Robotic Versus Conventional or Endoscopic-assisted Nipple-sparing Mastectomy and Immediate Prosthesis Breast Reconstruction in the Management of Breast Cancer: A Prospectively Designed Multicenter Trial Comparing Clinical Outcomes, Medical Cost, and Patient-reported Outcomes (RCENSM-P).

OBJECTIVE: To compare the clinical and patient-reported outcomes of minimal access and conventional nipple-sparing mastectomy (C-NSM). The secondary outcomes investigated included medical costs and oncological safety. BACKGROUND: Minimal-access NSM has been increasingly applied in the treatment of patients with breast cancer. However, prospective multicenter trials comparing robotic-assisted NSM (R-NSM) versus C-NSM or endoscopic-assisted NSM (E-NSM) are lacking. METHODS: A prospectively designed 3-arm multicenter, nonrandomized trial (NCT04037852) was conducted from October 1, 2019 to December 31, 2021, to compare R-NSM with C-NSM or E-NSM. RESULTS: A total of 73 R-NSM, 74 C-NSM, and 84 E-NSM procedures were enrolled. The median wound length and operation time of C-NSM was (9 cm, 175 minutes), (4 cm, and 195 minutes) in R-NSM, and (4 cm and 222 minutes) in E-NSM. Complications were comparable among the groups. Better wound healing was observed in the minimal-access NSM group. The R-NSM procedure was 4000 and 2600 United States Dollars more expensive than C-NSM and E-NSM, respectively. Wound/scar and postoperative acute pain evaluation favored the use of minimal access NSM over C-NSM. Quality of life in terms of chronic breast/chest pain, mobility, and range of motion of the upper extremity showed no significant differences. The preliminary oncologic results showed no differences among the 3 groups. CONCLUSIONS: R-NSM or E-NSM is a safe alternative if compared with C-NSM in terms of perioperative morbidities, especially with better wound healing. The advantage of minimal access groups was higher wound-related satisfaction. Higher costs remain one of the major limiting factors in the widespread adoption of R-NSM.

Reliability of predicting low-burden (≤ 2) positive axillary lymph nodes indicating sentinel lymph node biopsy in primary operable breast cancer - a retrospective comparative study with PET/CT and breast MRI.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden. METHODS: A total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance. RESULTS: PET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1-2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0-2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone. CONCLUSIONS: PET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging.

Radiotherapy versus low-dose tamoxifen following breast-conserving surgery for low-risk and estrogen receptor-positive breast ductal carcinoma in situ: an international open-label randomized non-inferiority trial (TBCC-ARO DCIS Trial).

BACKGROUND: Radiotherapy (RT) following breast-conserving surgery (BCS) is mainly used to decrease the rate of ipsilateral breast tumor recurrence (IBTR) in women with breast ductal carcinoma in situ (DCIS). Recent studies have demonstrated that low-dose tamoxifen significantly reduces IBTR in breast DCIS. Here, we aim to determine whether the administration of low-dose tamoxifen is non-inferior to RT in preventing IBTR in patients with low-risk characteristics of breast DCIS. METHODS/DESIGN: This is a prospective, international, open-label, randomized, non-inferiority trial. Patients with low-risk clinicopathologic features (> 40 years old, low risk of breast cancer susceptibility gene (BRCA) 1 and BRCA2 mutations, mammographically detected unicentric and non-mass lesions, low- or intermediate-grade without comedo or necrosis, measuring < 2.5 cm with margins ≥ 3 mm, and estrogen receptor-positive status) of DCIS who underwent BCS will be randomized at a 1:1 ratio to either receive tamoxifen (5 mg/day) for 5 years or undergo RT with conventional fractions (50 Gy in 25 fractions) or hypofractionations (40.05 Gy in 15 fractions). Randomization will be stratified by the Taiwan Breast Cancer Consortium. As approximately 5% of patients cannot tolerate the side effects of low-dose tamoxifen and will receive RT, we estimate that 405 patients will be randomized to a low-dose tamoxifen arm and 405 patients to the RT arm, according to a non-inferiority margin within 5% of IBTR difference and 90% ß-power noticing non-inferiority. The primary endpoints are breast tumor recurrence, including ipsilateral, regional, contralateral, and distant recurrence of breast DCIS or invasive cancer. The secondary endpoints are overall survival and adverse effects of RT and tamoxifen. Translational studies will also be conducted for this trial. DISCUSSION: This is the first non-inferiority trial on breast DCIS. This study will provide an important recommendation for clinical physicians on whether to use low-dose adjuvant tamoxifen for patients with low-risk breast DCIS who do not want to receive adjuvant RT. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT04046159, Registered on April 30, 2019.

Single-port three-dimensional (3D) endoscopic-assisted breast surgery-preliminary results and patient-reported satisfaction in 145 breast cancer and gynecomastia cases.

BACKGROUND: Minimal-accessed (robotic and endoscopic) breast cancer surgery is increasingly performed due to better cosmetic results and acceptable oncological outcomes. This study aims to demonstrate the clinical safety and patient-reported cosmetic satisfaction of single-port three-dimensional endoscopic-assisted breast surgery (S-P 3D EABS), which is our new endoscopic surgical innovation, in both malignant and benign breast conditions. METHODS: Patients who underwent S-P 3D EABS from 1 August 2018 to 31 July 2022 in a single institution were enrolled. Clinical outcomes of this procedure were retrospectively reviewed, and the patient-reported cosmetic satisfaction was evaluated by a questionnaire and reported herein. RESULTS: During the study period, 145 patients underwent 164 procedures of S-P 3D EABS. One hundred fifty (91.5%) procedures were endoscopic-assisted nipple-sparing mastectomy (S-P 3D E-NSM; 117 therapeutic procedures for breast cancer, 13 prophylactic mastectomies, 20 procedures for gynecomastia). Fourteen (8.5%) procedures of endoscopic-assisted breast-conserving surgery (S-P 3D E-BCS) were performed (12 S-P 3D E-BCS, 2 S-P 3D E-BCS with 3D videoscope-assisted partial breast reconstruction, which was 1 case of latissimus dorsi flap and 1 case of omental flap). The mean operative time was 245 ± 110 min in S-P 3D E-NSM and 260 ± 142 min in S-P 3D E-BCS. The mean intraoperative blood loss was 49.7 ± 46.9 ml in S-P 3D E-NSM and 32.8 ± 17.5 ml in S-P 3D E-BCS. Subnipple biopsy showed positive malignancy in 3 (2.6%) S-P 3D E-NSM patients. None of the S-P 3D E-BCS patients found margin involvement; however, 3 (2.6%) reported margin involvement in S-P 3D E-NSM patients. Thirty-two complications were found (24.6%): 7 (5.3%) transient nipple-areolar complex (NAC) ischemia, 7 (5.3%) partial NAC necrosis, 1 (0.7%) total NAC necrosis, and 1 (0.7%) implant loss. During the mean follow-up time of 34 months, there were 2 (1.5%) patients with locoregional recurrence, 9 (6.9%) distant metastasis, and 2 (1.5%) mortality. 78.6% (77/98) of patients answering the cosmetic-evaluated questionnaire reported good and excellent overall satisfaction. CONCLUSIONS: S-P 3D EABS is a novel surgical innovation, which is able to perform safely in either malignant or benign breast conditions and offer promising cosmetic results.

Factors associated with alteration of nipple or skin sensation and impact of duration of time following nipple-sparing mastectomy (NSM): an analysis of 460 cases with comparison of conventional versus endoscopic- or robotic-assisted NSM.

BACKGROUND: The current study aims to evaluate the nipple and skin sensation following nipple-sparing mastectomy (NSM) and identify patient-, surgical-, or treatment-related factors affecting nipple or skin sensation in this cohort. METHODS: Patients who received NSM with postoperative nipple and skin sensation test evaluation at a single institution over the past 10 years were retrospectively retrieved from a prospectively collected breast cancer surgery database. RESULTS: A total of 460 NSM procedures were included in this current study, with the mean age of 48.3 ± 9.1. Three-hundred eighty-three (83.3%) patients had breast reconstructions. One-hundred seventy-four (37.8%) received conventional NSM (C-NSM), 195 (42.4%) endoscopic-assisted NSM (E-NSM), and 91 (19.8%) robotic-assisted NSM (R-NSM) procedures. For nipple sensation assessment, 15 (3.3%) were grade 0, 83 (18.2%) grade I, 229 (49.7%) grade II, and 133 (28.9%) grade III (normal sensation), respectively, with mean grade score of 2.1 ± 0.7. The preserved (grade III) nipple sensation rate was 36.2% (63/174) in the C-NSM group, 26.7% (52/195) in the E-NSM group, and 19.7% (18/91) in the R-NSM group (P = 0.06). The "time since surgery to last evaluation" was significantly longer in the C-NSM group (45.6 ± 34 months) or E-NSM group (44.7 ± 35.8 months) as compared to R-NSM group (31.8 ± 16 months, P < 0.01). In multivariate analysis, peri-areolar incision showed higher grade of nipple sensation (OR: 2.1, P = 0.02) compared to upper outer quadrant incision, and longer follow-up time post-NSM showed significant improvement of nipple or skin sensation (> 60 months vs. ≦ 12 months: nipple odds ratio (OR) = 5.75, P < 0.01; skin, OR = 1.97, P < 0.05). CONCLUSION: Our current analysis showed some factors to be related to postoperative nipple or skin sensation, and longer "time after surgery" was associated with significant improvement of nipple and skin sensation in patients who received NSM, regardless of the surgical approaches. SYNOPSIS: Our current analysis showed a significant portion of patients with decrease or loss of nipple or skin sensation after nipple-sparing mastectomy (NSM). Several factors associated with preserved nipple or skin sensation were identified, including age, surgical methods, surgical wound location, and association of time from surgery showing that improvement of partial nipple or skin sensation was evident after a longer follow-up.

Nipple-areolar complex (NAC) or skin flap ischemia necrosis post nipple-sparing mastectomy (NSM)-analysis of clinicopathologic factors and breast magnetic resonance imaging (MRI) features.

BACKGROUND: The purpose of this study is to identify clinicopathologic factors and/or preoperative MRI vascular patterns in the prediction of ischemia necrosis of the nipple-areola complex (NAC) or skin flap post nipple-sparing mastectomy (NSM). METHODS: We performed a retrospective analysis of 441 NSM procedures from January 2011 to September 2021 from the breast cancer database at our institution. The ischemia necrosis of NAC or skin flap was evaluated in correlation with clinicopathologic factors and types of skin incision. Patients who received NSM with preoperative MRI evaluation were further evaluated for the relationship between vascular pattern and the impact on ischemia necrosis of NAC or skin flap. RESULTS: A total of 441 cases with NSM were enrolled in the current study, and the mean age of the cases was 49.1 ± 9.8 years old. A total of 41 (9.3%) NSM procedures were found to have NAC ischemia/necrosis. Risk factors were evaluated of which old age, large mastectomy specimen weight (> 450 g), and peri-areola incision were identified as predictors of NAC necrosis. Two-hundred seventy NSM procedures also received preoperative MRI, and the blood supply pattern was 18% single-vessel type and 82% double-vessel pattern. There were no correlations between MRI blood supply patterns or types of skin flap incisions with ischemia necrosis of NAC. There were also no correlations between blood loss and the pattern or size of the blood vessel. CONCLUSION: Factors such as the type of skin incision, age, and size of mastectomy weight played an important role in determining ischemia necrosis of NAC; however, MRI vascular (single or dual vessel supply) pattern was not a significant predictive factor.

The impact of body mass index (BMI) on MRI diagnostic performance and surgical management for axillary lymph node in breast cancer.

BACKGROUND: We hypothesized that different BMI might have different impact on pre-operative MRI axillary lymph node (ALN) prediction accuracy and thereby subsequent surgical lymph node management. The aim of this study is to evaluate the effect of BMI on presentation, surgical treatment, and MRI performance characteristics of breast cancer with the main focus on ALN metastasis evaluation. METHODS: The medical records of patients with primary invasive breast cancer who had pre-operative breast MRI and underwent surgical resection were retrospectively reviewed. They were categorized into 3 groups in this study: underweight (BMI < 18.5), normal (BMI of 18.5 to 24), and overweight (BMI > 24). Patients' characteristics, surgical management, and MRI performance for axillary evaluation between the 3 groups were compared. RESULTS: A total of 2084 invasive breast cancer patients with a mean age of 53.4 ± 11.2 years were included. Overweight women had a higher rate of breast conserving surgery (56.7% vs. 54.5% and 52.1%) and initial axillary lymph node dissection (15.9% vs. 12.2% and 8.5%) if compared to normal and underweight women. Although the post-operative ALN positive rates were similar between the 3 groups, overweight women were significantly found to have more axillary metastasis on MRI compared with normal and underweight women (50.2% vs 37.7% and 18.3%). There was lower accuracy in terms of MRI prediction in overweight women (65.1%) than in normal and underweight women (67.8% and 76.1%). CONCLUSION: Our findings suggest that BMI may influence the diagnostic performance on MRI on ALN involvement and the surgical management of the axilla in overweight to obese women with breast cancer.

Neoadjuvant afatinib with paclitaxel for triple-negative breast cancer and the molecular characteristics in responders and non-responders.

BACKGROUND: The prognosis of triple-negative breast cancer (TNBC) is worse and a major proportion of TNBC expresses epidermal growth factor receptor (EGFR). Afatinib can inhibit EGFR signal pathway; however, its treatment effect for TNBC is unknown. Thus, we aimed to assess the efficacy and biomarkers of afatinib in combination with paclitaxel in a neoadjuvant setting. METHODS: Patients with stage II to III TNBC were enrolled. They received 40 mg of afatinib daily for 14 days, followed by daily afatinib and weekly paclitaxel (80 mg/m2) every 21 days for four to six cycles. To explore the mechanisms of responsiveness and non-responsiveness, 409 cancer-associated genes were sequenced. RESULTS: Twenty-one patients were enrolled and one patient achieved a complete clinical response; however, a 2 mm residual tumor was noted in the surgical specimen. Overall, 33.0% patients were responders. Fifteen patients received molecular testing. No activated mutation of EGFR or Her2 were found. Activated PI3K or JAK2 pathway were trended to associate with non-responder (p = 0.057). Mutation of homologous recombination (HR) genes were correlated with non-responsiveness (p = 0.005). Seven patients did not have altered PI3K, JAK2 or HR pathway; six (85.7%) of them were responder. Patients with the amplified DAXX gene was associated with a favorable trend of response (p = 0.109). CONCLUSION: Adding afatinib to neoadjuvant paclitaxel generated a modest effect in TNBC. Exploratory molecular analysis suggested that activated PI3K, JAK2 pathways and mutation of HR genes were associated with therapeutic non-responsiveness, and amplification of DAXX genes was associated with responsiveness to afatinib in combination with paclitaxel.

Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens.

PURPOSE: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. METHODS: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. RESULTS: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. CONCLUSION: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. CLINICAL TRIAL REGISTRATION: NCT01808573.

Oncologic Outcome of Endoscopic Assisted Breast Surgery Compared with Conventional Approach in Breast Cancer: An Analysis of 3426 Primary Operable Breast Cancer Patients from Single Institute with and Without Propensity Score Matching.

BACKGROUND: Endoscopy-assisted breast surgery (EABS) performed through minimal axillary and/or peri-areolar incisions is a possible alternative to conventional breast surgery (CBS) for certain patients with breast cancer. In this study, we report the oncologic safety results of EABS compared with CBS. METHODS: Patients underwent EABS for breast cancer during the period June 2010 to March 2020 were collected from the EABS database from single institute, and another cohort of patients, who received CBS, were identified to determine the effectiveness and oncologic safety of EABS. A case-control study was conducted using propensity score matching (PSM) to prevent bias from cases selection. RESULTS: A total of 3426 patients were enrolled in the current study, including 405 patients receiving EABS and 3021 underwent CBS. Before PSM, patients selected for EABS tend to be smaller in tumor size, node negative, early stage, low histologic grade, and HER-2 negative. After PSM, 343 patients underwent EABS were compared with another 343 patients received CBS. The margin involved rate in EABS group is 2.6%, and 5.6% in CBS group (p = 0.054) after PSM. In breast conserving cases, the margin involved rates were 2% in EABS group, and 7.2% in CBS group (p = 0.04). In Kaplan-Meier survival curves analysis, there was no difference in local regional recurrence (p = 0.89), distant metastasis (p = 0.08), and overall survival (p = 0.14). CONCLUSION: The preliminary oncologic safety analysis from current study showed EABS is a safe procedure and results in low margin involved rate, and no increase of locoregional recurrence, distant metastasis or mortality compared with CBS.

Single-Port Three-Dimensional (3D) Videoscope-Assisted Endoscopic Nipple-Sparing Mastectomy in the Management of Breast Cancer: Technique, Clinical Outcomes, Medical Cost, Learning Curve, and Patient-Reported Aesthetic Results from 80 Preliminary Procedures.

BACKGROUND: The preliminary results of an innovative surgical technique, which incorporated single-port three-dimensional (3D) videoscope and instruments for endoscopic nipple-sparing mastectomy (E-NSM), were reported. METHODS: The medical records of patients who underwent single-port 3D E-NSM for breast cancer from August 2018 to September 2020 were analyzed, and the preliminary outcome of this procedure as well as the patient-reported aesthetic results are described in this article. RESULTS: The study enrolled 70 patients who received 80 procedures of single-port 3D E-NSM. The mean operation time was 158 ± 36 min, and the mean blood loss was 41 ± 26 ml. Three procedures (3.8 %) associated with delayed axillary wound-healing, eight cases of transient nipple ischemia (10 %), three cases of partial nipple ischemia/necrosis (3.7 %), and one case of total nipple-areolar complex (NAC) necrosis (1.3 %) were observed. No patient had margin involvement. Satisfaction rates of approximately 90 % were observed in terms of postoperative scar appearance, location, and length. Most of the patients (87.8 %) reported that they would choose the same operation again if given the chance to do so. The overall cost of a single-port 3D E-NSM was 7522 ± 470 U.S. dollars. According to cumulative sum (CUSUM) plot analysis, about 14 cases were needed for surgeons to familiarize themselves with single-port 3D E-NSM and immediate gel implant reconstruction and to decrease their operation time significantly in the initial learning phase. CONCLUSION: Single-port 3D E-NSM, a safe, efficient, lower-cost procedure, is associated with a good aesthetic result. It is a promising new technique for breast cancer patients indicated for mastectomy, but long-term oncologic safety follow-up evaluation still is needed.

Revisit the practice of lymph node biopsy in patients diagnosed as ductal carcinoma in situ before operation: a retrospective analysis of 682 cases and evaluation of the role of breast MRI.

BACKGROUND: The optimal axillary lymph node (ALN) management strategy in patients diagnosed with ductal carcinoma in situ (DCIS) preoperatively remains controversial. The value of breast magnetic resonance imaging (MRI) to predict ALN metastasis pre-operative DCIS patients was evaluated. METHODS: Patients with primary DCIS with or without pre-operative breast MRI evaluation and underwent breast surgery were recruited from single institution. The value of breast MRI for ALN evaluation, predictors of breast and ALN surgeries, upgrade from DCIS to invasive cancer, and ALN metastasis were analyzed. RESULTS: A total of 682 cases with pre-operative diagnosis of DCIS were enrolled in current study. The rate of upgrade to invasive cancer were found in 34.2% of specimen, and this upgrade rate is 23% for patients who received breast conserving surgery and 40.7% for mastectomy (p < 0.01). Large pre-operative imaging tumor size and post-operative invasive component were risk factors to ALN metastasis. Breast MRI had 53.8% sensitivity, 77.8% specificity, 14.9% positive predictive value, 95.9% negative predictive value (NPV), and 76.2% accuracy to predict ALN metastasis in pre-OP DCIS patients. In MRI node-negative breast cancer patients with MRI tumor size < 3 cm, the NPV was 96.4%, and all these false-negative cases were N1. Pre-OP diagnosed DCIS patients with MRI tumor size < 3 cm and node negative suitable for BCS could safely omit SLNB if whole breast radiotherapy is to be performed. CONCLUSION: Breast MRI had high NPV to predict ALN metastasis in pre-OP DCIS patients, which is useful and could be provided as shared decision-making reference.

Robotic- Versus Endoscopic-Assisted Nipple-Sparing Mastectomy with Immediate Prosthesis Breast Reconstruction in the Management of Breast Cancer: A Case-Control Comparison Study with Analysis of Clinical Outcomes, Learning Curve, Patient-Reported Aesthetic Results, and Medical Cost.

BACKGROUND: New surgical innovations of nipple-sparing mastectomy (NSM), such as endoscopic NSM (E-NSM) or robotic NSM (R-NSM), were emerging. However, there was a lack of evidence comparing the effectiveness and safety in the management of breast cancer. METHODS: A case-control comparison study was conducted for patients with breast cancer underwent E-NSM or R-NSM with immediate prosthesis breast reconstruction (IPBR) from July 2010 to February 2019 at a single institution to compare the clinical outcomes, learning curve, patient-reported cosmetic results, and medical cost. RESULTS: A total of 91 E-NSM and 40 R-NSM procedures were retrieved and analyzed. The surgical margin involvement rate in both R-NSM (2.5%) and E-NSM (4.4%) procedures were relatively low (P = 0.52). The R-NSM group was associated with higher satisfaction rates in terms of scar appearance, scar length, and surgical wound position compared with the E-NSM group. Compared with E-NSM, the R-NSM operation time took longer (241 ± 61 vs. 215 ± 70 min, P = 0.01), less blood loss (32 ± 29 vs. 79 ± 62 ml, P < 0.01), and higher medical cost (10,587 ± 554 vs. 6855 ± 936 U.S. dollars, P < 0.01). There was no statistically significant difference in nipple ischemia/necrosis or overall complication between R-NSM and E-NSM. In the learning curve analysis, it took the 27th procedure in E-NSM and 10th procedure in R-NSM to decrease operation time significantly. CONCLUSIONS: R-NSM was associated with higher wound-related satisfaction, lesser blood loss, and shorter learning curve compared with E-NSM, however, at the price of longer operation time and higher medical cost.

Robotic Nipple-Sparing Mastectomy and Immediate Breast Reconstruction with Gel Implant: Technique, Preliminary Results and Patient-Reported Cosmetic Outcome.

BACKGROUND: Experience with application of a robotic surgery platform in the management of breast cancer is limited. The preliminary results of the robotic nipple-sparing mastectomy (R-NSM) and immediate breast reconstruction (IBR) with Gel implant procedure are reported. METHODS: The medical records of patients from a single institution who underwent an R-NSM and IBR with Gel implant procedure for breast cancer during the period March 2017 to February 2018 were assessed. Data on clinicopathologic characteristics, type of surgery, complications, and recurrence were analyzed to determine the effectiveness and oncologic safety of R-NSM. Patient-reported cosmetic outcome results were obtained. RESULTS: A total of 22 patients who received 23 R-NSM and IBR with Gel implant procedures were analyzed. The mean operation time for R-NSM was 118.8 ± 50.6 min, and 74.5 ± 26.6 min for Gel implant reconstruction. Docking time quickly dropped from 20 to 6-8 min, and the time needed to complete R-NSM was usually completed within 100 min after accumulation of case experience. Mean blood loss was 37 ± 38.2 mL, and the positive surgical margin rate was 0%. Three (13%) patients had transit nipple ischemia change, and no total nipple-areolar complex necrosis cases were observed. No local recurrence or mortality was found during a mean 6.9 ± 3.5 months of follow-up. All 22 patients were satisfied with the postoperative aesthetic outcome. CONCLUSION: From our preliminary experience, R-NSM and IBR with Gel implant is a safe procedure, with good cosmetic results, and could be a promising new technique for breast cancer patients indicated for mastectomy.

Single-Axillary-Incision Endoscopic-Assisted Hybrid Technique for Nipple-Sparing Mastectomy: Technique, Preliminary Results, and Patient-Reported Cosmetic Outcome from Preliminary 50 Procedures.

BACKGROUND: A new hybrid technique for single-axillary-incision endoscopic-assisted nipple-sparing mastectomy (E-NSM) was introduced. Preliminary results are reported. METHODS: Patients who received single-axillary-incision E-NSM from August 2013 to August 2017 were searched from a single institution. Data were analyzed to determine the effectiveness and oncologic safety of single-axillary-incision E-NSM. Patient-oriented cosmetic outcome report was also obtained. RESULTS: During the study period, a total of 50 E-NSM with single-incision procedures were performed in 41 female patients with breast cancer, including 11 (26.8%) patients with bilateral disease. Their mean age was 45.3 ± 8.4 years. The mean size of tumors encountered during the 50 single-incision E-NSM procedures was 2.3 ± 1.8 (0.1-7.3) cm for invasive tumors and 2.6 ± 1.7 (0.2-5.7) cm for carcinoma in situ lesions. Six (12%) of those tumors were multifocal/multicentric. Lymph node metastasis was found during 12% of the procedures. Forty-five (90%) received immediate breast reconstruction with gel implant. Mean operating time was 244.3 ± 82.8 min. The overall complication rate was 6%, and no total nipple necrosis or implant loss was observed. No locoregional recurrence or distant metastasis was found during mean follow-up of 21.6 months. About 94.4% of patients were satisfied with the postoperative scar location and wound length. All patients who responded would choose the same operation again. CONCLUSIONS: The proposed single-axillary-incision endoscopic hybrid technique for nipple-sparing mastectomy was a safe procedure with low morbidity and associated with high patient satisfaction.

Regret about surgical decisions among early-stage breast cancer patients: Effects of the congruence between patients' preferred and actual decision-making roles.

OBJECTIVE: Early-stage breast cancer patients generally receive either a mastectomy or a lumpectomy, either by their own choice or that of their surgeon. Sometimes, there is regret about the decision afterward. To better understand regret about surgical decisions, this study examined 2 possibilities: The first is that women who take a dominant or collaborative role in decision making about the surgery express less regret afterward. The second is that congruence between preferred role and actual role predicts less regret. We also explored whether disease stage moderates the relationship between role congruence and decisional regret. METHODS: In a cross-sectional design, 154 women diagnosed with breast cancer completed a survey assessing decisional role preference and actual decisional role, a measure of post-decision regret, and a measure of disturbances related to breast cancer treatment. Hierarchical regression was used to investigate prediction of decisional regret. RESULTS: Role congruence, not actual decisional role, was significantly associated with less decisional regret, independent of all the control variables. The interaction between disease stage and role congruence was also significant, showing that mismatch relates to regret only in women with more advanced disease. CONCLUSIONS: Our findings suggest that cancer patients could benefit from tailored decision support concerning their decisional role preferences in the complex scenario of medical and personal factors during the surgical decision.

The Application of Non-Invasive Apoptosis Detection Sensor (NIADS) on Histone Deacetylation Inhibitor (HDACi)-Induced Breast Cancer Cell Death.

Breast cancer is the most common malignancy in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) subtype is a breast cancer subset without ER (estrogen receptor), PR (progesterone receptor) and HER2 (human epidermal growth factor receptor 2) expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether histone deacetylation inhibitor (HDACi) could be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enriched breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence-based live cell non-invasive apoptosis detection sensor (NIADS) detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also contribute a synergic anti-cancer effect with co-treatment of chemotherapeutic agent such as doxorubicin on TNBC cells (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in the clinic.

Evaluating genetic variants associated with breast cancer risk in high and moderate-penetrance genes in Asians.

Over the past 20 years, high-penetrance pathogenic mutations in genes BRCA1, BRCA2, TP53, PTEN, STK11 and CDH1 and moderate-penetrance mutations in genes CHEK2, ATM, BRIP1, PALB2, RAD51C, RAD50 and NBN have been identified for breast cancer. In this study, we investigated whether there are additional variants in these 13 genes associated with breast cancer among women of Asian ancestry. We analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and 6624 controls of Asian descent included in the Breast Cancer Association Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included in the Shanghai Breast Cancer Genetics Study (SBCGS). We found three missense variants with minor allele frequency (MAF) <0.05: rs80358978 (Gly2508Ser), rs80359065 (Lys2729Asn) and rs11571653 (Met784Val) in the BRCA2 gene, showing statistically significant associations with breast cancer risk, with P-values of 1.2 × 10-4, 1.0 × 10-3 and 5.0 × 10-3, respectively. In addition, we found four low-frequency variants (rs8176085, rs799923, rs8176173 and rs8176258) in the BRCA1 gene, one common variant in the CHEK2 gene (rs9620817), and one common variant in the PALB2 gene (rs13330119) associated with breast cancer risk at P < 0.01. Our study identified several new risk variants in BRCA1, BRCA2, CHEK2, and PALB2 genes in relation to breast cancer risk in Asian women. These results provide further insights that, in addition to the high/moderate penetrance mutations, other low-penetrance variants in these genes may also contribute to breast cancer risk.

Endoscopy-assisted surgery for the management of benign breast tumors: technique, learning curve, and patient-reported outcome from preliminary 323 procedures.

BACKGROUND: Endoscopy-assisted breast surgery (EABS), a technique that optimizes cosmetic outcome because it is performed through small wounds hidden in inconspicuous areas, could be an alternative surgical technique for benign breast tumors. In this study, we report the preliminary results of 323 EABS procedures performed at our institution for the management of benign breast tumors. METHODS: The medical records of patients who underwent EABS for benign breast lesions during the periods August 2010 to December 2015 were collected from the Changhua Christian Hospital EABS database. Data on clinicopathologic characteristics, type of surgery, hospital stay, and complications were analyzed to determine the effectiveness of the procedure for benign breast tumors. The operating time with the number of procedure performed was analyzed for learning curve evaluation. Patient satisfaction with cosmetic outcome was evaluated with a self-report questionnaire. RESULTS: A total of 323 EABS procedures were performed in 286 patients with benign breast lesions, including 249 (90.5%) patients with unilateral lesions. The mean age was 36 years, the mean tumor size was 2.2 cm, and the mean distance from the nipple to the tumor was 5.2 cm. Most (93.8%, 303/323) of these tumors were excised through a transareolar wound, 2.4% (8/323) through an axillary wound, and 0.3% (1/323) through the infra-mammary fold. Histopathologic analysis revealed that 63.5% (202/318) of the tumors were fibroadenoma-related lesions. The mean operative time was 81.4 min (59~89 min), which was decreased with experience increased. The overall rate of complications was 6.5%, and all were minor and wound-related. Among the 110 patients who participated in the self-report cosmetic outcome evaluation, 85.4% reported being satisfied with the cosmetic result, and almost all were satisfied with breast symmetry. Of the patients interviewed, 92.7% reported that they would choose the same procedure if they had to undergo the operation again. CONCLUSIONS: Our preliminary results show that transareolar video-assisted breast surgery is a safe and effective procedure with good cosmetic outcome and that it could be appropriate for patients with moderate to large peripherally located breast tumors. TRIAL REGISTRATION: CCH-IRB No.15115. Registered 14 December 2015 (retrospectively registered).

Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.

BACKGROUND: Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. METHODS: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. RESULTS: We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P < 0.05. Compared with women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15-3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively. CONCLUSION: Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.