Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria.

As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.

Correction: Pandey et al. ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer. Cancers 2019, 11, 718.

In the original publication [...].

Analysis of the Understanding and Worry about Lymphedema of Patients with Breast Cancer.

BACKGROUND: Lymphedema is a potential lifelong sequela of breast cancer treatment. We sought to: (1) evaluate the worry and knowledge of patients about lymphedema, (2) quantify patients reporting lymphedema education and screening, and (3) determine willingness to participate in lymphedema screening and prevention programs. PATIENTS AND METHODS: A survey evaluating lymphedema-related knowledge and worry was sent to patients treated for stage 0-III breast cancer. Exclusion criteria included > 10 years since diagnosis, missing clinical staging, and those without axillary surgery. Responses were linked with clinicopathologic information. RESULTS: Of 141 patients meeting inclusion criteria, 89% of those without lymphedema were not at all or slightly worried about lymphedema. Higher levels of worry were associated with clinical stage II-III disease [odds ratio (OR) 2.63, p = 0.03], a history of axillary lymph node dissection (ALND) (OR 4.58, p < 0.01), and employment (OR 2.21, p = 0.05). A total of 102 (72%) patients recalled receiving lymphedema education. Lymphedema knowledge was limited, with < 25% of respondents answering > 50% of the risk factor questions correctly. Worry and knowledge were not significantly associated. Of patients without lymphedema, 36% were interested in learning more about lymphedema and 64% were willing to participate in or learn more about a screening program. Most (66%) felt that lymphedema information should be provided before and after cancer treatment. DISCUSSION: A majority of our breast cancer survivors had limited knowledge about lymphedema risk factors. While most patients were not worried about developing lymphedema, higher worry was seen in patients with a higher clinical stage at diagnosis, ALND, and employment. Our findings suggest potential targets and timing for patient-centered educational interventions.

Influence of endocrine multidisciplinary tumor board on patient management and treatment decision making.

BACKGROUND: Multidisciplinary Tumor Boards (MDT) are used to obtain input regarding cancer management. This study assessed the impact of our institutional Endocrine MDT. METHODS: MDT notes on patients with thyroid cancer treated during 2012-2018 were abstracted retrospectively from the electronic medical record. Management change (MC) was prospectively collected by the MDT coordinator. Biannual evaluations reviewed the impact of the MDT as observed by attendees. RESULTS: MC was recommended in 47 (15%) of 286 presentations, with additional imaging being the most frequent (43%). Presentation of recurrences were more likely to result in MC (24% vs. 13% initial, p = 0.03). Overall, 98% of attendees found the conference exceeded educational expectations. About 24% reported intending to use a more evidence/guideline-based approach after attending and this trend increased over time (p = 0.002). CONCLUSION: MDT presentations led to a higher rate of MC particularly in recurrent TC patients and increased evidenced-based practice for attendees.

Endocrine surgeons have high rates of work-related musculoskeletal (MSK) injury and symptoms.

BACKGROUND: Work-related injury and musculoskeletal (MSK) symptoms are common among surgeons, however data for endocrine surgeons (ES) are lacking. METHODS: A survey was distributed to American Association of Endocrine Surgeons (AAES) and Endocrine section of American Head and Neck Society (AHNS) members. RESULTS: MSK symptoms were present in 199 (90%) of 220 respondents, most notably pain (91%) and stiffness (81%). The most common locations were neck (87%) and shoulders (55%). Women were more likely to be symptomatic (98.6% versus 86.4%, p = 0.004). Although 67% of respondents reported awareness of ergonomic principles, only 19% had learned about them during training. The most common ergonomic adjustments were stretching, use of microbreaks and headlight/loupe adjustments. CONCLUSION: The vast majority of ES surgeons suffer MSK symptoms that could potentially impact their quality of life and career length. Effective strategies are needed to protect this highly trained workforce.

Risk management recommendations and patient acceptance vary with high-risk breast lesions.

INTRODUCTION: Lobular carcinoma in situ (LCIS), atypical ductal and lobular hyperplasia (AH) increase breast cancer risk. We examined risk management recommendations (RMR) and acceptance in AH/LCIS. METHODS: All patients with AH/LCIS on core needle biopsy from 2013 to 2016 at our institution were identified; cancer patients were excluded. Univariate and multivariate analysis examined factors associated with management. RESULTS: 98 % of patients were evaluated by breast surgeons and 53 % underwent risk model calculation (RC). 77 % had new RMR. RMR of MRI screening (MRI), genetic counselling (GC) and medical oncology (MO) referral were 41 %, 18 %, 77 %, respectively. MRI screening was more likely recommended in those with strong family history (p = 0.01), and high RC (p < 0.001). Uptake of at least one RMR did not occur in 84 % of patients. Use of RC correlated with MO acceptance (p = 0.049). CONCLUSIONS: Diagnosis of atypia has the potential to change risk management for most, however only 16 % of patients accepted all RMR.

Expression of cancer stem cell markers in tall cell variant papillary thyroid cancer identifies a molecular profile predictive of recurrence in classic papillary thyroid cancer.

BACKGROUND: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. METHODS: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. RESULTS: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). CONCLUSION: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.

Directed movement toward, translocation along, penetration into and exit from vascular networks by breast cancer cells in 3D.

We developed a computer-assisted platform using laser scanning confocal microscopy to 3D reconstruct in real-time interactions between metastatic breast cancer cells and human umbilical vein endothelial cells (HUVECs). We demonstrate that MB-231 cancer cells migrate toward HUVEC networks, facilitated by filopodia, migrate along the network surfaces, penetrate into and migrate within the HUVEC networks, exit and continue migrating along network surfaces. The system is highly amenable to 3D reconstruction and computational analyses, and assessments of the effects of potential anti-metastasis monoclonal antibodies and other drugs. We demonstrate that an anti-RHAMM antibody blocks filopodium formation and all of the behaviors that we found take place between MB-231 cells and HUVEC networks.

Surgical Decision-Making Surrounding Contralateral Prophylactic Mastectomy: Comparison of Treatment Goals, Preferences, and Psychosocial Outcomes from a Multicenter Survey of Breast Cancer Patients.

BACKGROUND: Differences in patient characteristics and decision-making preferences have been described between those who elect breast-conserving surgery (BCS), unilateral mastectomy (UM), or contralateral prophylactic mastectomy (CPM) for breast cancer. However, it is not known whether preferred and actual decision-making roles differ across these surgery types, or whether surgery choice reflects a woman's goals or achieves desired outcomes. METHODS: Women diagnosed with stage 0-III unilateral breast cancer across eight large medical centers responded to a mailed questionnaire regarding treatment decision-making goals, roles, and outcomes. These data were linked to electronic medical records. Differences were assessed using descriptive analyses and logistic regression. RESULTS: There were 750 study participants: 60.1% BCS, 17.9% UM, and 22.0% CPM. On multivariate analysis, reducing worry about recurrence was a more important goal for surgery in the CPM group than the others. Although women's preferred role in the treatment decision did not differ by surgery, the CPM group was more likely to report taking a more-active-than-preferred role than the BCS group. On multivariate analysis that included receipt of additional surgery, posttreatment worry about both ipsilateral and contralateral recurrence was higher in the BCS group than the CPM group (both p < 0.001). The UM group was more worried than the CPM group about contralateral recurrence only (p < 0.001). CONCLUSIONS: Women with CPM were more likely to report being able to reduce worry about recurrence as a very important goal for surgery. They were also the least worried about ipsilateral breast recurrence and contralateral breast cancer almost two years postdiagnosis.

A Pilot Study of Preoperative Vandetanib on Markers of Proliferation and Apoptosis in Breast Cancer.

INTRODUCTION: Preclinical data supports antitumor activity of tyrosine kinase inhibitor vandetanib with Ret as the therapeutic target in breast cancer. We investigated the effect of preoperative vandetanib on markers of proliferation and apoptosis in breast cancer. METHODS: Patients with invasive breast cancer were randomly assigned vandetanib 300 mg or placebo PO daily for 2 weeks before operative resection from January 2014 to June 2017. Pretreatment and posttreatment specimens were analyzed by immunohistochemistry for Ki-67, TUNEL, and p-ERK with stratification by Ret expression by immunohistochemistry. RESULTS: Ten patients were enrolled. There was no statistically significant difference in ERK activation compared with placebo (P=0.45); however, ERK activation was reduced 74% compared with pretreatment biopsy with vandetinib treatment (P=0.005) without a significant reduction in the placebo group (-29%, P=0.55). Mean change in Ki-67 after vandetanib treatment was +0.3% compared with +2.0% in placebo treated patients, P=0.72. Mean change in TUNEL was +0.48 apoptotic nuclei per HPF in the vandetanib arm compared with +1.02 in the placebo arm, P=0.32. In vandetanib treated patients, Ki-67 was reduced 0.3% in RET-positive tumors compared with increased 1.0% in RET-negative tumors, P=0.43 and TUNEL was increased 0.77 in RET-positive tumors and 0.2 in RET-negative tumors, P=0.21. CONCLUSIONS: In this pilot study, no statistically significant differences on prespecified markers were seen with vandetanib compared with placebo. In accordance with the investigational hypothesis, there was a nonsignificant trend with vandetanib treatment of reduction in p-ERK and increased effects in Ret expressing tumors.

Impact of age, rurality and distance in predicting contralateral prophylactic mastectomy for breast cancer in a Midwestern state: a population-based study.

PURPOSE: Iowa is among several rural Midwestern states with the highest proportions of contralateral prophylactic mastectomy (CPM) in women < 45 years of age. We evaluated the role of rurality and travel distance in these surgical patterns. METHODS: Women with unilateral breast cancer (2007-2017) were identified using Iowa Cancer Registry records. Patients and treating hospitals were classified as metro, nonmetro, and rural based on Rural-Urban Continuum Codes. Differences in patient, tumor, and treatment characteristics and median travel distance (MTD) were compared. Characteristics associated with CPM were evaluated with multivariate logistic regression. RESULTS: 22,158 women were identified: 57% metro, 26% nonmetro and 18% rural. Young rural women had the highest proportion of CPM (52%, 39% and 40% for rural, metro, nonmetro women < 40 years). Half of all rural women had surgery at metro hospitals; these women had the longest MTD (62 miles). Among all women treated at metro hospitals, rural women had the highest proportion of CPM (17% rural vs 14% metro/nonmetro, p = 0.007). On multivariate analysis, traveling ≥ 50 miles (ORs 1.43-2.34) and rural residence (OR = 1.29) were independently predictive of CPM. Other risk factors were young age (< 40 years: OR = 7.28, 95% CI 5.97-8.88) and surgery at a metro hospital that offers reconstruction (OR = 2.30, 95% CI 1.65-3.21) and is not NCI-designated (OR = 2.34, 95% CI 1.92-2.86). CONCLUSION: There is an unexpectedly high proportion of CPM in young rural women in Iowa, and travel distance and availability of reconstructive services likely influence decision-making. Improving access to multidisciplinary care in rural states may help optimize decision-making.

Racial disparities in comorbid conditions among patients undergoing thyroidectomy for Graves' disease: An ACS-NSQIP analysis.

BACKGROUND: Studies indicate that racial disparities exist in the presentation and outcomes of patients undergoing thyroidectomy for cancer and benign disease. We examined the relationship between race, pre-operative characteristics and outcomes in patients undergoing thyroidectomy for GD. METHODS: Patients were identified from the 2013-2016 American College of Surgeons NSQIP database using ICD-9/10 codes consistent with diffuse toxic goiter. RESULTS: AA patients were more likely to have an ASA classification of ≥3 (41% vs 30%, p < 0.001), a higher rate of CHF (2.1% vs 0.5%, p = 0.01), hypertension (46% vs 32%, p < 0.001) and dyspnea (10% vs 5%, p < 0.001) compared to Non-Hispanic Caucasians (NH-C) patients. Complications were higher in patients with ASA≥3 and CHF but not affected by race. CONCLUSIONS: Analysis of a national database of thyroidectomy for GD revealed a higher burden of preoperative comorbidities in AA patients compared to other races, although race was not an independent predictor of outcomes.

Incorporating Surgical Ergonomics Education into Surgical Residency Curriculum.

BACKGROUND: Education on surgical ergonomics during residency training is lacking. This study aimed to determine the feasibility and impact of incorporating surgical ergonomics lectures into residency curriculum. METHODS: A survey was distributed to 42 residents with questions regarding demographics, surgical factors, prevalence of musculoskeletal (MSK) symptoms, and awareness of ergonomic recommendations. The residents then received 2 lectures on ergonomics in surgery. A follow up survey was distributed to evaluate the impact of the lectures. RESULTS: Twenty-two residents completed the presession survey. Ninety-one percent reported MSK symptoms attributed to their training. Seventeen residents completed the follow up survey. All reported increased awareness of their own habits while operating and improved understanding of methods to prevent and/or treat work-related injuries. All residents recommended incorporating the lectures as an adjunct to their regular curriculum. CONCLUSIONS: The rates of MSK symptoms and/or injury are high among surgeon trainees. Residency is an opportune time to educate on principles of ergonomics and may prevent future injuries.

Evaluation of switch from satellite laboratory to central laboratory for testing of intraoperative parathyroid hormone.

OBJECTIVES: The aim of this study was to evaluate testing turnaround time (TAT) and incision to close time in parathyroid surgeries before and after switching intraoperative parathyroid hormone (PTH) testing from a near point of care location to a central clinical laboratory. DESIGN AND METHODS: This retrospective study covered a ten-year period. Both testing locations used the same Roche Diagnostics PTH immunoassay but on different analyzers. The predominant site for surgeries was the main operating rooms (ORs) in an adjacent building, with a limited number of parathyroid surgeries performed at a more distant ambulatory surgery center (ASC). Under ideal conditions, TAT for near point-of-care testing was 20 â€‹min, although multiple factors could increase TAT. Incision to close time from the electronic health record was used to define time of surgery. RESULTS: A total of 897 unique patients were identified for which 3031 orders for intraoperative PTH were placed (383 unique patients and 1244 orders after switch in testing site). The average total TAT times for testing (mean â€‹± â€‹SD) in the central laboratory were 23.9 â€‹± â€‹16.0 â€‹min (median, 22 â€‹min) for all specimens, 22.8 â€‹± â€‹7.9 â€‹min (median, 21 â€‹min) for main OR specimens, and 26.4 â€‹± â€‹7.1 â€‹min (median, 25 â€‹min) for ASC specimens. Incision to close time for parathyroidectomies showed decreases in mean, median, and standard deviation following testing change. CONCLUSIONS: Surgery time for parathyroidectomies may remain consistent or decrease if intraoperative PTH testing is moved from a near point of care to a central laboratory.

The relationship between contralateral prophylactic mastectomy and breast reconstruction, complications, breast-related procedures, and costs: A population-based study of health insurance data.

BACKGROUND: Increasingly, women are undergoing contralateral prophylactic mastectomy for the treatment of unilateral breast cancer. The relationship between contralateral prophylactic mastectomy and breast reconstruction, postsurgical complications, additional breast-related procedures, and cost has not received the attention it deserves. METHODS: Data from the New York comprehensive, all-age, all-payer, Statewide Planning and Research Cooperative System were queried to identify patients undergoing unilateral mastectomy or contralateral prophylactic mastectomy from 2008 to 2010. We identified the complications and breast-related procedures within a 2-y follow-up period. Costs of the index operation and subsequent follow-up were estimated. Univariate and multivariate analyses were conducted. RESULTS: Of 12,959 women identified, 10.7% underwent contralateral prophylactic mastectomy. On univariate analysis, contralateral prophylactic mastectomy was positively associated with breast reconstruction, complications, and additional breast-related procedures. Rates of complications were greater for women who had contralateral prophylactic mastectomy (29.5% vs 20.8% for unilateral mastectomy group; P < .001), but not after stratifying by breast reconstruction. Additional breast-related procedures were more common in the contralateral prophylactic mastectomy group than in the unilateral mastectomy group, but only for those who underwent breast reconstruction (82.8% vs 72.1%; P < .001). Unadjusted costs were greater for women with contralateral prophylactic mastectomy than with unilateral mastectomy but did not differ between the groups after adjusting for breast reconstruction and additional breast-related procedures. CONCLUSION: Women who elected contralateral prophylactic mastectomy in this population-based study were more likely to have both breast reconstruction and additional breast-related procedures than women with unilateral mastectomy. The greater rates of complications and costs associated with contralateral prophylactic mastectomy were explained by breast reconstruction and additional breast-related procedures. Surgeons should counsel patients regarding the increased cost and likelihood of undergoing additional, non-complication-related procedures after contralateral prophylactic mastectomy with breast reconstruction.

Cancer cell-intrinsic function of CD177 in attenuating ß-catenin signaling.

Aiming to identify immune molecules with a novel function in cancer pathogenesis, we found the cluster of differentiation 177 (CD177), a known neutrophil antigen, to be positively correlated with relapse-free, metastasis-free, or overall survival in breast cancer. In addition, CD177 expression is correlated with good prognosis in several other solid cancers including prostate, cervical, and lung. Focusing on breast cancer, we found that CD177 is expressed in normal breast epithelial cells and is significantly reduced in invasive cancers. Loss of CD177 leads to hyperproliferative mammary epithelium and contributes to breast cancer pathogenesis. Mechanistically, we found that CD177-deficiency is associated with an increase in ß-catenin signaling. Here we identified CD177 as a novel regulator of mammary epithelial proliferation and breast cancer pathogenesis likely via the modulation of Wnt/ß-catenin signaling pathway, a key signaling pathway involved in multiple cancer types.

Rate of BRCA mutation in patients tested under NCCN genetic testing criteria.

BACKGROUND: BRCA genetic testing is recommended by the National Comprehensive Cancer Network (NCCN) in breast cancer patients who meet specific criteria. Limited data are available on the likelihood of detecting a mutation when these guidelines are followed. METHODS: A retrospective chart review examined patients with breast cancer who underwent BRCA testing based on NCCN guidelines. RESULTS: Twelve (6.0%) of the 199 patients had a deleterious BRCA mutation. Family history of BRCA mutations (50%, p = 0.019), age ≤45 at diagnosis (9.7%, p = 0.034) and meeting ≥3 NCCN criteria (13.3%, p = 0.03) yielded the highest rates of BRCA mutation. Having a family history of BRCA mutation and age ≤45 were associated with increased rate of BRCA mutation on multivariate analysis (OR 14.3, CI 1.2-166.3; OR 11.6, CI 1.2-108.6). CONCLUSION: Select NCCN criteria are associated with higher rates of BRCA mutations. Waiting for genetic testing results to guide surgical management may be warranted in this subset of patients.

Discordant findings on preoperative imaging for primary hyperparathyroidism and thyroid disease: Choosing the path to follow.

BACKGROUND: Preoperative localization of abnormal parathyroid glands in primary hyperparathyroidism is often obtained by sestamibi, and ultrasonography. We aimed to identify which modality is most accurate when laterality of abnormal glands on preoperative imaging is discordant. METHODS: A single institution retrospective review identified 112 consecutive patients with primary hyperparathyroidism who underwent successful parathyroidectomy and sestamibi with pertechnetate. RESULTS: Sestamibi with pertechnetate had a sensitivity of 72% and positive predictive value of 90%; ultrasonography had sensitivity of 50% and positive predictive value 80%. Patients with thyroiditis had lesser sensitivity and positive predictive value on sestamibi with pertechnetate (53% and 77%, respectively), in contrast to ultrasonography (54%, 88%, respectively). The sensitivity and positive predictive value of sestamibi with pertechnetate and ultrasonography did not differ in patients with thyroid nodules. Seventeen patients (15%) had discordant laterality on preoperative imaging. In discordant cases, sestamibi with pertechnetate was correct in 53% overall but in only 17% of those with thyroiditis (P = .01), whereas ultrasonography was correct in 26% overall but in 50% of those with thyroiditis (P = .01). CONCLUSION: Thyroiditis decreased the sensitivity and positive predictive value of sestamibi with pertechnetate in primary hyperparathyroidism. In patients with discordant laterality on preoperative imaging, sestamibi with pertechnetate is the more accurate choice to guide operative planning, although ultrasonography may be a better guide in those with thyroiditis.