Is minimal-accessed (endoscopic- or robotic-assisted) nipple-sparing mastectomy contraindicated for large breasts?

BACKGROUND: In the developmental stage of minimal-accessed nipple-sparing mastectomy (MA-NSM), selecting patients with small to medium-sized breasts was common for better cosmetic outcomes and oncological safety. However, the suitability of MA-NSM for large, ptotic breasts remained uncertain. This retrospective study aim to assess MA-NSM outcomes in patients with large breasts. MATERIALS AND METHODS: This retrospective study included patients receiving conventional NSM (C-NSM) and MA-NSM from January 2011 to September 2022, at a single institution. We analyzed perioperative parameters and clinical outcomes based on breast specimen size, classified as small (≤300 g), medium (>300-450 g), large (>450-600 g), and very large (>600 g). RESULTS: A total of 728 patients was enrolled. C-NSM was performed in 51% (371/728) of cases, while MA-NSM was done in 49% (357/728). The overall complication rate of MA-NSM was comparable to C-NSM (p = 0.573), but severe complications (Clavien-Dindo, CD III) was significantly reported more following C-NSM, regardless of breast size. During a median follow-up of 52 months, no significant difference in oncological outcomes was observed. Comparing MA-NSM and C-NSM outcomes in large-very large breasts (>450 g), MA-NSM demonstrated significantly less blood loss (p = 0.036) and lower incidence of severe complications (CD ≥ III) compared to C-NSM (p = 0.002). CONCLUSION: MA-NSM is feasible for large breasts and offers benefits by reducing blood loss and decreasing the incidence of severe complications (CD ≥ III) in this patient group.

Scarless totally implantable venous access port (TIVAP) implantation: Surgical technique, preliminary results, learning curve, and patients-reported outcome in 125 breast cancer patients.

BACKGROUND: Minimal-access (endoscopic or robotic-assisted) breast surgery has been increasingly performed and shown better cosmetic results. However, location of totally implantable venous access port (TIVAP) for systemic treatment at anterior chest may compromise its aesthetic benefits. Therefore, we proposed a new scarless technique for TIVAP implantation, and reported the preliminary results, learning curve, and patients-surveyed outcome. METHODS: Surgical technique of the new "scarless" TIVAP implantation was proposed. Patients receiving this procedure in a single institution were included. The preliminary results of the scarless TIVAP implantation, learning curve, and patient-reported outcome were analyzed and reported. RESULTS: A total of 125 breast cancer patients received scarless TIVAP procedures were enrolled. The primary success rate of the scarless TIVAP implantation was 100%. Mean operative time was 46 ± 14 min. Mean amount of blood loss was 8.5 ± 3.2 ml. The cumulative sum plot showed operation time significantly decreased after 24th cases. In the initial learning phase, the mean operative time was 55 ± 17 min, and decreased to 43 ± 12 min in the later mature phase (P = 0.003). There were 5 (4%) complications detected, which included 1 (0.8%) seroma formation, 2 (1.6%) revisions, and 2 (1.6%) unplanned explantations. From patients-evaluated questionnaires, more than 90% of responders were satisfied with aesthetic results, experience during surgery, and application of scarless TIVAP for systemic therapy. CONCLUSIONS: The scarless TIVAP implantation is a safe & reliable procedure with high patients-reported aesthetic satisfaction, and could be an alternative TIVAP procedure for patients requiring chemotherapy and desiring a less noticeable scar.

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.

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.

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.

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.

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.

Use of Magnetic Resonance Imaging for Evaluating Residual Breast Tissue After Robotic-Assisted Nipple-Sparing Mastectomy in Women With Early Breast Cancer.

OBJECTIVE: Prospective studies on postoperative residual breast tissue (RBT) after robotic-assisted nipple-sparing mastectomy (R-NSM) for breast cancer are limited. RBT presents an unknown risk of local recurrence or the development of new cancer after curative or risk-reducing mastectomies. This study investigated the technical feasibility of using magnetic resonance imaging (MRI) to evaluate RBT after R-NSM in women with breast cancer. MATERIALS AND METHODS: In this prospective pilot study, 105 patients, who underwent R-NSM for breast cancer at Changhua Christian Hospital between March 2017 and May 2022, were subjected to postoperative breast MRI to evaluate the presence and location of RBT. The postoperative MRI scans of 43 patients (age, 47.8 ± 8.5 years), with existing preoperative MRI scans, were evaluated for the presence and location of RBT. In total, 54 R-NSM procedures were performed. In parallel, we reviewed the literature on RBT after nipple-sparing mastectomy, considering its prevalence. RESULTS: RBT was detected in 7 (13.0%) of the 54 mastectomies (6 of the 48 therapeutic mastectomies and 1 of the 6 prophylactic mastectomies). The most common location for RBT was behind the nipple-areolar complex (5 of 7 [71.4%]). Another RBT was found in the upper inner quadrant (2 of 7 [28.6%]). Among the six patients who underwent RBT after therapeutic mastectomies, one patient developed a local recurrence of the skin flap. The other five patients with RBT after therapeutic mastectomies remained disease-free. CONCLUSION: R-NSM, a surgical innovation, does not seem to increase the prevalence of RBT, and breast MRI showed feasibility as a noninvasive imaging tool for evaluating the presence and location of RBT.

Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value-an analysis of 2473 invasive breast cancer patients.

BACKGROUND: The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance. MATERIAL AND METHODS: Patients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis. RESULTS: 2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI-ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden. CONCLUSION: The diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Unveiling the Power of Anticancer Drug Screening: A Clinical Case Study Comparing the Effectiveness of Hollow Fiber Assay Microtube Array Membrane (MTAM-HFA) in Breast Cancer Patients.

Breast cancer is a severe public health problem, and early treatment with powerful anticancer drugs is critical for success. The researchers investigated the clinical results of a novel screening tool termed Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA) in breast cancer patients in this clinical investigation. In all trial participants, the MTAM-HFA was utilized to identify active medicines for the treatment of breast cancer. The MTAM-HFA was shown to be extremely useful in predicting patient response to anticancer medication therapy in this study. Furthermore, the substantial association between the MTAM-HFA screening outcome and the clinical outcome of the respective patients emphasizes the promise of this unique screening technology in discovering effective anticancer medication combinations for the treatment of breast cancer. These findings indicate that the MTAM-HFA has clinical significance and might be a valuable tool in the development of tailored therapy for cancer care. This study provides helpful information for physicians and scientists working on breast cancer therapy research. The potential benefits of employing MTAM-HFA to find accurate therapies for breast cancer patients might lead to enhanced personalized medicine approaches to cancer care, resulting in better patient outcomes. Overall, the MTAM-HFA screening approach has the potential to revolutionize customized cancer therapy, providing hope to both patients and physicians.

Oncoplastic and reconstructive breast surgeon performance and impact on breast reconstructions: Clinical outcomes, learning curve, and patients' satisfaction.

BACKGROUND: Compared to mastectomy alone, the addition of breast reconstruction could improve quality of life and it is usually performed by two-team approach, which consisted of both breast surgeons and plastic surgeons. This study aims to illustrate the positive impacts of the dual-trained oncoplastic reconstructive breast surgeon (ORBS) and reveal the factors influencing reconstruction rates. METHODS: This retrospective study enrolled 542 breast cancer patients who undergone mastectomy with reconstruction performed by a particular ORBS between January 2011 and December 2021 at a single institution. Clinical and oncological outcomes, impact of case accumulation on performance and patient-reported aesthetic satisfactions were analyzed and reported. Furthermore, in this study 1851 breast cancer patients treated with mastectomy combined with or without breast reconstructions, which included 542 performed by ORBS, were reviewed to identify factors affecting breast reconstructions. RESULTS: Among the 524 breast reconstructions performed by the ORBS, 73.6% were gel implant reconstructions, 2.7% were tissue expanders, 19.5% were transverse rectus abdominal myocutaneous (TRAM) flaps, 2.7% were latissimus dorsi (LD) flaps, 0.8% were omentum flaps, and 0.8% involved LD flaps and implants. There was no total flap loss in the 124 autologous reconstructions, and the implant loss rate was 1.2% (5/403). Patient-reported aesthetic evaluations showed that 95% of the patients were satisfied. As the ORBS's accumulated case experiences, the implant loss rate decreased, and the overall satisfaction rate increased. According to the cumulative sum plot learning curve analysis, it took 58 procedures for the ORBS to shorten the operative time. In multivariate analysis, younger age, MRI, nipple sparing mastectomy, ORBS, and high-volume surgeon were factors related to breast reconstruction. CONCLUSION: The current study demonstrated that a breast surgeon after adequate training could become an ORBS and perform mastectomies with various types of breast reconstruction with acceptable clinical and oncological outcomes for breast cancer patients. ORBSs could increase breast reconstruction rates, which remain low worldwide.

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.

Regulation of mitochondrial fusion and mitophagy by intra-tumoral delivery of membrane-fused mitochondria or Midiv-1 enhances sensitivity to doxorubicin in triple-negative breast cancer.

Increasing mitochondrial fusion by intra-tumoral grafting of membrane-fused mitochondria created with Pep-1 conjugation (P-Mito) contributes to breast cancer treatment, but it needs to be validated. Using mitochondrial division inhibitor-1 (Mdivi-1, Mdi) to disturb mitochondrial dynamics, we showed that the antitumor action of P-Mito in a mouse model of triple-negative breast cancer depends upon mitochondrial fusion and that Mdi treatment alone is ineffective. P-Mito significantly enhanced Doxorubicin (Dox) sensitivity by inducing mitochondrial fusion and mitophagy, and the same efficiency was also achieved with Mdi by inhibiting mitophagy. Cell death was induced via the p53 pathway and AIF nuclear translocation in the case of P-Mito, versus the caspase-dependent pathway for Mdi. Notably, both mitochondrial treatments reduced oxidative stress and blood vessel density of xenograft tumors, especially P-Mito, which was accompanied by inhibition of nuclear factor kappa-B activation. Furthermore, through enrichment analysis, four microRNAs in serum microvesicles induced by P-Mito caused expression of predicted targets via the PI3K-Akt pathway, and significantly impacted regulation of nuclear processes and myeloid cell differentiation. Clustering of gene-sets implicated a major steroid catabolic network. This study showed diverse roles of mitochondria in breast cancer and revealed effective adjuvant therapy targeting mitochondrial fusion and mitophagy.

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.

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.

Minimal Access (Endoscopic and Robotic) Breast Surgery in the Surgical Treatment of Early Breast Cancer-Trend and Clinical Outcome From a Single-Surgeon Experience Over 10 Years.

OBJECTIVE: Endoscopic assisted breast surgery (EABS) or robotic assisted breast surgery (RABS) performed through minimal axillary and/or peri-areolar incisions has become the representative of minimal access breast surgery (MABS). We report the trend and clinical outcome of MABS for treatment of breast cancer. METHODS: Information on patients who underwent breast cancer operation by the principal investigator during the period of 2011 to 2020 was collected from a single institute for analysis. The clinical outcome, trend, and cost of MABS were analyzed and compared with conventional breast surgery (CBS). RESULTS: A total of 824 breast cancer patients operated by a single surgeon were enrolled in this study: 254 received CBS and 570 received MABS, namely, 476 EABS and 94 RABS. From 2011 to 2020, the number of MABS performed annually has shown an increasing trend. Compared with CBS, MABS such as breast conserving surgery and nipple sparing mastectomy (NSM) have effectively reduced wound scar length. Since the sequential uprise from conventional NSM (C-NSM), dual-axillary-areolar-incision two dimensional (2D) endoscopic assisted NSM (E-NSM), single-axillary-incision E-NSM, robotic assisted NSM (R-NSM), and single-port 3D E-NSM, the development of minimal access mastectomies increasingly paralleled with NSM. The operation time of various MABS decreased significantly and showed no statistical difference compared with CBS. R-NSM was associated with highest cost, followed by 3D E-NSM, E-NSM, and C-NSM. The positive surgical margin rate and local recurrence rate of MABS and CBS were not statistically different. CONCLUSION: MABS showed comparable clinical outcome and preliminary oncologic safety as CBS and has been increasingly performed as the surgical treatment of breast cancer, especially minimal access NSM.

Impact of pre-operative breast magnetic resonance imaging on contralateral synchronous and metachronous breast cancer detection-A case control comparison study with 1468 primary operable breast cancer patients with mean follow-up of 102 months.

BACKGROUND: Women with unilateral breast cancer are at an increased risk for the development of contralateral breast cancers. We hypothesis that combined breast MRI would detect more contralateral synchronous breast cancer than conventional imaging alone, and resulted in less contralateral metachronous breast cancer during follow-up. METHODS: We retrospectively collected two groups of breast cancer patients diagnosed from 2009 to 2013 for evaluating the effectiveness and value of adding pre-operative breast MRI to conventional breast images (mammography and sonography) for detection of contralateral synchronous breast cancer. The new metachronous contralateral breast cancer diagnosed during follow-up was prospectively evaluated and compared. RESULTS: Group A (n = 733) comprised patients who underwent conventional preoperative imaging and group B (n = 735) combined with MRI were enrolled and compared. Seventy (9.5%) of the group B patients were found to have contralateral lesions detected by breast MRI, and 65.7% of these lesions only visible with MRI. The positive predictive value of breast MRI detected contralateral lesions was 48.8%. With the addition of breast MRI to conventional imaging studies, more surgical excisions were performed in contralateral breasts (6% (44/735) versus 1.4% (10/733), P< 0.01), more synchronous contralateral breast cancer detected (2.9% (21/735) versus 1.1% (8/733), P = 0.02), and resulted in numerical less (2.2% (16/714) versus 3% (22/725), p = 0.3) metachronous contralateral breast cancer during a mean follow-up of 102 months. CONCLUSIONS: Our study provides useful estimates of the pre-operative breast MRI for the increased detection of contralateral synchronous breast cancer and less subsequent contralateral metachronous breast cancer.

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.

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.

Surgical management of complicated gynecomastia (associated with foreign body injection) with single-port 3-dimensional videoscope-assisted endoscopic subcutaneous mastectomy and concurrent liposuction: A case report.

RATIONALE: Gynecomastia is a common benign breast disorder in men. Surgical management of gynecomastia includes that of a subcutaneous mastectomy with or without concurrent liposuction. Herein, the authors presented a case of complicated gynecomastia (gynecomastia with concurrent foreign body injection) which was successfully managed with an innovative technique that offered acceptable operative time, minimal complications, good recovery and satisfactory aesthetic outcome. PATIENT CONCERNS: A 39-year-old Taiwanese man who developed gynecomastia along with self-injection of foreign body (salad oil) over the past 10 years for breast enlargement presented as symptomatic bilateral breast lumps. DIAGNOSIS: Bedside sonography revealed multiple large droplets of oil in the subcutaneous tissue bilaterally, resembling cystic lesions. INTERVENTION: Bilateral single-port 3-dimensional videoscope-assisted endoscopic subcutaneous mastectomy was performed after bilateral breast liposuction. Operative findings include bilateral gynecomastia and previous bilateral breast foreign body material. The total weight of lipoaspirate was 400 grams and 300 grams for right and left side respectively. Subcutaneous mastectomy specimen weight was 820 grams and 661 grams for right and left breast tissue. OUTCOMES: Operative duration was 315 minutes and intraoperative blood loss at 150 ml. Patient was discharged 2 days after the operation, and subsequent follow up ultrasound showed complete removal of foreign bodies and fibrotic breast tissue. Patient was satisfied with the post-operative aesthetic outcomes. LESSONS: Single-port 3-dimensional videoscope-assisted endoscopic subcutaneous mastectomy with concurrent liposuction is a promising and safe surgical option for patient with complicated gynecomastia and severe fibrosis.