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Competing Interests: Disclosures: The authors declare no conflicts of interest.

Background: We investigated the perioperative outcome and oncologic safety of performing nipple-sparing mastectomy (NSM) through a single axillary incision (NSM-SAI) compared with performing NSM through a conventional incision (NSM-C)., Methods: We retrospectively reviewed 725 patients who underwent NSM for breast cancer between January 2010 and December 2023; 333 patients who underwent NSM with immediate reconstruction (IR) were enrolled. Surgical outcomes and oncologic outcomes of NSM-C (n = 184), NSM performed through SAI with a freehand approach (NSM-SAI-F; n = 92), and with an endoscopic approach (NSM-SAI-E; n = 57) were demonstrated. The risk factors for resection margins, nipple-areolar complex (NAC), and skin flap necrosis were evaluated separately for NSM-C and NSM-SAI., Results: NAC and skin flap necrosis occurrence rates among the NSM-C, NSM-SAI-F, and NSM-SAI-E groups were similar (insignificant), regardless of autologous or prosthesis reconstruction. The tumor-to-nipple distance among patients who underwent NSM-C was an independent risk factor for NAC necrosis in the NSM-C group (odds ratio [OR] 6.02, p = 0.007); being overweight and tumor location in the lower breast were risk factors for skin necrosis in the NSM-C group (OR 3.36, p = 0.041; and OR 4.32, p = 0.011, respectively). These risk factors were not associated with the NSM-SAI group. The three groups had comparable positive resection margins, local recurrence-free survival, and distant metastasis-free survival rates (p = 0.857, 0.543, and 0.975, respectively)., Conclusions: NSM-SAI combined with IR by the freehand or endoscopic approaches can provide good aesthetic outcomes and oncologic safety for well-selected patients with breast cancer. The risk factors for NAC and skin flap necrosis differ between the NSM-SAI and NSM-C groups., Competing Interests: Disclosures: Ruoh-Yun Gau, Hsu-Huan Chou, Hsiu-Pei Tsai, Shih-Che Shen, Wen-Ling Kuo, Chia-Hui Chu, Hui-yu Ho, Jung-Ju Huang, Yung-Chang Lin, Yi-Ting Huang, Chi-Chang Yu, and Shin-Cheh Chen have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017., (© 2024. The Author(s).)

Background: Due to the presence of other comorbidities and multi-therapeutic modalities in breast cancer, renally cleared chemotherapeutic regimens may cause nephrotoxicity. The aim of this retrospective study is to compare the chemotherapy types and outcomes in breast cancer patients with or without chronic renal disease., Patients and Methods: We retrospectively enrolled 62 female patients with breast cancer and underlying late stages (stage 3b, 4, and 5) of chronic kidney disease (CKD) treated from 2000 to 2017. They were propensity score-matched 1:1 with patients in our database with breast cancer and normal renal function (total n = 124)., Results: The main subtype of breast cancer was luminal A and relatively few patients with renal impairment received chemotherapy and anti-Her-2 treatment. The breast cancer patients with late-stage CKD had a slightly higher recurrent rate, especially at the locally advanced stage. The 5-year overall survival was 90.1 and 71.2% for patients without and with late-stage CKD, but the breast cancer-related mortality rate was 88.9 and 24.1%, respectively. In multivariate analyses, dose-reduced chemotherapy was an independent negative predictor of 5-year recurrence-free survival and late-stage CKD was associated with lower 5-year overall survival rate., Conclusions: Breast cancer patients with late-stage CKD may receive insufficient therapeutic modalities. Although the recurrence-free survival rate did not differ significantly by the status of CKD, patients with breast cancer and late-stage CKD had shorter overall survival time but a lower breast cancer-related mortality rate, indicated that the mortality was related to underlying disease., (© 2023. The Author(s).)

This study aimed to investigate the dose parameters and incidence of radiotherapy (RT)-associated toxicity in patients with left breast cancer (LBC) treated with proton-RT, compared with photon-RT. We collected data from 111 patients with LBC who received adjuvant RT in our department between August 2021 and March 2023. Among these patients, 24 underwent proton-RT and 87 underwent photon-RT. In addition to the dosimetric analysis for organs at risk (OARs), we measured NT-proBNP levels before and after RT. Our data showed that proton-RT improved dose conformity and reduced doses to the heart and lungs and was associated with a lower rate of increased NT-proBNP than did photon-RT. Regarding skin toxicity, the Dmax for 1 c.c. and 10 c.c. and the average dose to the skin-OAR had predictive roles in the risk of developing radiation-induced dermatitis. Although pencil beam proton-RT with skin optimization had a dose similar to that of skin-OAR compared with photon-RT, proton-RT still had a higher rate of radiation dermatitis (29%) than did photon RT (11%). Using mice 16 days after irradiation, we demonstrated that proton-RT induced a greater increase in interleukin 6 and transforming growth factor-β1 levels than did photon-RT. Furthermore, topical steroid ointment reduced the inflammatory response and severity of dermatitis induced by RT. In conclusion, we suggest that proton-RT with skin optimization spares high doses to OARs with acceptable skin toxicity. Furthermore, prophylactic topical steroid treatment may decrease radiation dermatitis by alleviating proton-induced inflammatory responses in vivo., Competing Interests: None., (AJCR Copyright © 2023.)

Objectives: In the women with compressed thin thickness (≦ 3 cm), mammographic guiding vacuum-assist breast biopsy (MG-VABB) is a technical challenge. We herein report their performance of MG-VABB on suspicious microcalcification by modern mammography., Methods: We retrospectively reviewed the consecutive MG-VABB in our hospital from February 2019 to January 2021. All the patients received biopsy because of suspicious microcalcifications discovered by mammography and had at least one-year post-biopsy follow-up., Results: We reviewed 745 consecutive patients revealing 195 with compressed thin breasts ≦ 3 cm (mean age: 50.12 ± 7.0; breast thickness: 24.99 mm range 11.6-30 mm). Of the 191 patients received biopsy, the microcalcification retrieval rate was 97.9%. Using the half-open notch biopsy or horizontal needle approach, the biopsies were technically achieved in 30.4% and 9.4% of patients respectively. Regarding to the gold standard of surgicohistology, the cancer sensitivities was 88.46% and the atypia upgrade rate was 16.67%. There was no statistical difference of the procedure time between stereotactic guided and tomosynthesis guided., Conclusions: The modern MG-VABB has technically improve the performance of biopsy to the patients with compressed thin breasts (≦ 3 cm), revealing approximate results to those breasts > 3 cm. The diagnosis helps the management of suspicious microcalcifications discovered by mammography., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Adequate axillary lymph node (ALN) staging is critical for patients with invasive breast cancer. However, neoadjuvant chemotherapy (NAC) was associated with a lower risk of ALN metastasis compared with those who underwent primary surgery among clinically node-negative (cN0) patients. This study aimed to investigate the factors associated with ALN status among patients with cN0 breast cancer undergoing NAC. A total of 222 consecutive patients with cN0 breast cancer undergoing NAC between January 2012 and December 2021 were reviewed. Univariate and multivariate analyses were performed to compare factors associated with positive ALN status. Seventeen patients (7.7%) had ALNs metastases. Here, 90 patients (40.5%) achieved pathologic complete response in the breast (breast-pCR), and all had negative ALN status. Lymphovascular invasion (odds ratio: 29.366, p < 0.0001) was an independent risk predictor of ALN metastasis in all study populations. Among patients without breast-pCR, mastectomies were performed more frequently in patients with ALN metastasis (52.9%) than in those without metastasis (20.9%) (p = 0.013). Our findings support the omission of axillary surgery in patients who achieve breast-pCR. Prospective studies are needed to confirm the feasibility of a future two-stage surgical plan for breast-conserving surgery in patients who are likely to achieve breast-pCR during clinical evaluation.

Triple-negative breast cancer (TNBC) is treated with neoadjuvant chemotherapy (NAC). The response to NAC, particularly the probability of a complete pathological response (pCR), guides the surgical approach and adjuvant therapy. We developed a prediction model using a nomogram integrating blood tests and pre-treatment ultrasound findings for predicting pCR in patients with stage II or III operable TNBC receiving NAC. Clinical data before and after the first cycle of NAC collected from patients between 2012 and 2019 were analyzed using univariate and multivariate analyses to identify correlations with pCR. The coefficients of the significant parameters were calculated using logistic regression, and a nomogram was developed based on the logistic model to predict the probability of pCR. Eighty-eight patients were included. Five parameters correlated with the probability of pCR, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte (PLR) ratio, percentage change in PLR, presence of echogenic halo, and tumor height-to-width ratio. The discrimination performance of the nomogram was indicated by an area under the curve of 87.7%, and internal validation showed that the chi-square value of the Hosmer-Lemeshow test was 7.67 ( p = 0.363). Thus, the integrative prediction model using clinical data can predict the probability of pCR in patients with TNBC receiving NAC.

Background: Sentinel lymph node biopsy (SLNB) is the standard axillary staging approach for early breast cancer with clinically negative axillary involvement. Adequate SLNB should include the removal of not only radioactive tracer-labeled lymph nodes (hot nodes or SLNs) but also suspicious unlabeled nodes (non-hot nodes or non-SLNs). However, the biopsy of non-hot nodes is highly dependent on the surgeons' experiences. This article aims to facilitate the surgeon's decision making by elucidating parameters that correlate with non-hot node metastasis., Methods: From 2013 to 2016, clinically node-negative (cN0) breast cancer patients receiving axillary SLNB using single Tc-99m tracer method at our institute were recruited. Patients were excluded if they had received prior neoadjuvant chemotherapy. Among them, cases that have at least one non-isotope-hot node biopsied were retrospectively reviewed with a particular focus on patients with pathologically negative isotope-hot SLNs. The correlation of clinicopathological data with metastasis to axillary lymph nodes and sentinel lymph nodes was analyzed with the Chi-squared test, Fisher's exact test, and multivariate logistic regression. Receiver operating curve (ROC) was applied for continuous variables that predicted non-hot node metastasis; relapse-free survival (RFS) and locoregional relapse-free survival (LRRFS) were compared by Kaplan-Meier analysis., Results: In 632 isotope-hot SLN negative patients, T stage showed a correlation with non-isotope-hot SLN metastasis (p = 0.035, odds ratio (OR) 9.65). Tumors larger than 2.5 cm best predict non-isotope-hot SLN metastasis (area under curve (AUC) = 0.71). With a median follow up of 41.80 months, locoregional relapse-free survival was significantly worse in cases with non-hot node metastasis (66.2% vs. 69.0%, p = 0.001)., Conclusion: In the setting of SLNB using single radioisotope tracer, non-hot node metastasis in cases with negative hot SLN still carries a higher locoregional recurrence rate (13.3%). For early breast cancer larger than 2.5 cm, removal of suspicious non-hot nodes should be included for a precision therapy., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

We retrospectively enrolled 139 patients who developed metachronous isolated supraclavicular lymph node metastasis (miSLNM) from 8129 consecutive patients who underwent primary surgery between 1990 and 2008 at a single medical center. The median age was 47 years. The median follow-up time from date of primary tumor surgery was 73.1 months, and the median time to the date of neck relapse was 43.9 months in this study. Sixty-one (43.9%) patients underwent selective neck dissection (SND). The 5-year distant metastasis-free survival (DMFS), post-recurrence survival, and overall survival (OS) rates in the SND group were 31.1%, 40.3%, and 68.9%, respectively, whereas those of the no-SND group were 9.7%, 32.9%, and 57.7%, respectively ( p = 0.001). No SND and time interval from primary tumor surgery to neck relapse ≤24 months were the only significant risk factors in the multivariate analysis of DMFS (hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23-2.56; p = 0.002 and HR, 1.76, 95% CI, 1.23-2.52; p = 0.002, respectively) and OS (HR, 1.77; 95% CI, 1.22-2.55; p = 0.003 and HR, 3.54, 95% CI, 2.44-5.16; p < 0.0001, respectively). Multimodal therapy, including neck dissection, significantly improved the DMFS and OS of miSLNM. Survival improvement after miSLNM control by intensive surgical treatment suggests that miSLNM is not distant metastasis.

Background: The contrast-enhanced mammographic features of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) manifesting microcalcifications only on mammograms were evaluated to determine whether they could predict IDC underestimation., Methods: We reviewed patients who underwent mammography-guided biopsy on suspicious breast microcalcifications only and received contrast-enhanced spectral mammography (CESM) within 2 weeks before the biopsy. Those patients who were proven to have cancers (DCIS or IDC) by biopsy and subsequently had surgical treatment in our hospital were included for analysis. The presence or absence, size, morphology and texture of enhancement on contrast-enhanced spectral mammography were reviewed by consensus of two radiologists., Results: A total of 49 patients were included for analysis. Forty patients (81.6%) showed enhancement, including 18 (45%) DCIS and 22 (55%) IDC patients. All nine unenhanced cancers were pure DCIS. Pure DCIS showed 72.22% nonmass enhancement and 83.33% pure ground glass enhancement. IDC showed more mass (72.2% vs. 27.8%) and solid enhancements (83.33% vs. 16.67%). The cancer and texture of enhancement were significantly different between pure DCIS and IDC, with moderate diagnostic performance for the former ( p -value < 0.01, AUC = 0.66, sensitivity = 93%, specificity = 39%) and the latter ( p -value < 0.01, AUC = 0.74, sensitivity = 65%, specificity = 83%). Otherwise, pure DCIS showed a significant difference in enhanced texture compared with upgraded IDC and IDC ( p = 0.0226 and 0.0018, respectively)., Conclusions: Nonmass and pure ground glass enhancements were closely related to pure DCIS, and cases showing mass and unpurified solid enhancements should be suspected as IDC. Unenhanced DCIS with microcalcifications only has a low DCIS upgrade rate. The CESM-enhanced features could feasibly predict IDC underestimation.

Sentinel lymph node (SLN) biopsy (SLNB) usually need not be simultaneously performed with breast-conserving surgery (BCS) for patients diagnosed with ductal carcinoma in situ (DCIS) by preoperative core needle biopsy (CNB), but must be performed once there is invasive carcinoma (IC) found postoperatively. This study aimed to investigate the factors contributing to SLN metastasis in underestimated IC patients with an initial diagnosis of DCIS by CNB. We retrospectively reviewed 1240 consecutive cases of DCIS by image-guided CNB from January 2010 to December 2017 and identified 316 underestimated IC cases with SLNB. Data on clinical characteristics, radiologic features, and final pathological findings were examined. Twenty-three patients (7.3%) had SLN metastasis. Multivariate analysis indicated that an IC tumor size > 0.5 cm (odds ratio: 3.11, p = 0.033) and the presence of lymphovascular invasion (odds ratio: 32.85, p < 0.0001) were independent risk predictors of SLN metastasis. In the absence of any predictors, the incidence of positive SLNs was very low (2.6%) in the total population and extremely low (1.3%) in the BCS subgroup. Therefore, omitting SLNB may be an acceptable option for patients who initially underwent BCS without risk predictors on final pathological assessment. Further prospective studies are necessary before clinical application.

Few studies have analyzed the discrepancy between breast pathologic complete response (B-pCR) and axillary node pCR (N-pCR) rates and their impact on survival outcomes in different intrinsic subtypes of early breast cancer after neoadjuvant chemotherapy (NAC). We retrospectively reviewed B-pCR, N-pCR, and total (breast and axillary node) pCR (T-pCR) after NAC to assess the discrepancy and outcomes between 2005 and 2017. A total of 968 patients diagnosed with cT1-4c, N1-2, and M0 breast cancer were enrolled in the study. The median age was 49 years and the median follow-up time was 45 months. Of these patients, 213 achieved T-pCR, 31 achieved B-pCR with axillary node pathologic non-complete response (N-non pCR), 245 achieved N-pCR with breast pathologic non-complete response (B-non pCR), and 479 achieved total (breast and axillary node) pathologic non-complete response (T-non pCR) after NAC. The highest B-pCR and N-pCR rates were found in the hormone receptor-negative, human epidermal growth factor receptor 2-positive HR(-)HER2(+) subtype, while the lowest B-pCR rate was found in the HR(+)HER2(-) subtype. The N-pCR rate was correlated to the B-pCR rate (P<0.001), but was higher than the B-pCR rate in all subtypes. The 5-year overall survival (OS) rates for patients with T-pCR, B-pCR, and N-pCR were 91.2%, 91.7%, and 91.9%, respectively. For non-pCR, non-pCR, and non-pCR, the 5-year OS rates were 73.6%, 78.9%, and 74.7%, respectively (P<0.0001). B-non pCR patients had a lower risk of recurrence than T-non pCR or N-non-pCR patients, although there were no differences in OS among them. In conclusion, the N-pCR rate was higher than the B-pCR rate after NAC in all intrinsic subtypes, and N-non pCR or T-non pCR patients had the worst outcomes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Neoadjuvant chemotherapy (NACT) was initially applied to locally advanced breast cancer to convert advanced lesions to an operable status. Currently, its application has been expanded to enhance overall oncological results, especially in patients with triple-negative or HER-2-positive breast cancer. With more NACT being applied, the role and impact of this approach on breast reconstruction needs to be determined. This study aimed to perform a complete reconstructive outcome analysis of patients receiving NACT who underwent immediate breast reconstruction., Methods: A retrospective review of a single reconstructive surgeon's immediate breast reconstructions performed from July 2008 to December 2018 was undertaken. The results were stratified by the use of NACT. Patient demographics, delivery of NACT, adjuvant treatment, incidence of surgical complications, and postoperative photographs were analyzed., Results: A total of 269 patients were included. The mean follow-up was 46.3 months. Forty-six out of 269 patients received NACT and were included in the NACT group. The other patients were included in the non-NACT group. When implant-based reconstruction was planned, the NACT group had a higher rate of two-stage tissue expander-implant reconstruction than direct-to-implant reconstruction (p < 0.001). The requirement for postmastectomy radiotherapy was higher in the NACT group (p < 0.001). The surgical complication rates were similar between groups after adjusting for confounding factors. The objective aesthetic outcomes assessed by 6 plastic surgeons were also similar between groups., Conclusions: Immediate breast reconstruction is a safe and reliable procedure, with an acceptable reconstructive complication rate and satisfactory aesthetic outcomes, for patients treated with NACT.

Background: Neoadjuvant chemotherapy (NAC) has been the standard treatment for locally advanced breast cancer for the purpose of downstaging or for conversion from mastectomy to breast conservation surgery (BCS). Locoregional recurrence (LRR) rate is still high after NAC. The aim of this study was to determine predictive factors for LRR in breast cancer patients in association with the operation types after NAC., Methods: Between 2005 and 2017, 1047 breast cancer patients underwent BCS or mastectomy after NAC in Chang Gung Memorial Hospital, Linkou. We obtained data regarding patient and tumor characteristics, chemotherapy regimens, clinical tumor response, tumor subtypes and pathological complete response (pCR), type of surgery, and recurrence., Results: The median follow-up time was 59.2 months (range 3.13-186.75 months). The mean initial tumor size was 4.89 cm (SD ± 2.95 cm). Of the 1047 NAC patients, 232 (22.2%) achieved pCR. The BCS and mastectomy rates were 41.3% and 58.7%, respectively. One hundred four patients developed LRR (9.9%). Comparing between patients who underwent BCS and those who underwent mastectomy revealed no significant difference in the overall LRR rate of the two groups, 8.8% in BCS group vs 10.7% in mastectomy group (p = 0.303). Multivariate analysis indicated that independent factors for the prediction of LRR included clinical N2 status, negative estrogen receptor (ER), and failure to achieve pCR. In subgroups of multivariate analysis, only negative ER was the independent factor to predict LRR in mastectomy group (p = 0.025) and hormone receptor negative/human epidermal growth factor receptor 2 positive (HR-/HER2 +) subtype (p = 0.006) was an independent factor to predict LRR in BCS patients. Further investigation according to the molecular subtype showed that following BCS, non-pCR group had significantly increased LRR compared with the pCR group, in HR-/HER2 + subtype (25.0% vs 8.3%, p = 0.037), and HR-/HER2- subtype (20.4% vs 0%, p = 0.002)., Conclusion: Clinical N2 status, negative ER, and failure to achieve pCR after NAC were independently related to the risk of developing LRR. Operation type did not impact on the LRR. In addition, the LRR rate was higher in non-pCR hormone receptor-negative patients undergoing BCS comparing with pCR patients.

Objective: Stereotactic vacuum-assisted breast biopsy (VABB) is considered a reliable alternative to surgical biopsy for suspicious calcifications. In most cases, the management of flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) after VABB with residual calcifications requires surgical excision. This study aimed to evaluate the impact of pathology of non-calcified specimens on the underestimation of malignancy., Materials and Methods: We retrospectively reviewed 1147 consecutive cases of stereotactic VABB of suspicious calcifications without mass from January 2010 to December 2016 and identified 46 (4.0%) FEA and 52 (4.5%) ADH cases that were surgically excised for the retrieval of residual calcifications. Mammographic features and pathology of the calcified and non-calcified specimens were reviewed., Results: Seventeen specimens (17.3%) were upgraded to malignancy. Mammographic features associated with the underestimation of malignancy were calcification extent (> 34.5 mm: odds ratio = 6.059, p = 0.026). According to the pathology of calcified versus non-calcified specimens, four risk groups were identified: Group A (ADH vs. high-risk lesions), Group B (ADH vs. non-high-risk lesions), Group C (FEA vs. high-risk lesions), and Group D (FEA vs. non-high-risk lesions). The lowest underestimation rate was observed in Group D (Group A vs. Group B vs. Group C vs. Group D: 35.0% vs. 20.0% vs. 15.0% vs. 3.6%, p = 0.041, respectively)., Conclusion: Considering that the calcification extent and pathology of non-calcified specimens may be beneficial in determining the likelihood of malignancy underestimation, excision after FEA or ADH diagnosis by VABB is required, except for the diagnoses of FEA coexisting without atypia lesions in non-calcified specimens., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 The Korean Society of Radiology.)

The mammographic appearance of ductal carcinoma in situ (DCIS) is mostly observed as microcalcifications. Although stereotactic vacuum-assisted breast biopsy (VABB) is a reliable alternative to surgical biopsy for suspicious microcalcifications, underestimation of VABB-proven DCIS is inevitable in clinical practice. We therefore retrospectively analyzed the variables in the prediction of DCIS underestimation manifesting as microcalcifications only proved by stereotactic VABB. In 1147 consecutive VABB on microcalcification-only lesions from 2010 to 2016, patients diagnosed with DCIS were selected to evaluate the underestimation rate. The analyzed variables included clinical characteristics, mammographic features, VABB procedure, and biomarkers. Univariate and multivariate analyses were used, and a p value < 0.05 was considered statistically significant. Of the 131 VABB-proven DCIS, 108 cases were diagnosed with DCIS and 23 were upgraded to invasive ductal carcinoma (IDC) after subsequent surgery. The small extent of microcalcification, grouped microcalcifications distribution, nearly complete microcalcification removal, and non-calcified specimens without DCIS were low for DCIS underestimation. Among them, the results of non-calcified specimens with or without DICS were the only statistically significant variables by multivariate logistic regression. These results indicate that the histology of non-calcified specimens was highly predictive of DCIS underestimation. Specimens without DCIS had a low upgrade rate to IDC.

Background: This study aimed to identify the factors that predict distant recurrence and survival outcome after patients with primary positive hormone receptor-positive (HR+) invasive breast cancer undergo complete excision for isolated local recurrence (ILR)., Methods: From January 2000 to December 2009, we performed a retrospective review of our database and identified 51 patients with HR + invasive breast cancer who underwent complete excision for ILR as a component of salvage therapy. The distant metastasis-free survival (DMFS) and overall survival (OS) from the time of ILR were calculated using the Kaplan-Meier method, and a Cox regression model was used for multivariate analysis., Results: Of the 51 cases of ILR, 28 were of ipsilateral breast tumor recurrence and 23 were of chest wall recurrence. By receiver operating characteristic curve analyses, the cut-off time point for time to ILR was determined to be 29 months. According to time to ILR (≤29 vs. >29 months) and primary tumor size (≤2 vs. >2 cm), patients were divided into four risk groups as variables for analysis. On multivariate analysis, two independent prognostic factors for DMFS and OS after ILR were identified: risk groups (ILR≤29 months with primary tumor size >2 cm vs. ILR>29 months with primary tumor size ≤ 2 cm, HR = 8.53 for DMFS and HR = 11.18 for OS) and primary tumor grade (2/3 vs. 1, HR = 6.10 for DMFS and 4.27 for OS)., Conclusion: We demonstrated that poor DMFS and OS are associated with high risk group defined as short time to ILR (≤29 months) with primary tumor size (>2 cm) and higher primary tumor grade (2/3) among patients with HR + invasive breast cancer treated with complete excision for ILR. Therapeutic strategies for ILR based on hormone therapy with new agents should be explored in future prospective studies, especially for patients with poor outcome., (Copyright © 2019 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Neoadjuvant chemotherapy (NAC) is the standard approach for downstaging of locally advanced breast cancer and can improve breast conservation rates. A pathological complete response (pCR) after NAC associated with favorable long-term outcomes has been described. There is still a high locoregional recurrence (LRR) rate after NAC and the influence of age on LRR after NAC is unclear. This study analyzed the relationship between age and LRR after NAC., Methods: Two hundred and sixty-three patients with invasive breast cancer who received NAC followed by mastectomy or breast conserving surgery (BCS) were enrolled. Concurrent weekly epirubicin and docetaxel was the NAC regimen., Results: Twenty-nine patients (11%) achieved a pCR after NAC. In univariate analysis, age <50 years, luminal B (HER2 positive) subtype, HER2 overexpression subtype, and triple-negative subtype were factors to predict a pCR. In multivariate analysis, age <50 years, luminal B (HER2 positive) type, HER2 overexpression, and triple-negative subtype were the independent factors to predict a pCR. No patients in the pCR group developed LRR compared with 31 patients in the non-pCR group. Eleven patients (6.9%) in the younger group (age <50 years) developed LRR compared with 20 patients (19.4%) in the older group (age ≥50 years). In multivariate analysis, younger age (<50 years) was the only independent prognostic factor for a LRR-free survival., Conclusion: Younger age can predict a pCR and is an independent prognostic factor for LRR in locally advanced breast cancer patients after NAC as concurrent epirubicin and docetaxel., (Copyright © 2019 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Purpose: Breast conservation therapy (BCT) is widely accepted for breast cancer treatment. Nipple-sparing mastectomy has been newly developed to preserve the nipple-areolar complex and enhance aesthetic results. The purpose of this study was to evaluate the oncological safety and results of nipple-sparing mastectomy (NSM) after previous BCT., Methods: Eighteen patients who received NSM and immediate breast reconstruction for local recurrence after BCT were identified. An additional 127 affected breasts with NSM and immediate breast reconstruction for primary breast cancer were selected as the control group. The patient disease status, reconstructive method, postoperative complications, and oncological outcome were investigated., Results: No apparent significant differences between the 2 groups were found regarding patient demographic data, tumor stage, reconstructive method, surgical complication, or tumor recurrence rate (all P values >0.05), except preoperative radiotherapy was higher in secondary NSM group (0% vs 77.8%, P < 0.001). The further nipple and secondary deep inferior epigastric artery perforator flap reconstruction rate was higher in the secondary NSM group (11.1% vs 0.8%, P = 0.041 and 16.7% vs 2.4%, P = 0.026, respectively)., Conclusions: Prior BCT did not contribute to higher surgical complications in patients who received NSM and immediate reconstruction as a salvage procedure after tumor local recurrence. The oncological safety, general surgical result, and postoperative patient-reported satisfaction remain safe and reliable despite prior ipsilateral surgery and radiation. Care should be taken for possible higher nipple necrosis in the secondary NSM patients.

The research of carcinogenetic mechanisms of breast cancer in different ethnic backgrounds is an interesting field, as clinical features of breast cancers vary among races. High premenopausal incidence is distinctive in East-Asian breast cancer. However, human cell lines derived from Asian primary breast tumor are rare. To provide alternative cell line models with a relevant genetic background, we aimed to establish breast cancer cell lines from Taiwanese patients of Han-Chinese ethnicity. Fresh tissue from mammary tumors were digested into organoids, plated and grown in basal serum-free medium of human mammary epithelial cells (HuMEC) with supplements. Cells were further enriched by positive selection with CD326 (epithelial cell adhesion molecule; EpCAM)-coated micro-magnetic beads. Two breast cancer cell lines derived from premenopausal women were successfully established by this method, and named Chang-Gung Breast Cancer 01 (CGBC 01) and 02 (CGBC 02). These two cell lines had a similar phenotype with weak expression of estrogen receptor (ER), progesterone receptor (PR), and without amplification of receptor tyrosine protein kinase erbB-2 (HER2/neu). Genome-wide Single Nucleotide Polymorphism (SNP) array showed multiple copy number alterations in both cell lines. Based on gene expression profiles, CGBC 01 and 02 were clustered into basal-like subtype with reference to the breast cancer cell line gene expression database. The tumorigenicity of both cell lines was extremely low in both anchorage-independence assay and transplantation into the mammary fat pads of nude mice. CGBC 01 and CGBC 02 are low tumorigenic breast cancer cell lines, established from Han-Chinese premenopausal breast cancer patients, which serve as in vitro models in studying the biological features of Asian breast cancer.

Background: T1a,bN0 breast cancer is not easily detected. Before mammography became widespread, most cases were discovered only after the development of symptoms. The presence of ductal carcinoma in situ (DCIS) affects the detectability of associated invasive cancer; however, the prognostic value of concomitant DCIS is controversial. This study compared the characteristics of screening-detected and symptom-detected T1a,bN0 breast cancer, and investigated the impact of accompanying DCIS on detection and prognosis. Patients and Methods: Data were collected from a single hospital between 2000 and 2009. Of 5,690 primary breast cancers patients, 438 met the criteria for T1a,bN0M0. Logistic regression models were used to identify prognostic indicators and their association with the detection method. Survival analyses were performed to estimate distant relapse-free survival (DRFS) and breast cancer-specific survival (BCSS). Results: Tumors in 79 and 359 patients were detected by screening and development of symptoms, respectively. Symptomatic cancer patients were younger, more likely to receive a mastectomy, and had larger accompanying DCIS lesions; their 10-year DRFS rates were worse than those of patients with screening-detected tumors (91.1% vs. 100% respectively, p =0.049). Patients with large accompanying DCIS (≥2 cm) had markedly worse 10-year DRFS (77.1% vs. 97.4%, p <0.001) and BCSS (94.3% vs. 98.9%, p <0.001). Conclusion: T1a,bN0 breast cancers detected owing to symptoms are more likely to have larger accompanying DCIS. T1a,bN0 patients with large accompanying DCIS have worse DRFS and BCSS. It is important to consider associated DCIS size when evaluating prognosis in T1a,bN0 breast cancer patients., Competing Interests: Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have declared that no competing interests exist.

Purpose: Exploration of the internal mammary vessels during microsurgical reconstruction presents an ideal opportunity for identifying and sampling the internal mammary lymph node (IMLN) basin., Methods: A retrospective review of patients undergoing microsurgical breast reconstruction using the internal mammary vessels as recipient vessels was conducted from March 2000 to December 2014. Patient demographics, tumor characteristics, preoperative lymph node mapping, reconstructive timing, and outcomes were studied., Results: A total of 524 microsurgical breast reconstructions in 516 patients were performed using the internal mammary vessels. IMLNs were sampled in 53 immediate and 42 delayed breast reconstructions. Eight (seven in the immediate and one in the delayed group) of the sampled nodes were positive for cancer metastasis, for an incidence of 8.4% in identified lymph nodes. All patients with metastatic IMLNs subsequently received local-regional radiation and chemotherapy. All patients were alive, and six were disease-free at the conclusion of the study period, which had an average follow up of 67.3 months., Conclusion: Incidentally encountered IMLNs during microsurgical breast reconstruction are frequently positive. With negligible downside and the possibility to provide additional information for treatment, the procedure should be encouraged. J. Surg. Oncol. 2016;114:133-139. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are precursors of breast malignancy. Management of FEA or ADH after image-guided core needle biopsy (CNB) remains controversial. The aim of this study was to evaluate malignancy underestimation rates after FEA or ADH diagnosis using image-guided CNB and to identify clinical characteristics and imaging features associated with malignancy as well as identify cases with low underestimation rates that may be treatable by observation only. We retrospectively reviewed 2,875 consecutive image-guided CNBs recorded in an electronic data base from January 2010 to December 2011 and identified 128 (4.5%) FEA and 83 (2.9%) ADH diagnoses (211 total cases). Of these, 64 (30.3%) were echo-guided CNB procedures and 147 (69.7%) mammography-guided CNBs. Twenty patients (9.5%) were upgraded to malignancy. Multivariate analysis indicated that age (OR = 1.123, p = 0.002, increase of 1 year), mass-type lesion with calcifications (OR = 8.213, p = 0.006), and ADH in CNB specimens (OR = 8.071, p = 0.003) were independent predictors of underestimation. In univariate analysis of echo-guided CNB (n = 64), mass with calcifications had the highest underestimation rate (p < 0.001). Multivariate analysis of 147 mammography-guided CNBs revealed that age (OR = 1.122, p = 0.040, increase of 1 year) and calcification distribution were significant independent predictors of underestimation. No FEA case in which, complete calcification retrieval was recorded after CNB was upgraded to malignancy. Older age at diagnosis on image-guided CNB was a predictor of malignancy underestimation. Mass with calcifications was more likely to be associated with malignancy, and in cases presenting as calcifications only, segmental distribution or linear shapes were significantly associated with upgrading. Excision after FEA or ADH diagnosis by image-guided CNB is warranted except for FEA diagnosed using mammography-guided CNB with complete calcification retrieval., (© 2015 Wiley Periodicals, Inc.)

Background: Re-excision is a necessary procedure in obtaining clean margins for breast-conserving surgery (BCS)-treated patients. Re-excision rates vary widely among different breast cancer management procedures. The aim of this study was to evaluate the efficacy of ultrasound (US)-guided BCS to decrease the re-excision rate in patients with US-detectable breast cancer, as well as the relationship between positive margins and ultrasonographic characteristics of tumor., Methods: Between 2008 and 2009, we identified consecutive patients who underwent initial US-guided BCS for breast in situ or invasive carcinoma, which was preoperatively detected using US examination and on the basis of image-guided biopsy findings. The margins achieved after BCS were separately assessed by performing frozen section analysis of shaved margins. The negative margin and positive margin groups were compared for clinicopathological features and ultrasonographic findings., Results: Of 381 patients undergoing US-guided BCS, 126 (33.1%) had palpable tumors and 255 (66.9%) had nonpalpable tumors. Positive margins were noted in 35 patients (9.2%). These patients underwent re-excision and were margin-free; no further surgery was required for these patients. There were no significant intergroup differences in clinicopathological features and ultrasonographic findings., Conclusion: Breast US is an effective modality for intraoperative tumor localization and can thus help obtain clean margins and reduce the re-excision rate in cases in which breast-conserving therapy has been performed. Furthermore, frozen section analysis of cavity shaved margins is a feasible method for minimizing the need for further surgery., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.

Purpose: Little evidence can be found about the long-term outcome of breast cancer patients after axillary lymph node recurrence (ALNR) and its survival benefit after different kinds of management. The present study intends to evaluate the risk factors associated with axillary recurrence after definite surgery for primary breast cancer. The prognosis after ALNR and particularly outcome of different management methods also were studied., Methods: We retrospectively reviewed data from 4,473 patients who were diagnosed with primary breast cancer and received surgical intervention in a single institute from January 1990 to December 2002. Medical files were reviewed and data on survival were updated annually. Risk factors and prognosis of patients with axillary recurrence were analyzed. Breast-cancer-specific survival of patients with ALNR and outcomes after different management methods also were studied., Results: After a median follow-up of 70.2 months, axillary recurrence developed in 0.8% of patients. Factors associated with ALNR included: age younger than 40 years, medial tumor location, no initial standard level I & II axillary dissection, and not receiving hormonal therapy. The 5-year breast-cancer-specific survival after ALNR was 57.9%. For patients who received further axillary dissection, the 5-year survival rate was 82.5% compared with 44.9% for patients who did not receive further dissection., Conclusions: ALNR is a rare event in treating breast cancer. Young age at diagnosis and medially located tumor are associated with higher risk, but standardized initial axillary dissection to level II and adjuvant hormonal therapy is protective against ALNR. In patients with ALNR, the outcome is not dismal and survival may be improved if further axillary dissection is given.

Aim: To report the clinicopathological features and magnetic resonance imaging (MRI) findings of solid and pseudopapillary tumor (SPT) of pancreas., Methods: From 1981 to 2005, 26 surgically treated cases of SPT were retrospectively reviewed. MRI findings of the latest 11 consecutive SPT cases were investigated., Results: There were 25 women and one man having SPT (median age: 23 year) with a median tumor size of 7.5 cm. Among them, nine patients developed solid pseudopapillary carcinoma. During the median follow-up period of 66 mo, the 5-year survival rate of the 26 SPT patients was 96.2%. Three MRI features were proposed including Type 1 image, displaying SPT with completely solid part. All SPT patients with type 1 image were detected incidentally. Type 2 image displays of SPT with solid mass hemorrhage and type 3 image with massive hemorrhage. All the eight SPT patients with type 2 and 3 images suffered abdominal pain due to hemorrhage from SPT., Conclusion: SPT had a favorable survival rate irrespective of surgical procedures, malignancy, and MRI findings, however, MRI could reliably correlate with its clinicopathological features.