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.

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.

Single institute experience of intraoperative radiation therapy in early-stage breast cancer.

ABSTRACT: Intraoperative radiation therapy (IORT) is an alternative to whole breast irradiation in selected early-stage breast cancer patients. In this single institute analysis, we report the preliminary results of IORT given by Axxent Electronic Brachytherapy (eBT) system.Patients treated with lumpectomy and eBT within a minimum follow-up period of 12 months were analyzed. Eligible criteria include being over the age of 45, having unifocal invasive ductal carcinoma (IDC) or ductal carcinoma in situ <3 cm in diameter, not exhibiting lymph node involvement on preoperative images, and negative sentinel lymph node biopsy. The eBT was given by preloaded radiation plans to deliver a single fraction of 20 Gray (Gy) right after lumpectomy.From January 2016 to April 2019, a total of 103 patients were collected. There were 78 patients with IDC and 25 with ductal carcinoma in situ. At a mean follow-up time of 31.1 months (range, 14.5-54.0 months), the local control rate was 98.1%. Two IDC patients had tumor recurrences (1 local and 1 regional failure). Post-IORT radiotherapy was given to 4 patients. There were no cancer related deaths, no distant metastases, and treatment side effects greater than grade 3 documented.We report the largest single institute analysis using the eBT system in Taiwan. The low recurrence and complication rates at a 31.1 month follow-up time support the use of the eBT system in selected early-stage breast cancer patients.

Evaluation of the Learning Curve in Robotic Nipple-sparing Mastectomy for Breast Cancer.

BACKGROUND: This study discusses the preliminary results of robotic nipple sparing mastectomy (R-NSM) in patients with breast cancer and analyzes the learning curve of the same surgeon in a single medical center. PATIENTS AND METHOD: Patients with breast cancer from a single center who received R-NSM between 2018 to 2020 were recruited for clinical and pathologic tumor characteristics including family history, grade, type of tumor, treatment, and outcome. The learning curve for R-NSM was analyzed by using cumulative sum (CUSUM). RESULTS: A total of 85 R-NSM procedures from 78 patients were evaluated. In the CUSUM plot analysis of the learning curve, a significant decrease in time for mastectomy, reconstruction, and total operation appeared in the 22nd, 23rd, and 26th procedures, respectively. Patients' body weight, gel implant size, and specimen weight had significant correlations with the time for mastectomy. Four (5.6%) patients had nipple partial ischemia, and 1 (1.4%) had total nipple necrosis. The mean follow-up was 11.4 ± 6.2 months; only 1 patient showed recurrence. CONCLUSION: Robotic breast surgery is a feasible method with good cosmetic outcome under suitable patient selection. Oncologic safety is not a reason to stop its development.

Consensus Statement on Robotic Mastectomy-Expert Panel From International Endoscopic and Robotic Breast Surgery Symposium (IERBS) 2019.

OBJECTIVES: To achieve a consensus statement on robotic mastectomy. BACKGROUND: Robotic-assisted surgery has gained much attention especially the results of few case series reporting on the technical feasibility, safety and early oncologic outcomes of robotic-assisted mastectomy in a few centers worldwide. The aim of this consensus statement was to develop and provide standardized guidelines on robotic mastectomy based on consensus statement by a panel of experts from indications to outcome measures and indicators, thereby providing a valuable guide for breast surgeons worldwide. METHODOLOGY: An internationally representative expert panel of 10 surgeons was invited to participate in the generation of a consensus statement. 52 statements were created in 6 domains: indications, contraindications, technical considerations, patient counseling, outcome measures and indicators, training and learning curve assessment. Experts were asked to vote if they agree, disagree or of the opinion that the statement should be rephrased. Two electronic rounds via online survey of iterative rating and feedback were anonymously completed, followed by a final round of in-person meeting during the inaugural International Endoscopic and Robotic Breast Surgery Symposium 2019 from May 24 to 25, 2019. Consensus was reached when there was at least 80% agreement on each statement. RESULTS: A total of 53 statements with at least 80% agreement were generated after 3 rounds of voting; 21 statements from first round of voting, 20 statements from second round of voting and 12 statements from the final round of in-person meeting. All experts agreed that the consensus statement served as expert recommendations but not mandatory for a successful and safe practice of robotic mastectomy. CONCLUSION: Robotic mastectomy is a promising technique and could well be the future of minimally invasive breast surgery whereas proving to be safe and feasible. The first consensus statement on robotic mastectomy from an international panel of experts serves as an extremely important milestone and provides recommendations for breast surgeons keen to embark on this technique.

Liquid Biopsy Detects Relapse Five Months Earlier than Regular Clinical Follow-Up and Guides Targeted Treatment in Breast Cancer.

Genetic alterations in circulating tumor DNA (ctDNA) are an emerging biomarker for the early detection of relapse and have the potential to guide targeted treatment. ctDNA analysis is often performed by droplet digital PCR; however, next-generation sequencing (NGS) allows multigene testing without having to access a tumor sample to identify target alterations. Here, we report the case of a stage III hormone receptor-positive breast cancer patient who remained symptomless after receiving surgery and adjuvant chemotherapy. Liquid biopsy analysis by NGS revealed the presence of a ctDNA PIK3CA N345K mutation five months before the detection of relapse with multiple liver metastases by regular clinical follow-up. To date, clinical implications of the PIK3CA N345K variant remain insufficiently investigated; however, everolimus treatment resulted in the shrinkage of tumor lesions and decreased the levels of tumor markers. Four months after treatment initiation, a second ctDNA analysis suggested a relapse, and the patient clinically progressed after five months of everolimus therapy. This case report demonstrates the value of ctDNA analysis by NGS for the early detection of relapse in breast cancer patients. The study further indicates its usefulness for the choice of targeted treatments, suggesting that the variant PIK3CA N345K might be associated with everolimus sensitivity.

Pazopanib Sensitivity in a Patient With Breast Cancer and FGFR1 Amplification.

Treatment options for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer and resistance to endocrine therapy remain limited. An interesting therapeutic target in these patients is fibroblast growth factor receptor 1 (FGFR1). FGFR1 is amplified in approximately 11% of patients with breast cancer, especially those with HR+ disease. This report presents a patient with metastatic HR+ HER2- breast cancer harboring an FGFR1 amplification who was resistant to endocrine therapy but responded to pazopanib, a multi-tyrosine kinase inhibitor with FGFR-inhibiting activity. Upon pazopanib treatment, the patient's brain lesions nearly disappeared, and she experienced therapeutic changes in the lung and an improvement of liver function. This case suggests that pazopanib may be a promising agent for the treatment of patients with breast cancer and FGFR1 amplifications.

Patient Management with Eribulin in Metastatic Breast Cancer: A Clinical Practice Guide.

Eribulin, an antimicrotubule chemotherapeutic agent, is approved for the treatment of pretreated metastatic breast cancer (mBC) based on the positive outcomes of phase II and phase III clinical trials, which enrolled mainly Western patients. Eribulin has recently been approved in an increasing number of Asian countries; however, there is limited clinical experience in using the drug in certain countries. Therefore, we established an Asian working group to provide practical guidance for eribulin use based on our clinical experience. This paper summarizes the key clinical trials, and the management recommendations for the reported adverse events (AEs) of eribulin in mBC treatment, with an emphasis on those that are relevant to Asian patients, followed by further elaboration of our eribulin clinical experience. It is anticipated that this clinical practice guide will improve the management of AEs resulting from eribulin treatment, which will ensure that patients receive the maximum treatment benefit.

Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer.

Since BRCA mutations are only responsible for 10-20% of cases of breast cancer in patients with early-onset or a family history and since next-generation sequencing technology allows the simultaneous sequencing of a large number of target genes, testing for multiple cancer-predisposing genes is now being considered, but its significance in clinical practice remains unclear. We then developed a sequencing panel containing 68 genes that had cancer risk association for patients with early-onset or familial breast cancer. A total of 133 patients were enrolled and 30 (22.6%) were found to carry germline deleterious mutations, 9 in BRCA1, 11 in BRCA2, 2 in RAD50, 2 in TP53 and one each in ATM, BRIP1, FANCI, MSH2, MUTYH, and RAD51C. Triple-negative breast cancer (TNBC) was associated with the highest mutation rate (45.5%, p = 0.025). Seven of the 9 BRCA1 mutations and the single FANCI mutation were in the TNBC group; 9 of the 11 BRCA2, 1 of the 2 RAD50 as well as BRIP1, MSH2, MUTYH, and RAD51C mutations were in the hormone receptor (HR)(+)Her2(-) group, and the other RAD50, ATM, and TP53 mutations were in the HR(+)Her2(+) group. Mutation carriers were considered as high-risk to develop malignancy and advised to receive cancer screening. Screening protocols of non-BRCA genes were based on their biologic functions; for example, patients carrying RAD51C mutation received a screening protocol similar to that for BRCA, since BRCA and RAD51C are both involved in homologous recombination. In conclusion, we consider that multiple gene sequencing in cancer risk assessment is clinically valuable.

Cancer risk in patients with Graves' disease: a nationwide cohort study.

BACKGROUND: The possibility of an association of Graves' disease (GD) with subsequent cancers has been previously reported. METHODS: Our study used the Taiwanese National Health Insurance Research Database (NHIRD), which identified 5025 newly diagnosed GD patients from 1997 to 2010, and 20,100 frequency matched non-GD patients. The risk of developing cancer for GD patients was measured using the Cox proportional hazard model. RESULTS: The incidence of developing cancer in the GD cohort was 4.92 per 1000 person-years and was 1.37-fold higher than in the comparison cohort (p<0.001). Compared with patients aged 20-34 years, older age groups demonstrated a higher risk of developing cancer (35-49 years: hazard ratio (HR)=4.15; 50-64 years: HR=7.39;≥65 years: HR=13.4). After adjusting for sex, age, and comorbidities, the HR for developing breast cancer and thyroid cancer was 1.58- and 10.4-fold higher for patients with GD. Furthermore, the incidence rates (IRR) were the highest in the first three years: 2.06 [confidence interval (CI)=1.87-2.27] and 15.6 [CI=13.9-17.5] in breast cancer and thyroid cancer with GD respectively. Specifically, a 16-fold hazard of developing thyroid cancer was present in the first three years in the GD cohort compared to the non-GD cohort [CI=7.95-32.1]. CONCLUSIONS: GD patients have a higher risk of cancer, particularly thyroid and breast cancer sequent within six and three years respectively. Strategies for preventing thyroid and breast cancer are proposed.