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Margin Assessment and Re-excision Rates for Patients Who Have Neoadjuvant Chemotherapy and Breast-Conserving Surgery

Cen, Cindy; Chun, Jennifer; Kaplowitz, Elianna; Axelrod, Deborah; Shapiro, Richard; Guth, Amber; Schnabel, Freya
BACKGROUND:Neoadjuvant chemotherapy (NAC) has enabled more patients to be eligible for breast-conservation surgery (BCS). Achieving negative lumpectomy margins, however, is challenging due to changes in tissue composition and potentially scattered residual carcinoma in the tumor bed. Data regarding BCS after NAC have shown variable re-excision rates. MarginProbe (Dilon Technologies, Newport News, VA, USA) has been shown to identify positive resection margins intraoperatively and to reduce the number of re-excisions in primary BCS, but has not been studied in NAC+BCS cases. This study aimed to investigate the clinicopathologic characteristics, margin status, and re-excision rates for NAC+BCS patients with and without the use of MarginProbe. METHODS:The Institutional Breast Cancer Database was queried for patients who received NAC and had BCS from 2010 to 2019. The variables of interest were demographics, tumor characteristics, pathologic complete response (pCR), MarginProbe use, and re-excision rates. RESULTS:The study population consisted of 214 patients who had NAC, 61 (28.5 %) of whom had NAC+BCS. The median age of the patients was 53.5 years. A pCR was achieved for 19 of the patients (31.1 %). Of the remaining 42 patients, 9 (21 %) had close or positive margins that required re-excision. Re-excision was associated with a larger residual tumor size (p = 0.025) and estrogen receptor (ER)-positive disease before NAC (p = 0.041). MarginProbe use was associated with a lower re-excision rate for the patients who had NAC+BCS (6 % vs. 31 %, respectively). CONCLUSION/CONCLUSIONS:The patients with a larger residual tumor burden and ER-positive disease had a greater risk for inadequate margins at surgery. MarginProbe use was associated with a lower re-excision rate. Techniques to reduce the need for re-excision will support the use of BCS after NAC.
PMID: 33635409
ISSN: 1534-4681
CID: 4802382

The Effects of Obesity on Lymphatic Pain and Swelling in Breast Cancer Patients

Fu, Mei Rosemary; Axelrod, Deborah; Guth, Amber; McTernan, Melissa L; Qiu, Jeanna M; Zhou, Zhuzhu; Ko, Eunjung; Magny-Normilus, Cherlie; Scagliola, Joan; Wang, Yao
Lymphatic pain and swelling due to lymph fluid accumulation are the most common and debilitating long-term adverse effects of cancer treatment. This study aimed to quantify the effects of obesity on lymphatic pain, arm, and truncal swelling. Methods: A sample of 554 breast cancer patients were enrolled in the study. Body mass index (BMI), body fat percentage, and body fat mass were measured using a bioimpedance device. Obesity was defined as a BMI ≥ 30 kg/m2. The Breast Cancer and Lymphedema Symptom Experience Index was used to measure lymphatic pain, arm, and truncal swelling. Multivariable logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (CI) to quantify the effects of obesity. Results: Controlling for clinical and demographic characteristics as well as body fat percentage, obesity had the greatest effects on lymphatic pain (OR 3.49, 95% CI 1.87-6.50; p < 0.001) and arm swelling (OR 3.98, 95% CI 1.82-4.43; p < 0.001). Conclusions: Obesity is a significant risk factor for lymphatic pain and arm swelling in breast cancer patients. Obesity, lymphatic pain, and swelling are inflammatory conditions. Future study should explore the inflammatory pathways and understand the molecular mechanisms to find a cure.
PMID: 34356882
ISSN: 2227-9059
CID: 5006032

Multinuclear MRI to disentangle intracellular sodium concentration and extracellular volume fraction in breast cancer

Ianniello, Carlotta; Moy, Linda; Fogarty, Justin; Schnabel, Freya; Adams, Sylvia; Axelrod, Deborah; Axel, Leon; Brown, Ryan; Madelin, Guillaume
The purpose of this work was to develop a novel method to disentangle the intra- and extracellular components of the total sodium concentration (TSC) in breast cancer from a combination of proton ([Formula: see text]H) and sodium ([Formula: see text]) magnetic resonance imaging (MRI) measurements. To do so, TSC is expressed as function of the intracellular sodium concentration ([Formula: see text]), extracellular volume fraction (ECV) and the water fraction (WF) based on a three-compartment model of the tissue. TSC is measured from [Formula: see text] MRI, ECV is calculated from baseline and post-contrast [Formula: see text]H [Formula: see text] maps, while WF is measured with a [Formula: see text]H chemical shift technique. [Formula: see text] is then extrapolated from the model. Proof-of-concept was demonstrated in three healthy subjects and two patients with triple negative breast cancer. In both patients, TSC was two to threefold higher in the tumor than in normal tissue. This alteration mainly resulted from increased [Formula: see text] ([Formula: see text] 30 mM), which was [Formula: see text] 130% greater than in healthy conditions (10-15 mM) while the ECV was within the expected range of physiological values (0.2-0.25). Multinuclear MRI shows promise for disentangling [Formula: see text] and ECV by taking advantage of complementary [Formula: see text]H and [Formula: see text] measurements.
PMID: 33664340
ISSN: 2045-2322
CID: 4801862

The Microbiome and Metabolome of Malignant Fungating Wounds: A Systematic Review of the Literature From 1995 to 2020

Tilley, Charles P; Fu, Mei R; Qiu, Jeanna M; Comfort, Christopher; Crocilla, Brooke L; Li, Zujun; Axelrod, Deborah
PURPOSE/OBJECTIVE:Malignant fungating wounds (MFWs) afflict up to 14% of patients with advanced cancer. The bacterial community structures of MFW may influence the development and severity of wound symptoms. The purpose of this systematic review was to evaluate existing evidence regarding the relationship between microbiome and symptoms of MFWs. METHODS:A systematic review of the published literature from January 1995 to January 2020 was conducted. An established quality assessment tool was used to assess the quality of the included studies. SEARCH STRATEGY/METHODS:We searched 4 major electronic databases and retrieved 724 articles; 7 met inclusion criteria. FINDINGS/CONCLUSIONS/CONCLUSIONS:Seven studies were included; the overall quality of the included 7 studies was ranked as adequate. Findings from the studies provided an incomplete characterization of the microbiome and metabolome of MFW; none included modern genomic technologies. Twenty different species of aerobes and 14 species of anaerobes were identified, with inconsistent identification of biofilms and multi-drug-resistant bacteria. Symptom occurrence increased with the number of bacteria species (P = .0003) and the presence of at least 1 anaerobe (P = .0006) in malignant wound beds. Cancer wound-derived odor was associated with dimethyl trisulfide and 4 fatty acid volatiles. Periwound and moisture-associated skin damage were associated with higher putrescine levels in exudates. IMPLICATIONS/CONCLUSIONS:Understanding the role of microbiota of MFW in developing or amplifying the severity of wound symptoms is the first step toward development of more precise and effective topical interventions.
PMID: 33690246
ISSN: 1528-3976
CID: 4827182

Model-Based Patterns of Lymphedema Symptomatology: Phenotypic and Biomarker Characterization

Fu, Mei R; Aouizerat, Bradley E; Yu, Gary; Conley, Yvette; Axelrod, Deborah; Guth, Amber A; Gagner, Jean-Pierre; Qiu, Jeanna M; Zagzag, David
Purpose of the Study/UNASSIGNED:More than 50% of breast cancer survivors without a diagnosis of lymphedema suffer daily from numerous and co-occurring lymphedema symptoms. This study aimed to identify lymphedema symptom patterns and the association of such patterns with phenotypic characteristics and biomarkers using latent class analysis (LCA). A prospective, descriptive, and repeated-measure design was used to enroll 140 women and collect data. Recent Findings/UNASSIGNED:LCA identified three distinct lymphedema symptom classes at 8 weeks and 12 months post-surgery: low, moderate, and severe symptom classes and associated phenotypic characteristics. Participants were more likely to be in the severe symptom classes at 12 months post-surgery if they had lower education level, cording, an axillary syndrome at 8 weeks post-surgery, neoadjuvant chemotherapy, and radiation. Summary/UNASSIGNED:Pre-surgery level of IL1-a, IL-6, IL-8, and VEGF was associated with the severe symptom class at 8 weeks post-surgery, suggesting that such biomarkers may be used to predict risk for lymphedema symptoms.
PMID: 34322193
ISSN: 1943-4588
CID: 4949832

Oncologic Considerations for Safe Gender-Affirming Mastectomy: Preoperative Imaging, Pathologic Evaluation, Counseling, and Long-Term Screening

Salibian, Ara A; Axelrod, Deborah M; Smith, Julia A; Fischer, Beverly A; Agarwal, Cori; Bluebond-Langner, Rachel
SUMMARY/CONCLUSIONS:There remain significant gaps in the evidence-based care of patients undergoing gender-affirming mastectomy with regard to implications for breast cancer development and screening. The current clinical evidence does not demonstrate an increased risk of breast cancer secondary to testosterone therapy in transgender patients. Gender-affirmation mastectomy techniques vary significantly with regard to the amount of residual breast tissue left behind, which has unknown implications for the incidence of postoperative breast cancer and need for screening. Subcutaneous mastectomy should aim to remove all gross breast parenchyma, although this is limited in certain techniques. Tissue specimens should also be routinely sent for pathologic analysis. Several cases of incidental breast cancer after subcutaneous mastectomy have been described. There is little evidence on the need for or types of postoperative cancer screening. Chest awareness is an important concept for patients that have undergone subcutaneous mastectomies, as clinical examination remains the most common reported method of postmastectomy malignancy detection. In patients with greater known retained breast tissue, such as those with circumareolar or pedicled techniques, consideration may be given to alternative imaging modalities, although the efficacy and cost-utility of these techniques must still be proven. Preoperative patient counseling on the risk of breast cancer after gender-affirming mastectomy in addition to the unknown implications of residual breast tissue and long-term androgen exposure is critical. Patient awareness and education play an important role in shared decision-making, as further research is needed to define standards of medical and oncologic care in this population.
PMID: 33565823
ISSN: 1529-4242
CID: 4806412

The Effects of Kinect-Enhanced Lymphatic Exercise Intervention on Lymphatic Pain, Swelling, and Lymph Fluid Level

Fu, Mei R; McTernan, Melissa L; Qiu, Jeanna M; Ko, Eunjung; Yazicioglu, Simay; Axelrod, Deborah; Guth, Amber; Fan, Zhipeng; Sang, Anna; Miaskowski, Christine; Wang, Yao
BACKGROUND/UNASSIGNED: OBJECTIVES/UNASSIGNED:This feasibility trial aimed to determine the feasibility, usability, and effects of the Kinect-TOLF on lymphatic pain, swelling, lymphedema symptoms, and lymph fluid levels. METHODS/UNASSIGNED:were performed for data analysis. Qualitative data were assessed for common themes. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:The Kinect-TOLF is safe, feasible, and effective in reducing lymphatic pain, swelling, lymphedema symptoms, and in decreasing lymph fluid levels. Future research should focus on a randomized clinical trial to confirm the unique or synergistic efficacy of the Kinect-TOLF in comparison with current lymphedema treatment and other forms of exercises or movement therapy. This study was registered in with US Identifier: NCT03999177.
PMID: 34160294
ISSN: 1552-695x
CID: 4929142

Real-time electronic patient evaluation of lymphedema symptoms, referral, and satisfaction: a cross-sectional study

Nahum, Jennifer L; Fu, Mei R; Scagliola, Joan; Rodorigo, Martha; Tobik, Sandy; Guth, Amber; Axelrod, Deborah
Background/UNASSIGNED:Lymphedema is a progressive and chronic illness. Early detection and treatment often lead to better clinical outcomes and improvement of patients' quality of life. Lymphedema symptoms can assist in detecting lymphedema. However, the use of patient-reported symptom evaluation is still limited in clinical practice. To address this gap in clinical practice, a metropolitan cancer center implemented an electronic patient evaluation of lymphedema symptoms (EPE-LE) to enable patients' real-time symptom report during patients' routine clinical visit while waiting to see their doctors in a waiting room. The purpose of this clinical project was to evaluate the usefulness of EPE-LE during patients' routine clinical visit. Methods/UNASSIGNED:A cross-sectional design was used. Participants were outpatient post-surgical breast cancer patients and clinicians who were involved in the EPE-LE implementation at a metropolitan cancer center of US. Data were collected during the three-month EPE-LE implementation, including patients' report of lymphedema symptoms, patient and clinician satisfaction, and referral to lymphedema specialists. Descriptive statistics were used for data analysis. Results/UNASSIGNED:During the three-month implementation, a total of 334 patients utilized the EPE-LE to report their lymphedema symptoms and 24 referrals to lymphedema specialists. Nearly all of the patients found that the EPE-LE was easy to use (91%) and that they were satisfied with the EPE-LE for reporting lymphedema symptoms (89%). The majority (70%) of patients reported that the EPE-LE helped them to learn about symptoms related to lymphedema and encouraged them to monitor their symptoms. All clinicians (100%) agreed that the use of the EPE-LE improved their lymphedema symptom assessment in post-surgical breast cancer patients; 75% reported that the EPE-LE increased their communication with patients related to lymphedema symptoms, 75% agreed they would recommend the EPE-LE for use at other cancer centers, and 75% reported that the information retrieved from the EPE-LE was helpful in evaluation of lymphedema. Conclusions/UNASSIGNED:The use of EPE-LE enhanced patients' real-time report of lymphedema symptoms, improved patient education on lymphedema symptoms, and helped clinicians for evaluation of lymphedema. The use of EPE-LE is an example how to implement evidence-based research into clinical practice that provides benefits for both patients and clinicians.
PMID: 33898589
ISSN: 2306-9740
CID: 5005732

Sentinel lymph node positivity in patients undergoing mastectomies for ductal carcinoma in situ (DCIS)

Price, Alison; Schnabel, Freya; Chun, Jennifer; Kaplowitz, Elianna; Goodgal, Jenny; Guth, Amber; Axelrod, Deborah; Shapiro, Richard; Mema, Eralda; Moy, Linda; Darvishian, Farbod; Roses, Daniel
Current guidelines recommend sentinel lymph node biopsy (SLNB) for patients undergoing mastectomy for a preoperative diagnosis of ductal carcinoma in situ (DCIS). We examined the factors associated with sentinel lymph node positivity for patients undergoing mastectomy for a diagnosis of DCIS on preoperative core biopsy (PCB). The Institutional Breast Cancer Database was queried for patients with PCB demonstrating pure DCIS followed by mastectomy and SLNB from 2010 to 2018. Patients were divided according to final pathology (DCIS or invasive cancer). Clinico-pathologic variables were analyzed using Pearson's chi-squared, Wilcoxon Rank-Sum and logistic regression. Of 3145 patients, 168(5%) had pure DCIS on PCB and underwent mastectomy with SLNB. On final mastectomy pathology, 120(71%) patients had DCIS with 0 positive sentinel lymph nodes (PSLNs) and 48(29%) patients had invasive carcinoma with 5(10%) cases of ≥1 PSLNs. Factors positively associated with upstaging to invasive cancer in univariate analysis included age (P = .0289), palpability (P < .0001), extent of disease on imaging (P = .0121), mass on preoperative imaging (P = .0003), multifocality (P = .0231) and multicentricity (P = .0395). In multivariate analysis, palpability (P = .0080), extent of disease on imaging (P = .0074) and mass on preoperative imaging (P = .0245) remained significant (Table 2). In a subset of patients undergoing mastectomy for DCIS with limited disease on preoperative evaluation, SLNB may be omitted as the risk of upstaging is low. However, patients who present with clinical findings of palpability, large extent of disease on imaging and mass on preoperative imaging have a meaningful risk of upstaging to invasive cancer, and SLNB remains important for management.
PMID: 31957944
ISSN: 1524-4741
CID: 4272692

Pregnancy-associated breast cancer in a contemporary cohort of newly diagnosed women

Gooch, Jessica C; Chun, Jennifer; Kaplowitz, Elianna; Guth, Amber; Axelrod, Deborah; Shapiro, Richard; Roses, Daniel; Schnabel, Freya
Pregnancy-associated breast cancer (PABC) refers to breast cancer (BC) diagnosed during pregnancy, lactation, or in the postpartum period. There is evidence that PABC is associated with a poorer prognosis, and that the development of the disease is influenced by the unique hormonal milieu of pregnancy. The purpose of this study was to investigate the clinicopathologic characteristics associated with PABC in a contemporary cohort of women with newly diagnosed BC. Our institutional Breast Cancer Database was queried for women diagnosed with BC between 2009-2018 who had at least one full-term pregnancy (FTP). Variables of interest included patient demographics and clinical and tumor characteristics. PABC was defined as breast cancer diagnosed within 24 months of delivery. Statistical analyses included Pearson's chi-square and logistic regression. Out of a total of 2202 women, 46 (2.1%) had PABC. Median follow-up in the total cohort was 5.5 years. After adjusting for age at first FTP, PABC was associated with younger age at diagnosis, older age at first FTP, non-Caucasian race, BRCA positivity, presentation with a palpable mass, higher pathologic stage, higher histologic grade, and ER-negative and triple-negative receptor status. The association of PABC with non-Caucasian race may be reflected in the increased proportion of triple-negative breast cancers in the PABC group. PABC was also associated with older age at first FTP. As more women delay childbearing, risk for PABC may increase. Our findings suggest that women who become pregnant at older ages should be followed carefully during pregnancy and the postpartum period, especially if they are BRCA mutation carriers. The optimal approach for monitoring older women during pregnancy and the postpartum period is unclear.
PMID: 31448522
ISSN: 1524-4741
CID: 4054182