Faculty Bibliography

BACKGROUND:Nipple-sparing mastectomy (NSM) has become widely available for breast cancer prophylaxis. There are limited data on its long-term oncologic safety. The objective of this study was to determine the incidence of breast cancer in patients who underwent prophylactic NSM. METHODS:All patients undergoing prophylactic NSM at a single institution from 2006 through 2019 were retrospectively reviewed. Patient demographic factors, genetic predispositions, mastectomy specimen pathology, and oncologic occurrences at follow-up were recorded. Descriptive statistics were performed where necessary to classify demographic factors and oncologic characteristics. RESULTS:A total of 871 prophylactic NSMs were performed on 641 patients, with median follow-up of 82.0 months (standard error 1.24). A total of 94.4% of patients ( n = 605) underwent bilateral NSMs, although only the prophylactic mastectomy was considered. The majority of mastectomy specimens (69.6%) had no identifiable pathology. A total of 38 specimens (4.4%) had cancer identified in mastectomy specimens, with ductal carcinoma in situ being the most common (92.1%; n = 35). Multifocal or multicentric disease was observed in seven cases (18.4%) and lymphovascular invasion was identified in two (5.3%). One patient (0.16%), who was a BRCA2 variant carrier, was found to have breast cancer 6.5 years after prophylactic mastectomy. CONCLUSIONS:Overall primary oncologic occurrence rates are very low in high-risk patients undergoing prophylactic NSM. In addition to reducing the risk of oncologic occurrence, prophylactic surgery itself may be therapeutic in a small proportion of patients. Continued surveillance for these patients remains important to assess at longer follow-up intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Risk, IV.

BACKGROUND:Screening MRI as an adjunct to mammography is recommended by the ACS for patients with a lifetime risk for breast cancer > 20%. While the benefits are clear, MRI screening is associated with an increase in false-positive results. The purpose of this study was to analyze our institutional database of high-risk patients and assess the uptake of screening MRI examinations and the results of those screenings. METHODS:Our institutional review board-approved High-Risk Breast Cancer Database was queried for patients enrolled from January 2017 to January 2023 who were at high risk for breast cancer in a comparative analysis between those who were screened versus not screened with MRIs. Variables of interest included risk factor, background, MRI screening uptake, and frequency and results of image-guided breast biopsies. RESULTS:A total of 254 of 1106 high-risk patients (23%) had MRI screening. Forty-six of 852 (5.3%) patients in the non-MRI-screened cohort and nine of 254 (3.5%) patients in the MRI-screened cohort were diagnosed with a malignant lesion after image-guided biopsy (p = 0.6). There was no significant difference between MRI and non-MRI guided biopsies in detecting breast cancer. All malignant lesions were T1 or in situ disease. The 254 patients in the MRI-screened group underwent 185 biopsies. Fifty-seven percent of MRI-guided biopsies yielded benign results. CONCLUSIONS:Although the addition of MRI screening in our high-risk cohort did not produce a significant number of additional cancer diagnoses, patients monitored in our high-risk cohort who developed breast cancer were diagnosed at very early stages of disease, underscoring the benefit of participation in the program.

Background: Prophylactic nipple-sparing mastectomies (NSM) have become increasingly common, although there is little long-Term data on its efficacy in prevention of breast cancer. The objective of this study was to assess the incidence of breast cancer in a cohort of patients undergoing prophylactic NSM with a median follow-up of 10 years. Methods: Patients receiving prophylactic NSM at a single institution from 2006 to 2019 were included in a retrospective nature. Patient demographics, genetic mutations, operative details, and specimen pathology were recorded, and all postoperative patient visits and documentation were screened for cancer occurrence. Descriptive statics were performed where appropriate. Results: Two hundred eighty-four prophylactic NSMs were performed on 228 patients with a median follow-up of 120.5 ± 15.7 months. Roughly, a third of patients had a known genetic mutation, with 21% BRCA1 and 12% BRCA2. The majority (73%) of prophylactic specimens had no abnormal pathology. The most commonly observed pathologies were atypical lobular hyperplasia (10%) and ductal carcinoma in situ (7%). Cancer was identified in 10% of specimens, with only one case of lymphovascular invasion. Thus far, there have been no incidences of locoregional breast cancer occurrence in this cohort. Conclusions: The long-Term breast cancer occurrence rate in this cohort of prophylactic NSM patients at the time of this study is negligible. Despite this, continued surveillance of these patients is necessary until lifetime risk of occurrence following NSM has been established.

Background and Objectives: Perioperative ketamine has been shown to reduce opioid consumption and pain after surgery. Ketamine is most often given as an infusion, but an alternative is single-dose ketamine. Single-dose ketamine at up to 1 mg/kg has been shown to reduce symptoms of depression, and a wide range of dosages has been used for pain in the emergency department. However, limited data exists on the tolerability and efficacy of a single-dose of ketamine at 0.6 mg/kg for pain when administered immediately after surgery. We conducted a pilot study of single-dose ketamine in patients undergoing mastectomy with reconstruction, hypothesizing that a single-dose of ketamine is well tolerated and can relieve postoperative pain and improve mood and recovery. Methods: This is a randomized, single-blind, placebo-controlled, two-arm parallel, single-center study. Thirty adult women undergoing mastectomy with reconstruction for oncologic indication received a single-dose of ketamine (0.6mg/kg) or placebo after surgery in the post-anesthesia care unit (PACU). Patients were followed through postoperative day (POD) 7. The primary outcome was postoperative pain measured by the Brief Pain Inventory (BPI) pain subscale on POD 1 and 2. Secondary outcomes include effects on opioid use, PROMIS fatigue and sleep, mood, Quality of Recovery-15, and the Breast Cancer Pain Questionnaire. Results: Side effects were minor and not significantly different in frequency between groups. The ketamine group reported lower scores on the BPI pain severity subscale, especially at POD 7; however, the difference was not statistically significant. There were no statistically significant differences between ketamine and placebo groups for the secondary outcomes. Conclusion: A single-dose of ketamine at 0.6mg/kg administered postoperatively in the PACU is well tolerated in women undergoing mastectomy and may confer better pain control up to one week after surgery. Future studies with larger sample sizes are necessary to adequately characterize the effect of postoperative single-dose ketamine on pain control in this population.

One to two percent of ectopic parathyroid adenomas are found in the lower mediastinum and often these are best accessed via a sternotomy or thoracotomy. Video-assisted thoracoscopic surgery (VATS) is an alternative approach with less surgical trauma, decreased morbidity, shorter hospital stays, and superior cosmetic results. Ten years after the first VATS resection of an ectopic mediastinal parathyroid, a robot-assisted thoracoscopic approach was described. Here we describe a series of five robot assisted complete thymectomies in patients with primary hyperparathyroidism due to mediastinal ectopic parathyroid adenomas. A single surgeon, single institution case series of five consecutive robotic-assisted mediastinal parathyroidectomies was performed between March 2013 and September 2015. The patients' ages ranged from 31 to 65, 80 % were female, and all had primary hyperparathyroidism due to an ectopic parathyroid located in the lower mediastinum. Pre-operative imaging workup included Technetium 99-sestimibi parathyroid scan and CT scan of the chest. An ectopic parathyroid adenoma was successfully removed in all five cases, with intraoperative iOPTH decreasing ~50 % from baseline after 10 minutes. A hypercellular parathyroid was confirmed on pathologic exam in all specimens. Post-operative discharge and follow up calcium levels all returned to normal. There were no intraoperative complications, including no recurrent laryngeal nerve injuries, no postoperative morbidity, and no mortalities. This case series demonstrates that a robot-assisted complete thymectomy for mediastinal parathyroid adenomas causing primary hyperparathyroidism provides excellent visualization of the mediastinum, is effective at reducing PTH and calcium levels, and is safe with no morbidity or mortality.

Purpose: Well-established risk factors for breast cancer include family history (FH), BRCA mutations and biopsies with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS). Several mathematical models, including the Gail and Tyrer-Cuzick models, have been developed to quantify a patient's risk for developing breast cancer. These models all differ in the list of variables and risk factors that are included in risk calculations. As a result, there is no single model that best estimates the risk for all high risk patients. The purpose of this study is to examine the application of the Gail and Tyrer-Cuzick models in a contemporary cohort of women who are enrolled in a comprehensive high-risk breast cancer database. Methods: The institutional High Risk Breast Cancer Consortium (HRBCC) was established in January 2011. Patients who were at high risk for developing breast cancer based on family history (maternal and paternal), BRCA mutations, AH and LCIS were eligible to enroll in the database. The following variables were included in this analysis: age, family history, genetic testing results, reproductive history, AH, LCIS, Gail and Tyrer-Cuzick scores, risk reduction strategies, and outcomes. All clinical data are obtained from detailed questionnaires filled out by patients who consent to the database studies and from a review of electronic medical records. Descriptive statistics were performed. Results: A total of 604 women were enrolled between 1/2011-2/2016. The median age was 51 years (range 20-87). The majority of women were Caucasian (83%). 52% had a strong FH, 13% were BRCA1 and 2 positive, 48% had AH, and 22% had LCIS. 47% of patients in our high risk program were not eligible for Gail model analysis (age <35 years, BRCA mutation carriers, history of LCIS). Only one patient was not eligible for Tyrer-Cuzick model calculation based on age >84 years. For patients who were eligible for Gail model analysis, 26 (8%) women did not meet criteria (5-year risk >=1.7%) for being designated as high risk for breast cancer. 34 (6%) of our patients did not have Tyrer- Cuzick scores over 20% (criterion for high risk). Notably, majority of the patients (69%) who were not defined as high-risk based on Gail scores >=1.7% or Tyrer-Cuzick scores >=20%, had a strong family history of breast cancer. Only 14 (2%) patients developed breast cancer during our study period, and the majority (93%) of the cancers were early stage (stage 0, I). Conclusions: Our institutional high-risk database includes women who are at high risk based on well-established risk factors for developing breast cancer (FH, BRCA mutations, AH, LCIS). Current mathematical models including the Gail and Tyrer-Cuzick models did not capture the increased risk of breast cancer in 8% of our population. While the models are helpful, in clinical practice they are not necessarily the be-all and end-all. Using heuristic risk factors is more time efficient and comprehensive risk assessment allows the clinicians and patients to better understand risk. Identifying patients as high risk and enrolling them in a high-risk database and program allow us to capture long term follow up, recommend surveillance for early detection, and better understand the effectiveness of different risk reduction and management strategies for this population

PURPOSE: The-Optimal-Lymph-Flow health IT system (TOLF) is a patient-centered, web-and-mobile-based educational and behavioral health IT system focusing on safe, innovative, and pragmatic self-care strategies for lymphedema symptom management. The purpose of this study was to evaluate usability, feasibility, and acceptability of TOLF among the end-user of breast cancer survivors. METHODS: Two types of usability testing were completed with 30 breast cancer survivors: heuristic evaluation and end-user testing. Each participant was asked to think aloud while completing a set of specified tasks designed to explicate and freely explore the system features. A heuristic evaluation checklist, the Perceived Ease of Use and Usefulness Questionnaire, and The Post Study System Usability Questionnaire were used to evaluate usability of the system. Open-ended questions were used to gather qualitative data. Quantitative data were analyzed using descriptive statistics and qualitative data were summarized thematically. RESULTS: Breast cancer survivors were very satisfied with the system: 90% (n = 27) rated the system having no usability problems; 10% (n = 3) noted minor cosmetic problems: spelling errors or text font size. The majority of participants 96.6% (n = 29) strongly agreed that the system was easy to use and effective in helping to learn about lymphedema, symptoms and self-care strategies. Themes from the qualitative data included empowerment, high quality information, loving avatar simulation videos, easy accessibility, and user-friendliness. CONCLUSIONS: This usability study provided evidence on breast cancer survivor's acceptance and highly positive evaluation of TOLF's usability as well as feasibility of using technologically-driven delivery model to enhance self-care strategies for lymphedema symptom management.

BACKGROUND: Many women suffer from daily distressing symptoms related to lymphedema following breast cancer treatment. Lymphedema, an abnormal accumulation of lymph fluid in the ipsilateral body area or upper limb, remains an ongoing major health problem affecting more than 40% of 3.1 million breast cancer survivors in the United States. Patient-centered care related to lymphedema symptom management is often inadequately addressed in clinical research and practice. mHealth plays a significant role in improving self-care, patient-clinician communication, and access to health information. The-Optimal-Lymph-Flow health IT system (TOLF) is a patient-centered, web-and-mobile-based educational and behavioral mHealth interventions focusing on safe, innovative, and pragmatic electronic assessment and self-care strategies for lymphedema symptom management. The purpose of this paper is to describe the development and test of TOLF system. METHODS: The development of TOLF was guided by the Model of Self-Care for Lymphedema Symptom Management and designed based on principles fostering accessibility, convenience, and efficiency of mHealth system to enhance training and motivating assessment of and self-care for lymphedema symptoms. Test of TOLF was accomplished by conducting a psychometric study to evaluate reliability, validity, and efficiency of the electronic version of Breast Cancer and Lymphedema Symptom Experience Index (BCLE-SEI), a usability testing and a pilot feasibility testing of mHealth self-care interventions. RESULTS: Findings from the psychometric study with 355 breast cancer survivors demonstrated high internal consistency of the electronic version of the instrument: a Cronbach's alpha coefficient of 0.959 for the total scale, 0.919 for symptom occurrence, and 0.946 for symptom distress. Discriminant validity of the instrument was supported by a significant difference in symptom occurrence (z=-6.938, P<0.000), symptom distress (z=-5.894, P<0.000), and total scale (z=-6.547, P<0.000) between breast cancer survivors with lymphedema and those without it. Findings of usability testing showed that breast cancer survivors were very satisfied with the mHealth self-care interventions: 90% rated the system having no usability problems; 10% noted minor cosmetic problems: spelling errors or text font size. The majority of participants 96.6% strongly agreed that the system was easy to use and effective in helping to learn about lymphedema, symptoms and self-care strategies. Feasibility testing demonstrated that a 12-week one group intervention using TOLF had significantly positive effects on less pain (P=0.031), less soreness (P=0.021), less aching (P=0.024), less tenderness (P=0.039), fewer numbers of lymphedema symptoms (P=0.003), and improved symptom distress (P=0.000) at 12 weeks after intervention. Themes from the qualitative data included empowerment, high quality information, loving avatar simulation videos, easy accessibility, and user-friendliness. CONCLUSIONS: TOLF system using the electronic version of the instrument is able to assess patients' lymphedema symptoms with high reliability and validity. TOLF system is also able to deliver self-care interventions to enhance self-care strategies for lymphedema symptom management.

BACKGROUND: Despite current advances in cancer treatment, many breast cancer survivors still face long-term post-operative challenges as a result of suffering from daily pain and other distressing symptoms related to lymphedema, ie, abnormal accumulation of lymph fluid in the ipsilateral upper limb or body. Grounded in research-driven behavioral strategies, The-Optimal-Lymph-Flow is a unique Web- and mobile-based system focusing on self-care strategies to empower, rather than inhibit, how breast cancer survivors manage daily pain and symptoms. It features a set of safe, feasible, and easily-integrated-into-daily-routine exercises to promote lymph flow and drainage, as well as guidance to maintain an optimal body mass index (BMI). OBJECTIVE: To conduct a randomized clinical trial (RCT) to evaluate the efficacy of the Web- and mobile-based The-Optimal-Lymph-Flow system for managing chronic pain and symptoms related to lymphedema. The primary outcome includes pain reduction, and the secondary outcomes focus on symptom relief, limb volume difference by infra-red perometer, BMI, and quality of life (QOL) related to pain. We hypothesize that participants in the intervention group will have improved pain and symptom experiences, limb volume difference, body mass index, and QOL. METHODS: A parallel RCT with a control-experimental, pre- and post-test, repeated-measures design is used in this study. A total of 120 patients will be randomized according to the occurrence of pain. Participants will be recruited face-to-face at the point of care during clinical visits. Participants in the intervention group will receive the Web- and mobile-based The-Optimal-Lymph-Flow intervention and will have access to and learn about the program during the first in-person research visit. Participants in the control group will receive the Web- and mobile-based Arm Precaution program and will have access to and learn about the program during the first in-person research visit. Participants will be encouraged to enhance their learning by accessing the program and following the daily exercises during the study period. Participants will have monthly online self-report of pain and symptoms at 4 and 8 weeks post-intervention. During the two in-person research visits prior to and 12 weeks post-intervention, participants will be measured for limb volume difference, BMI, and complete self-report of pain, symptoms, self-care behaviors, and QOL. RESULTS: This trial is currently open for recruitment. The anticipated completion date for the study is July 2017. The primary endpoint for the study is absence or reduction of pain reported by the participants at week 12 post-intervention. CONCLUSIONS: The-Optimal-Lymph-Flow is a unique Web- and mobile-based self-care and patient-reported outcome system designed to effectively help women treated for breast cancer manage daily pain and symptoms related to lymphedema. Patients learn self-care strategies from a Web- and mobile-based program and track their symptoms. The RCT will directly benefit all women treated for breast cancer who suffer from or at risk for pain and symptoms related to lymph fluid accumulation. TRIAL REGISTRATION: Clinicaltrials.gov NCT02462226; https://clinicaltrials.gov/ct2/show/NCT02462226 (Archived by WebCite at http://www.webcitation.org/6du4IupG5).