A nomogram constructed using intraoperative ex vivo shear-wave elastography precisely predicts metastasis of sentinel lymph nodes in breast cancer

OBJECTIVE: To develop a nomogram and validate its use for the intraoperative evaluation of nodal metastasis using shear-wave elastography (SWE) elasticity values and nodal size METHODS: We constructed a nomogram to predict metastasis using ex vivo SWE values and ultrasound features of 228 axillary LNs from fifty-five patients. We validated its use in an independent cohort comprising 80 patients. In the validation cohort, a total of 217 sentinel LNs were included. RESULTS: We developed the nomogram using the nodal size and elasticity values of the development cohort to predict LN metastasis; the area under the curve (AUC) was 0.856 (95% confidence interval (CI), 0.783-0.929). In the validation cohort, 15 (7%) LNs were metastatic, and 202 (93%) were non-metastatic. The mean stiffness (23.54 and 10.41 kPa, p = 0.005) and elasticity ratio (3.24 and 1.49, p = 0.028) were significantly higher in the metastatic LNs than those in the non-metastatic LNs. However, the mean size of the metastatic LNs was not significantly larger than that of the non-metastatic LNs (8.70 mm vs 7.20 mm, respectively; p = 0.123). The AUC was 0.791 (95% CI, 0.668-0.915) in the validation cohort, and the calibration plots of the nomogram showed good agreement. CONCLUSIONS: We developed a well-validated nomogram to predict LN metastasis. This nomogram, mainly based on ex vivo SWE values, can help evaluate nodal metastasis during surgery. KEY POINTS: • A nomogram was developed based on axillary LN size and ex vivo SWE values such as mean stiffness and elasticity ratio to easily predict axillary LN metastasis during breast cancer surgery. • The constructed nomogram presented high predictive performance of sentinel LN metastasis with an independent cohort. • This nomogram can reduce unnecessary intraoperative frozen section which increases the surgical time and costs in breast cancer patients.ope

Low PR in ER(+)/HER2(-) breast cancer: high rates of TP53 mutation and high SUV

On the basis of TP53 mutations and standardized uptake values (SUVs) from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), we sought to enhance our knowledge of the biology underlying low progesterone receptor (PR) expression in estrogen receptor (ER)-positive/human epidermal growth factor receptor-2 (HER2)-negative tumors. This study included 272 patients surgically treated for ER-positive, HER2-negative breast cancer and who had undergone TP53 gene sequencing. Of these, 229 patients also underwent 18F-FDG PET or PET/CT. Mutational analysis of exons 5 to 9 of the TP53 gene was conducted using polymerase chain reaction amplification and direct sequencing. The SUVs were measured using 18F-FDG-PET scan images. We found that twenty-eight (10.3%) tumors had a somatic TP53 mutation. The TP53 mutation rate was significantly higher in low-PR tumors than in high-PR tumors (17.1% vs. 7.9%, P = 0.039). Low-PR tumors had significantly higher median SUVs than high-PR tumors (P = 0.046). The multivariable analysis revealed that SUV and age remained independent variables associated with low PR expression. An adverse impact of low PR expression on recurrence-free survival was observed in the multivariable Cox regression hazard model. We provide clinical evidence that genetic alteration of the TP53 gene and dysregulated glucose metabolism partly involve low PR expression in ER-positive and HER2-negative breast cancer.ope

Repeat Sentinel Lymph Node Biopsy for Ipsilateral Breast Tumor Recurrence After Breast Conserving Surgery With Sentinel Lymph Node Biopsy: Pooled Analysis Using Data From a Systematic Review and Two Institutions

Introduction: Best surgical approach of axillary staging remains controversial in locally recurrent breast cancer. We evaluated the reliability of repeat sentinel lymph node biopsy (reSLNB) in patients with ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) with sentinel lymph node biopsy (SLNB) in terms of identification rate (IR) and false negative rate (FNR). To address the FNR, we identified patients who underwent sequential axillary lymph node dissection (ALND) after reSLNB. Methods: A systematic search of PubMed, EMBASE, and Cochrane Library were conducted to identify patient-level data from articles. We searched for data of patients who underwent BCS with SLNB for primary breast cancer and who underwent sequential ALND after reSLNB due to local recurrence. Patients data was also identified by the same criteria at two institutions. Results: In total, 197 peer-reviewed publications were obtained, of which 20 included patients who met the eligibility criteria. Data from 464 patients were collected. From the two institutions, 31 patients were identified. A total of 495 patients were pooled. The IR of reSLNB was 71.9% (356/495). To address the FNR of reSLNB, 171 patients who underwent ALND after reSLNB were identified. The FNR and accuracy of reSLNB were 9.4% (5/53) and 97.1% (165/170), respectively. Conclusion: Our pooled data analysis showed that the FNR of reSLNB is lower than 10%, indicating that this operation is a reliable axillary surgery in patients with IBTR after they underwent BCS.ope

High A20 expression negatively impacts survival in patients with breast cancer

BACKGROUND: A20 protein has ubiquitin-editing activities and acts as a key regulator of inflammation and immunity. Previously, our group showed that A20 promotes tumor metastasis through multi-monoubiquitylation of SNAIL1 in basal-like breast cancer. Here, we investigated survival outcomes in patients with breast cancer according to A20 expression. PATIENTS AND METHODS: We retrospectively collected tumor samples from patients with breast cancer. Immunohistochemistry (IHC) with an A20-specific antibody was performed, and survival outcomes were analyzed. RESULTS: A20 expression was evaluated in 442 patients. High A20 expression was associated with advanced anatomical stage and young age. High A20 expression showed significantly inferior recurrence-free-survival and overall-survival (P<0.001 and P<0.001, respectively). Multivariate analysis showed that A20 was an independent prognostic marker for RFS (HRs: 2.324, 95% CIs: 1.446-3.736) and OS (HRs: 2.629, 95% CIs: 1.585-4.361). In human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer (TNBC) subtypes, high A20 levels were associated with poor OS. CONCLUSION: We found that A20 expression is a poor prognostic marker in breast cancer. The prognostic impact of A20 was pronounced in aggressive tumors, such as HER2-positive and TNBC subtypes. Our findings suggested that A20 may be a valuable target in patients with aggressive breast cancer.ope

Relationship of the standard uptake value of 18 F-FDG-PET-CT with tumor-infiltrating lymphocytes in breast tumors measuring ≥ 1 cm

Evidence suggests that tumor cells and tumor-infiltrating lymphocytes (TILs) compete for glucose in the tumor microenvironment and that tumor metabolic parameters correlate with localized immune markers in several solid tumors. We investigated the relationship of the standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET-CT) with stromal TIL levels in breast cancer. We included 202 patients who underwent preoperative 18F-FDG-PET-CT and had a tumor measuring ≥ 1 cm. Maximum SUV (SUVmax) was determined using 18F-FDG-PET-CT. Multiple logistic regression was used to identify factors related to high TIL levels (≥ 40%). All tumors were treatment naïve. A significant and weak correlation existed between continuous SUVmax and continuous TIL levels (p = 0.002, R = 0.215). Tumors with high SUVmax (≥ 4) had higher mean TIL levels than those with low SUVmax (< 4). In multivariable analysis, continuous SUVmax was an independent factor associated with high TIL levels; each 1-unit increment in SUVmax corresponded to an odds ratio of 1.14 (95% confidence interval: 1.01-1.29) for high TIL levels. Our study implies that SUV is associated with TILs in breast cancer and provides clinical evidence that elevated glucose uptake by breast tumors can predict the immune system-activated tumor micromilieu.ope

Immediate Breast Reconstruction Does Not Have a Clinically Significant Impact on Adjuvant Treatment Delay and Subsequent Survival Outcomes

Purpose: The use of immediate breast reconstruction (IBR) has been debated because it may be a causative factor in adjuvant treatment delay and may subsequently increase the probability of recurrence. We investigated whether IBR was related to adjuvant treatment delay and survival outcomes. Methods: We retrospectively analyzed the duration from operation to adjuvant treatment administration and survival outcomes according to IBR status among patients with breast cancer who underwent mastectomy followed by adjuvant chemotherapy from January 2005 to December 2014. Propensity score matching was performed to balance the clinicopathologic baseline characteristics between patients who did and did not undergo IBR. Results: Of 646 patients, 107 (16.6%) underwent IBR, and the median follow-up was 72 months. The median duration from surgery to adjuvant chemotherapy was significantly longer in patients who underwent IBR than in those who did not (14 vs. 12 days, respectively, p = 0.008). Based on propensity score matching, patients who underwent IBR received adjuvant therapy 3 days later than those who did not (14 vs. 11 days, respectively, p = 0.044). The duration from surgery to post-mastectomy radiation therapy (PMRT) did not significantly differ between the 2 groups. Local recurrence-free survival, regional recurrence-free survival, systemic recurrence-free survival, and overall survival were also not significantly different between the 2 groups (p = 0.427, p = 0.445, p = 0.269, and p = 0.250, respectively). In the case-matched cohort, survival outcomes did not change. Conclusion: IBR was associated with a modest increase in the duration from surgery to chemotherapy that was statistically but not clinically significant. Moreover, IBR had no influence on PMRT delay or survival outcomes, suggesting that it is an acceptable option for patients with non-metastatic breast cancer undergoing mastectomy.ope

Axillary response according to neoadjuvant single or dual human epidermal growth factor receptor 2 (HER2) blockade in clinically node-positive, HER2-positive breast cancer

Incorporating dual human epidermal growth factor receptor 2 (HER2) blockade into neoadjuvant systemic therapy (NST) led to higher response in patients with HER2-positive breast cancer. However, axillary response to treatment regimens, including single or dual HER2 blockade, in patients with clinically node-positive breast cancer remains uncertain. Our study aimed to examine the pathologic axillary response according to the type of NST, that is, single or dual HER2 blockade. In our study, 546 patients with clinically node-positive, HER2-positive breast cancer who received NST followed by axillary surgery were retrospectively selected and divided into three groups: chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab. The primary outcome was the axillary pathologic complete response (pCR). Among 471 patients undergoing axillary lymph node dissection, the axillary pCR rates were 43.5%, 74.5% and 68.8% in patients who received chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab, respectively. There was no difference in axillary pCR rates between patients who received single or dual HER2 blockade (P = .379). Among patients receiving chemotherapy + trastuzumab, patients without breast pCR had the greatest risk for residual axillary metastases (relative risk, 9.8; 95% confidence interval, 3.2-14.9; P < .0001). In conclusion, adding trastuzumab to chemotherapy increased the axillary pCR rate in patients with clinically node-positive, HER2-positive breast cancer; furthermore, dual HER2-blockade with trastuzumab and pertuzumab did not elevate the axillary response compared with trastuzumab alone. Breast pCR could be a strong predictor for axillary pCR in clinically node-positive patients treated with HER2-targeting therapy.ope

Radiotherapy-Induced High Neutrophil-to-Lymphocyte Ratio is a Negative Prognostic Factor in Patients with Breast Cancer

Radiotherapy (RT) is the standard of care following breast-conserving operation in breast cancer patients. The neutrophil-to-lymphocyte ratio (NLR) reflects the systemic change caused as a result of the radiotherapy. We aimed to evaluate the association between RT and the change in NLR following the receipt of RT, and to investigate the prognostic impact. We retrospectively reviewed NLR values of breast cancer patients taken before the administration of the first and the last session of RT. The cut-off point for the NLR was determined using the Youden index and receiver operating characteristic (ROC) curve within the training set. Recurrence-free survival (RFS), distant metastasis free survival, and overall survival were the main outcomes. Patients with an NLR higher than 3.49 after RT were classified to an RT-induced high NLR group and showed a significantly higher recurrence rate compared to those with low NLR (p < 0.001). In a multivariate Cox proportional hazards model, RT-induced high NLR remained a significant prognostic factor (HR 2.194, 95% CI 1.230-3.912, p = 0.008 for tumor recurrence. We demonstrated that an increase in NLR over the course of RT has a negative impact on survival, putting these patients with RT-susceptible host immunity at a higher risk of tumor recurrence.ope

히르슈슈프룽병에서의 one-stage transanal endorectal pull-through 술식과 Duhamel pull-through 술식의 비교

의학전문대학원Purpose: This study aimed to compare the operative results of the one-stage transanal endorectal pull-through operation (TERPT) with those of the Duhamel pull-through operation (DPT) for Hirschsprung’s disease, including long-term functional outcomes. Methods: Clinical data and postoperative courses of Hirschsprung’s disease patients who had aganglionic bowel confined to the rectosigmoid and who underwent TERPT or DPT prior to 1 year of age between 2001 and 2013 at Severance Children’s Hospital were reviewed and analyzed. Results: Fifty-one patients underwent TERPT, and 50 patients underwent DPT. Age at the time of the pull-through operation is significantly younger in the TERPT group (1.7 ± 1.9 vs. 4.0 ± 2.4 months, p<0.001), and the mean operation time of TERPT was significantly shorter than that of DPT (154.6 ± 52.4 vs. 196.6 ± 65.0 min, p=0.001). Operation-related complications among those in the TERPT group were significantly fewer than among those in the DPT group (0 vs. 18%, p=0.001). However, hospital stays following the operation did not significantly differ (9.6 ± 3.1 vs. 11.4 ± 9.3 days, p=0.200). The readmission rate was also significantly lower in the TERPT group (39.2 vs. 64.0%, p=0.013). With respect to the long-term functional outcome, the TERPT group had a significantly lower incidence of soiling (4.3 vs. 43.2%, p<0.001) and constipation (2.1 vs. 16.2%, p=0.040). Conclusion: This study results showed significantly better postoperative clinical outcomes in the TERPT group. These results support the superiority of the TERPT procedure over DPT.open석

Local Treatment in Addition to Endocrine Therapy in Hormone Receptor-Positive and HER2-Negative Oligometastatic Breast Cancer Patients: A Retrospective Multicenter Analysis

Background: Recent trials have provided robust evidence demonstrating that endocrine therapy with/without targeted therapy, such as cyclin-dependent kinase 4/6 inhibitors or mTOR (mammalian target of rapamycin) inhibitors, effectively halts disease progression in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We investigated the survival impact of local treatment of metastases as a first-line treatment after metastasis in HR-positive and HER2-negative breast cancer patients with a very low metastatic volume. Materials and methods: From a retrospectively constructed database for three institutes, we identified HR-positive and HER2-negative breast cancer patients with recurrent distant oligometastatic disease after initially curative treatment. De novo stage 4 patients were excluded, and only those with recurrent metastatic disease were included. Oligometastatic disease was defined as follows: (1) ≤2 metastatic lesions in a single organ, (2) a maximal diameter ≤3 cm, and (3) organ involvement, including the lung, liver, adrenal gland, bone, or distant lymph nodes. Local treatment comprised surgery or radiotherapy. Progression-free survival (PFS) and overall survival (OS) were investigated. Results: Forty-nine patients were included; 33 underwent local treatment. Of these 33 patients, 5 underwent surgical resection and 27 received radiotherapy. One patient underwent both surgical resection and radiotherapy. Median PFS was significantly longer among the patients with local treatment than among the patients without local treatment (30.0 vs. 18.0 months, p = 0.049). In multivariate analysis, local treatment was shown to prolong PFS. However, median OS after metastasis did not differ with regard to local treatment (72.3 vs. 91.0 months, p = 0.272). Conclusion: We showed that local treatment could positively affect disease progression in HR-positive and HER2-negative oligometastatic breast cancer.restrictio