle invasion. Therefore we investigate the clinical outcomes of base dominant prostate cancer (BDPC) in transrectal ultrasound (TRUS) -guided biopsies compared with anteromiddle dominant prostate cancer (AMPC). METHODS: From November 2003 to June 2014, a total of 990 intermediate and high risk prostate cancer (PCa) patients who underwent radical prostatectomy (RP) were enrolled and stratified into two groups according to proportion of positive cores-BDPC group had ≥ 33.3% ratio of positive cores from the prostate base among all positive cores and AMPC group < 33.3% in systemic biopsy. Between two groups, we compared the rate of pathologic outcomes and biochemical recurrence (BCR). We performed multivariate logistic regression model to confirm the significance of BDPC to seminal vesicle invasion (SVI) and Cox proportional hazard analysis to BCR. RESULTS: Among these 990 PCa patients, the 487 patients in BDPC group had more advanced clinical stage (p<0.001), a higher biopsy GS (p = 0.002), and a higher rate of extracapsular extension (ECE), SVI and BCR (all p<0.001) than AMPC group. The patients in BDPC group had poor BCR free survival rate via Kaplan-meier analysis (p<0.001). The ratio of the base positive cores was a significant predictor to SVI in multivariate analysis (p < 0.001) and significant predictor of BCR in multivariate Cox proportional analysis (hazard ratio: 1.466, p = 0.004). CONCLUSIONS: BDPC in TRUS-guided prostate biopsies was significantly associated with SVI and BCR after adjusting for other clinical factors. Therefore, BDPC should be considered to be a more aggressive tumor despite an otherwise similar cancer profile.

Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma.

BACKGROUND: Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC). METHODS: In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting. We then investigated Tenascin-C immunohistochemical expression in 136 ESCC tissue samples. The clinical relevance of Tenascin-C expression and the correlation between Tenascin-C expression and expression of other factors related to cancer-associated fibroblasts (CAFs) were also determined. RESULTS: Both 250 and 350 kDa sized isoforms of Tenascin-C were expressed only in esophageal cancer tissue not in normal tissue. Furthermore, both isoforms were also identified in all of four CAFs derived from esophageal cancer tissues. Tenascin-C expression was remarkably higher in ESCC than in adjacent non-tumor esophageal epithelium (p < 0.001). Tenascin-C expression in ESCC stromal fibroblasts was associated with patient's age, tumor (pT) stage, lymph node metastasis, clinical stage, and cancer recurrence. Tenascin-C expression in cancer cells was correlated with an increase in tumor-associated macrophage (TAM) population, cancer recurrence, and hypoxia inducible factor1α (HIF1α) expression. Moreover, Tenascin-C overexpression in cancer cells and stromal fibroblasts was an independent poor prognostic factor for overall survival (OS) and disease-free survival (DFS). In the Cox proportional hazard regression model, Tenascin-C overexpression in cancer cells and stromal fibroblasts was a significant independent hazard factor for OS and DFS in ESCC patients in both univariate and multivariate analyses. Furthermore, Tenascin-C expression in stromal fibroblasts of the ESCC patients was positively correlated with platelet-derived growth factor α (PDGFRα), PDGFRß, and smooth muscle actin (SMA) expression. The 5-year OS and DFS rates were remarkably lower in patients with positive expressions of both Tenascin-C and PDGFRα (p < 0.001), Tenascin-C and PDGFRß (p < 0.001), Tenascin-C and SMA (p < 0.001), Tenascin-C and fibroblast activation protein (FAP) (p < 0.001), and Tenascin-C and fibroblast-stimulating protein-1 (FSP1) (p < 0.001) in ESCC stromal fibroblasts than in patients with negative expressions of both Tenascin-C and one of the abovementioned CAF markers. CONCLUSION: Our results show that Tenascin-C is a reliable and significant prognostic factor in ESCC. Tenascin-C may thus be a potent ESCC therapeutic target.

Association between diabetes mellitus and oncological outcomes in bladder cancer patients undergoing radical cystectomy.

OBJECTIVE: To determine the association between diabetes mellitus and oncological outcomes in urothelial bladder cancer patients undergoing radical cystectomy. METHODS: From January 2004 to December 2014, 200 non-metastatic urothelial bladder cancer patients who underwent radical cystectomy were divided into two groups according to diabetes mellitus status at the time of surgery. Kaplan-Meier and Cox regression analysis were used to assess the association between diabetes mellitus and urothelial bladder cancer recurrence-free, cancer-specific and overall mortality. RESULTS: Of the 200 patients, 28 (14%) had diabetes mellitus and presented similar preoperative factors and pathological findings after radical cystectomy, including pathological stage, grade, lymph node invasion and positive surgical margin compared with non-diabetes mellitus patients (n = 172). The 5-year cancer-specific survivals were 92.3% and 62.1% in the non-diabetes mellitus and diabetes mellitus groups, respectively (P = 0.022). Multivariate Cox regression analysis showed that diabetes mellitus was a significant predictor for cancer-specific mortality (hazard ratio 1.785, P = 0.038). The 5-year overall survival rate was 92.1% and 59.4% in the non-diabetes mellitus and diabetes mellitus groups, respectively (P = 0.014), and diabetes mellitus was a significant factor for overall mortality by multivariate Cox regression analysis (hazard ratio 1.281, P = 0.042). CONCLUSIONS: Among bladder cancer patients who underwent radical cystectomy, the diabetes mellitus patients had worse cancer-specific mortality and overall mortality outcomes than the non-diabetes mellitus patients. The mechanism of association between diabetes mellitus and urothelial bladder cancer should be investigated to validate the present results in a future prospective study.

Therapeutic effect of Active Hexose-Correlated Compound (AHCC) combined with CpG-ODN (oligodeoxynucleotide) in B16 melanoma murine model.

While Active Hexose Correlated Compound (AHCC) and CpG oligodeoxynucleotide (ODN) are separately known to modulate oxidative stress and immune responses in cancer patients, the combined effect of these two compounds is unknown. To clarify this, we investigated whether AHCC plus KSK-CpG ODN would be therapeutic in B16 melanoma mouse model, if so, and how in reduction-oxidation (redox) balance and cytokines network. We found that treatment groups (AHCC only, KSK-CpG ODN only and AHCC/KSK-CpG ODN) markedly reduced (p<0.001) tumor size when compared to the positive control (PC) group. The total white blood cell (WBC) of AHCC only and KSK-CpG ODN only-treated groups showed significant lower counts than that of PC group. Next, the production of nitric oxide (NO) was significantly increased (p<0.01) in AHCC/KSK-CpG ODN group compared to the PC group. Further, the redox balance was improved in AHCC/KSK-CpG ODN group through significantly low (p<0.001) reactive oxygen species (ROS) production and significantly high (p<0.05) glutathione peroxidase (GPx) activity compared to the PC group. Finally, AHCC/KSK-CpG ODN (p<0.01) and KSK-CpG ODN (p<0.001)-treated groups augmented tumor immune surveillance as shown by significantly increased level of anti-inflammatory cytokine (IL-10) and significantly decreased (p<0.05) level of pro-tumorigenic IL-6 of AHCC/KSK-CpG ODN treated group as compared to the PC group. Collectively, our study indicates therapeutic effect of Active Hexose-Correlated Compound (AHCC) combined with KSK-CpG ODN in B16 melanoma murine model via balancing redox and cytokines network.

Local control of brain metastasis: treatment outcome of focal brain treatments in relation to subtypes.

PURPOSE: To investigate treatment options for local control of metastasis in the brain, we compared focal brain treatment (FBT) with or without whole brain radiotherapy (WBRT) vs. WBRT alone, for breast cancer patients with tumor relapse in the brain. We also evaluated treatment outcomes according to the subtypes. METHODS: We conducted a retrospective review of breast cancer patients with brain metastasis after primary surgery. All patients received at least one local treatment for brain metastasis. Surgery or stereotactic radiosurgery was categorized as FBT. Patients were divided into two groups: the FBT group received FBT±WBRT, whereas the non-FBT group received WBRT alone. Subtypes were defined as follows: hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and triple-negative (TN). We examined the overall survival after brain metastasis (OSBM), brain metastasis-specific survival (BMSS), and brain metastasis-specific progression-free survival (BMPFS). RESULTS: A total of 116 patients were identified. After a median follow-up of 50.9 months, the median OSBM was 11.5 months (95% confidence interval, 9.0-14.1 months). The FBT group showed significantly superior OSBM and BMSS. However, FBT was not an independent prognostic factor for OSBM and BMSS on multivariate analyses. In contrast, multivariate analyses showed that patients who underwent surgery had improved BMPFS, indicating local control of metastasis in the brain. FBT resulted in better BMPFS in patients with HR-negative/HER2-positive cancer or the TN subtype. CONCLUSION: We found that patients who underwent surgery experienced improved local control of brain metastasis, regardless of its extent. Furthermore, FBT showed positive results and could be considered for better local control of brain metastasis in patients with aggressive subtypes such as HER2-positive and TN.

Genome-wide detection of allelic genetic variation to predict biochemical recurrence after radical prostatectomy among prostate cancer patients using an exome SNP chip.

PURPOSES: Genetic variations among prostate cancer patients who underwent radical prostatectomies were evaluated to predict biochemical recurrence, and used to develop a clinical-genetic model that combines data on clinicopathological factors of prostate cancer and individual genetic variations. MATERIALS AND METHODS: We genotyped 242,186 SNPs on a custom HumanExome BeadChip v1.0 (Illuminam Inc.) from the blood DNA of 776 PCa patients who underwent radical prostatectomy. Genetic data were analyzed to calculate an odds ratio as an estimate of the relative risk of biochemical recurrence. And we compared accuracies from the multivariate model incorporating clinicopathological factors between included and excluded selected lead single nucleotide polymorphisms. Biochemical recurrence-free survival outcomes also analyzed using these genetic variations. RESULTS: Genetic array analysis indicated that eight single nucleotide polymorphisms (rs77080351, rs200944490, rs2071292, rs117237810, rs191118242, rs4965121, rs61742396, and rs6573513) were significant to predict biochemical recurrence after radical prostatectomy. When a multivariate model incorporating clinicopathological factors was devised to predict biochemical recurrence, the predictive accuracy of model was 85.1 %. By adding in two individual variations of single nucleotide polymorphisms in the multivariate model, the predictive accuracy increased to 87.7 % (P = 0.045). With three variations of single nucleotide polymorphisms, the predictive accuracy further improved to 89.0 % (P = 0.025). These genetic variations had a significantly decreased biochemical recurrence-free survival rate. CONCLUSIONS: Based on exome array, the selected single nucleotide polymorphisms were predictors for biochemical recurrence. The addition of individualized genetic information effectively enhanced the predictive accuracy of biochemical recurrence among prostate cancer patients who underwent radical prostatectomy.

A clinicogenetic model to predict lymph node invasion by use of genome-based biomarkers from exome arrays in prostate cancer patients.

PURPOSE: Genetic variations among prostate cancer (PCa) patients who underwent radical prostatectomy (RP) and pelvic lymph node dissection were evaluated to predict lymph node invasion (LNI). Exome arrays were used to develop a clinicogenetic model that combined clinical data related to PCa and individual genetic variations. MATERIALS AND METHODS: We genotyped 242,186 single-nucleotide polymorphisms (SNPs) by using a custom HumanExome BeadChip v1.0 (Illumina Inc.) from the blood DNA of 341 patients with PCa. The genetic data were analyzed to calculate an odds ratio as an estimate of the relative risk of LNI. We compared the accuracies of the multivariate logistic model incorporating clinical factors between the included and excluded selected SNPs. The Cox proportional hazard models with or without genetic factors for predicting biochemical recurrence (BCR) were analyzed. RESULTS: The genetic analysis indicated that five SNPs (rs75444444, rs8055236, rs2301277, rs9300039, and rs6908581) were significant for predicting LNI in patients with PCa. When a multivariate model incorporating clinical factors was devised to predict LNI, the predictive accuracy of the multivariate model was 80.7%. By adding genetic factors in the aforementioned multivariate model, the predictive accuracy increased to 93.2% (p=0.006). These genetic variations were significant factors for predicting BCR after adjustment for other variables and after adding the predictive gain to BCR. CONCLUSIONS: Based on the results of the exome array, the selected SNPs were predictors for LNI. The addition of individualized genetic information effectively enhanced the predictive accuracy of LNI and BCR among patients with PCa who underwent RP.

Prospective evaluation of the feasibility of sentinel lymph node biopsy in breast cancer patients with negative axillary conversion after neoadjuvant chemotherapy.

PURPOSE: Tumor response to neoadjuvant chemotherapy (NAC) may adversely affect the identification and accuracy rate of sentinel lymph node biopsy (SLNB). This study was conducted to evaluate the feasibility of SLNB in node-positive breast cancer patients with negative axillary conversion after NAC. MATERIALS AND METHODS: Ninety-six patients with positive nodes at presentation were prospectively enrolled. (18)Fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET) and ultrasonography were performed before and after NAC. A metastatic axillary lymph node was defined as positive if it was positive upon both (18)F-FDG PET and ultrasonography, while it was considered negative if it was negative upon both (18)F-FDG PET and ultrasonography. RESULTS: After NAC, 55 cases (57.3%) became clinically node-negative, while 41 cases (42.7%) remained node-positive. In the entire cohort, the sentinel lymph node (SLN) identification and false-negative rates were 84.3% (81/96) and 18.4% (9/49), respectively. In the negative axillary conversion group, the results of SLNB showed an 85.7% (48/55) identification rate and 16.7% (4/24) false-negative rate. CONCLUSION: For breast cancer patients with clinically positive nodes at presentation, it is difficult to conclude whether the SLN accurately represents the metastatic status of all axillary lymph nodes, even after clinically negative node conversion following NAC.

Metastasis-Free Interval Is Closely Related to Tumor Characteristics and Has Prognostic Value in Breast Cancer Patients with Distant Relapse.

PURPOSE: We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes. METHODS: We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short (<2 years), intermediate (≥2 years and <5 years), or long (≥5 years). Overall survival after metastasis (OSM) was estimated. RESULTS: Patients with a shorter MFI were younger, more likely to have initial metastasis to visceral organs, and had a larger tumor with a higher stage and grade as well as a higher rate of nodal involvement at initial diagnosis. Among 136 patients with known disease subtypes, shorter MFI was associated with the triple-negative subtype while longer MFI was associated with the hormone receptor-positive/human epidermal growth factor receptor 2 negative subtype. Mortality after metastasis declined sharply with increasing MFI up to approximately 2 years, and continued gradually declining between 2 and 5 years. An MFI longer than 5 years did not add any survival benefit. MFI was a significant prognostic factor for OSM independent of nodal status, stage, metastatic site, and hormone receptor status of the metastasized cancer. CONCLUSION: MFI is closely related to biological characteristics of both primary tumors and their metastases, and has a prognostic value for survival after metastasis. We therefore suggest investigation into treatments targeting improvement of MFI as a potential novel strategy.

Survival benefit of zoledronic Acid in postmenopausal breast cancer patients receiving aromatase inhibitors.

PURPOSE: A growing body of evidence indicates that zoledronic acid (ZA) can improve the clinical outcome in patients with breast cancer and low estrogen levels. In the present study, we aimed to investigate the survival benefit of ZA administration in postmenopausal Korean women with breast cancer who were also receiving aromatase inhibitors. METHODS: Between January 2004 and December 2010, 235 postmenopausal breast cancer patients undergoing aromatase inhibitor therapy were investigated. All patients were postmenopausal, as confirmed by laboratory tests. Of these patients, 77 received adjuvant upfront ZA for at least 1 year in addition to conventional adjuvant treatment. The remaining 158 patients never received ZA and were treated according to the St. Gallen guidelines. RESULTS: The baseline characteristics for ZA treatment were not different between the two groups. The median follow-up time was 62 months, and the patients who received ZA in addition to aromatase inhibitors showed a better recurrence-free survival compared to those who received aromatase inhibitors alone (p=0.035). On multivariate analysis, the patients who received ZA showed a better recurrence-free survival independent of the tumor size, nodal status, progesterone receptor, and histological grade. For this model, Harrell c index was 0.743. The hazard ratio of ZA use for recurrence-free survival was 0.12 (95% confidence interval, 0.01-0.99). CONCLUSION: Our findings suggest that upfront use of ZA as part of adjuvant treatment can offer a survival benefit to postmenopausal breast cancer patients receiving aromatase inhibitor treatment.

[18F]-fluorodeoxyglucose positron emission tomography can contribute to discriminate patients with poor prognosis in hormone receptor-positive breast cancer.

BACKGROUND: Patients with hormone receptor-positive breast cancer typically show favorable survival. However, identifying individuals at high risk of recurrence among these patients is a crucial issue. We tested the hypothesis that [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans can help predict prognosis in patients with hormone receptor-positive breast cancer. METHODS: Between April 2004 and December 2008, 305 patients with hormone receptor-positive breast cancer who underwent FGD-PET were enrolled. Patients with luminal B subtype were identified by positivity for human epidermal growth factor receptor-2 (HER2) or high Ki67 (≥14%) according to criteria recently recommended by the St. Gallen panelists. The cut-off value of SUVmax was defined using the time-dependent receiver operator characteristic curve for recurrence-free survival (RFS). RESULTS: At a median follow up of 6.23 years, continuous SUVmax was a significant prognostic factor with a hazard ratio (HR) of 1.21 (p = 0.021). The cut-off value of SUVmax was defined as 4. Patients with luminal B subtype (n = 82) or high SUVmax (n = 107) showed a reduced RFS (p = 0.031 and 0.002, respectively). In multivariate analysis for RFS, SUVmax carried independent prognostic significance (p = 0.012) whereas classification with immunohistochemical markers did not (p = 0.274). The Harell c-index was 0.729. High SUVmax was significantly associated with larger tumor size, positive nodes, HER2 positivity, high Ki67 (≥14%), high tumor grade, and luminal B subtype. CONCLUSIONS: Among patients with hormone receptor-positive breast cancer, FDG-PET can help discriminate patients at high risk of tumor relapse.

Long-term survival analysis of korean breast cancer patients at a single center: improving outcome over time.

PURPOSE: The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time. MATERIALS AND METHODS: A total of 1889 patients with known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed. RESULTS: At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III. CONCLUSION: In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.