Yao Lung Kuo

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

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

Breast cancer arising within fibroadenoma: collective analysis of case reports in the literature and hints on treatment policy

BackgroundBreast cancer arising within a fibroadenoma (BcaFad) is rare; the rate varies from 0.002% to 0.125% in fibroadenoma specimens. Owing to its rarity, the clinicopathologic feature and treatment principle of BcaFad is still not clear. Therefore, the aim of this study was to perform a collective analysis of case reports in the literature to identify the characteristics and optimal treatment for BcaFad.MethodsWe analyzed an aggregated sample of 30 patients with BcaFad from case reports in the literature (n =24 cases) and our present study (n =6 cases). We collected and analyzed the clinicopathologic features and prognoses of patients with BcaFad, as well as treatments they received.ResultsThe patients’ mean age at diagnosis was 46.9xa0years. Twenty BcaFad patients (66.7%) received breast-conserving surgery (BCS), and nine other patients (30.0%) were treated with mastectomy. The rate of lymph node metastasis in BcaFad patients was 23.8%. The breakdown of the histological types of BcaFad was invasive ductal carcinoma (53.3%), followed by ductal carcinoma in situ (23.3%), lobular carcinoma in situ (16.7%) and invasive lobular carcinoma (13.3%). More than half of patients with positive hormone receptor status received hormone therapy. Most BcaFad patients with lymph node metastases received chemotherapy, and 20.0% of BcaFad patients treated with BCS received further radiotherapy. Only one patient had recurrence after surgery, and another had lung metastasis when diagnosed with BcaFad.ConclusionsMost BcaFad patients could be managed by BCS. Adjuvant radiotherapy could be performed, but was not mandatory. Chemotherapy should be considered as a treatment option in the presence of lymph node metastasis.

Current Trends in and Indications for Endoscopy-Assisted Breast Surgery for Breast Cancer: Results from a Six-Year Study Conducted by the Taiwan Endoscopic Breast Surgery Cooperative Group

Background Endoscopy-assisted breast surgery (EABS) performed through minimal axillary and/or periareolar incisions is a possible alternative to open surgery for certain patients with breast cancer. In this study, we report the early results of an EABS program in Taiwan. Methods The medical records of patients who underwent EABS for breast cancer during the period May 2009 to December 2014 were collected from the Taiwan Endoscopic Breast Surgery Cooperative Group database. Data on clinicopathologic characteristics, type of surgery, method of breast reconstruction, complications and recurrence were analyzed to determine the effectiveness and oncologic safety of EABS in Taiwan. Results A total of 315 EABS procedures were performed in 292 patients with breast cancer, including 23 (7.8%) patients with bilateral disease. The number of breast cancer patients who underwent EABS increased initially from 2009 to 2012 and then stabilized during the period 2012–2014. The most commonly performed EABS was endoscopy-assisted total mastectomy (EATM) (85.4%) followed by endoscopy-assisted partial mastectomy (EAPM) (14.6%). Approximately 74% of the EATM procedures involved breast reconstruction, with the most common types of reconstruction being implant insertion and autologous pedicled TRAM flap surgery. During the six-year study period, there was an increasing trend in the performance of EABS for the management of breast cancer when total mastectomy was indicated. The positive surgical margin rate was 1.9%. Overall, the rate of complications associated with EABS was 15.2% and all were minor and wound-related. During a median follow-up of 26.8 (3.3–68.6) months, there were 3 (1%) cases of local recurrence, 1 (0.3%) case of distant metastasis and 1 (0.3%) death. Conclusion The preliminary results from the EABS program in Taiwan show that EABS is a safe procedure and results in acceptable cosmetic outcome. These findings could help to promote this under-used surgical technique in the field of breast cancer.

Endoscopy-Assisted Total Mastectomy Followed by Immediate Pedicled Transverse Rectus Abdominis Musculocutaneous (TRAM) Flap Reconstruction: Preliminary Results of 48 Patients

Background. Endoscopy-assisted breast surgery performed through minimal axillary and/or periareolar incisions is a viable option for patients with breast cancer. In this study, we report the preliminary results of patients with breast cancer who underwent endoscopy-assisted total mastectomy (EATM) followed immediately by pedicled transverse abdominis musculocutaneous (TRAM) flap reconstruction. Methods. Patients in this study comprised women with breast cancer who received EATM and pedicled TRAM flap reconstruction. Clinicopathologic characteristics, type of surgery, complications, and rate of recurrence were recorded. The cosmetic outcomes were evaluated objectively by the surgeons and subjectively by the patients at 3-month postoperative follow-up. Results. A total of 48 patients underwent 49 EATM procedures followed by pedicled TRAM flap reconstruction. Of them, 79.6% underwent endoscopic-assisted nipple-sparing mastectomy and 20.4% received endoscopic-assisted skin-sparing mastectomy. The types of cancer among these patients included ductal carcinoma in situ in 34.7%, stage I cancer in 36.7%, stage II cancer in 24.5%, and stage IIIa cancer in 4.1% patients. Mean tumor size was 2.1 ± 1.4 cm. There were no cases of flap failure. Partial nipple areolar complex ischemia/necrosis occurred in 4 (10.3%) patients; however, all cases resolved after conservative treatment. In the aesthetic outcome evaluation, EATM + TRAM were associated with 89.8% good, 8.2% fair, and 2% unsatisfactory result. No local recurrence was observed during the follow-up period. Conclusion. EATM followed immediately by pedicled TRAM flap reconstruction is a safe procedure and results in good cosmetic outcome in women with early-stage breast cancer.

Validation of Memorial Sloan-Kettering Cancer Center nomogram for prediction of non-sentinel lymph node metastasis in sentinel lymph node positive breast cancer patients an international comparison.

BACKGROUNDnCurrent guidelines for breast cancer treatment recommend completion axillary lymph node dissection (CALND) following in case of positive sentinel lymph node (SLN) metastasis, which only in 35%-70% shows additional nodal metastases. Several nomograms and scoring systems have been created to predict the risk of metastasis in non-SLNs. The aim of the study was to identify individual patient risk for non-sentinel lymph node metastasis by validating with MSKCC nomogram and to evaluate the variability within a group of SLN-positive breast cancer patients with the final goal of avoiding unnecessary CALND.nnnPATIENTS AND METHODSnWe retrospectively evaluated 1496 primary breast cancer patients. 324 women with a positive SLN who underwent CALND were identified. The predictive accuracy was measured and compared with the MSKCC nomogram by the area under the receiver operating characteristic curve. Receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity, and the area under the curve (AUC) was calculated.nnnRESULTSnAt least one metastatic non-SLN were identified in 88/324 (27.2%) patients. Tumor size, tumor type, tumor grade, number of positive SLNs and number of negative SLNs were significantly associated with non-SLN status in multivariate analyses. The MSKCC nomogram showed an AUC value of 0.738 (95% confidence intervalxa0=xa00.682-0.793) after the validation for our collectives.nnnCONCLUSIONSnThe MSKCC nomogram showed a good prediction for the non-SLN metastasis and performed adequately in our patient collective. Therefore, for the use of nomogram, validation with other populations of patients is strongly suggested.

HDAC2 and HDAC5 up-regulations modulate survivin and miR-125a-5p expressions and promote hormone therapy resistance in estrogen receptor positive breast cancer cells

Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+) breast cancer patients. Even though dysregulations of histone deacetylases (HDACs) are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan–Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.

miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer

BackgroundTriple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted therapeutics. Moreover, chemotherapy only produces 20–30% pathologic complete response. Because miRNAs are frequently dysregulated in breast cancer and have broad tissue effects, individual or combinations of circulating miRNAs may serve as ideal diagnostic, predictive or prognostic biomarkers, as well as therapeutic targets. Understanding the role and mechanism of dysregulated miRNAs in TNBC may help to develop novel diagnostic and prognostic strategy for TNBC patients.MethodsThe miRNA array profiles of 1299 breast cancer patients were collected from the Metabric database and subjected to analysis of the altered miRNAs between TNBC and non-TNBC. In Student’s t-test and Kaplan-Meier analysis, four upregulated miRNAs correlated with poor survival in TNBC but not in non-TNBC. Four miRNAs were manipulated in multiple cell lines to investigate their functional role in carcinogenesis. From these results, we studied miR-105 and miR-93-3p in greater detail. The level of miR-105 and miR-93-3p were evaluated in 25 breast cancer tumor tissues. In addition, the diagnostic utility of circulating miR-105 and miR-93-3p were examined in 12 normal and 118 breast cancer plasma samples by ROC curve construction.ResultsmiR-105 and miR-93-3p were upregulated and correlated with poor survival in TNBC patients. Both miR-105 and miR-93-3p were found to activate Wnt/β-catenin signaling by downregulation of SFPR1. By this action, stemness, chemoresistance, and metastasis were promoted. Importantly, thexa0combination of circulating miR-105/93-3p may serve as a powerful biomarker for TNBC, even in early-stage disease.ConclusionsmiR-105/93-3p activates Wnt/β-catenin signaling by downregulating SFRP1 and thereby promotes stemness, chemoresistance, and metastasis in TNBC cells. Most importantly, combined circulating miR-105/93-3p levels represent a prime candidate for development into a diagnostic biomarker for both early- and late-stage TNBC.

Which hottest nodes can predict sentinel lymph node metastasis in breast cancer

BACKGROUNDnIn approximately 80% of breast cancer patients, the hottest sentinel lymph nodes (SLNs) can be used to predict nodal metastasis. We correlate the reliability of using these nodes to predict SLN metastasis with different lymphoscintigraphic patterns in breast cancer.nnnMETHODSnSLN biopsies for T(1-2)N(o) breast cancer were performed on 467 patients. Lymphoscintigraphic patterns were divided into three groups by the number of draining routes using blue dye and radiocolloid and whether the hottest nodes were the first nodes in the channel.nnnRESULTSnThe hottest SLNs detected 78 of 87 (90%) cases of SLN metastasis in the 399 patients with successful labeling of both blue dye and radiocolloid in their SLNs. False-negative rates were 0% (single-channel, first node), 58% (multi-channel, first node), and 71% (zero-channel, 0 hottest nodes) (FNR: SingleChanl versus ZeroChanl, P=0.005 and SingleChanl versus MultiChanl, P=0.037; Fishers exact test).nnnCONCLUSIONSnWe recommend a preoperative lymphoscintigram to distinguish the subset of breast-cancer patients with a single draining channel and whose hottest node is the first node.

The learning curve of endoscopic total mastectomy in Taiwan: A multi-center study

Introduction Laparoscopic techniques are commonly used in abdominal and gynecologic surgery, while breast cancer surgery has remained largely unchanged. In Asia, especially in Japan, many surgeons have started to use endoscopic surgery for breast cancer. In Taiwan, endoscopy-assisted breast surgery started in 2010. The benefits of this surgical method include smaller incisions, an axillary anatomic approach, clear vision, no oncologic compromise, and good cosmetic outcomes. This is the first report to discuss the learning curve of endoscopy-assisted breast surgery, including the difficulties experienced. Materials and methods From June 2011 to December 2013, data were collected from 134 patients who received an endoscopic total mastectomy at the Taipei Medical University Hospital (TMUH) or Changhua Christian Hospital (CCH). We divided these patients into a learning group (TMUH, n = 15; CCH, n = 15) and a mature group (TMUH, n = 50; CCH, n = 54). Patient data and perioperative variables were recorded by retrospective chart review. Variables were compared using the χ2 test and Student’s t-test. Results There was a significant difference in operation time (275.3 vs. 228.9 minutes, p < 0.01) between the learning and mature groups. Perioperative variables (lymph node dissection method, nipple preservation, and reconstruction method) were also analyzed, but there were no demographic differences between the groups. The complication rate was higher in the learning group, although this difference was also not statistically significant. Conclusion Our study is the first to discuss the learning curve of endoscopic total mastectomy. The operation time decreased significantly after 15 cases at each hospital. Although the operation is still more time-consuming than traditional methods, it has the benefit of smaller wounds and improved cosmetic outcomes if combined with immediate reconstruction.

Round block technique is a useful oncoplastic procedure for multicentric fibroadenomas

PURPOSEnMulticentric fibroadenomas, defined as multiple fibroadenomas located at different quadrants of the breast, occur in 10-20% of women with fibroadenoma. The surgical management of multicentric fibroadenomas may be troublesome for surgeons and patients. In this study, we report our preliminary experience using the round block technique in the management of women with multicentric fibroadenomas of the breast.nnnMATERIALS AND METHODSnRecords of patients with breast diseases managed with the round block technique were searched for in the Changhua Christian Hospital oncoplastic breast surgery database. The patients clinicopathologic characteristics, type of surgery, operation time, blood loss, and complications were recorded. The cosmetic outcome was evaluated by the patient and operating surgeon two months after the surgery.nnnRESULTSnTwenty patients with multicentric fibroadenomas managed by the round block technique comprised the current study cohort. The mean age of the subjects was 36.5xa0±xa010.4 years. Twelve (60%) patients had tumors on one side of the breast, and eight (40%) had bilateral breast lesions. The average number of tumors removed was 3.3xa0±xa01.2 (range 2-6) per breast, and mean tumor size was 2.2xa0±xa00.5xa0cm. Three (15%) patients developed mild ecchymosis of the breast undergoing operation, which resolved spontaneously. One (5%) patient had partial nipple ischemia/necrosis due to 2 tumors excised near the nipple-areolar complex. The aesthetic results were evaluated as good in 19 (95%) patients and fair in 1 (5%).nnnCONCLUSIONSnThe round block technique is a useful oncoplastic procedure for the management of multicentric fibroadenomas excised at the same time.