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Background There is a growing body of evidence to support tears as a non-traditional biological fluid in clinical laboratory testing. In addition to the simplicity of tear fluid processing, the ability to access key cancer biomarkers in high concentrations quickly and inexpensively is significantly enhanced. Tear fluid is a dynamic environment rich in both proteomic and genomic information, making it an ideal medium for exploring the potential for biological testing modalities. Methods All protocols involving human subjects were reviewed and approved by the University of Arkansas IRB committee (13-11-289) prior to sample collection. Study enrollment was open to women ages 18 and over from October 30, 2017-June 19, 2019 at The Breast Center, Fayetteville, AR and Bentonville, AR. Convenience sampling was used and samples were age/sex matched, with enrollment open to individuals at any point of the breast health continuum of care. Tear samples were collected using the Schirmer strip method from 847 women. Concentration of selected tear proteins were evaluated using standard sandwich ELISA techniques and the resulting data, combined with demographic and clinical covariates, was analyzed using logistic regression analysis to build a model for classification of samples. Results Logistic regression analysis produced three models, which were then evaluated on cases and controls at two diagnostic thresholds and resulted in sensitivity ranging from 52 to 90% and specificity from 31 to 79%. Sensitivity and specificity variation is dependent on the model being evaluated as well as the selected diagnostic threshold providing avenues for assay optimization. Conclusions and relevance The work presented here builds on previous studies focused on biomarker identification in tear samples. Here we show successful early classification of samples using two proteins and minimal clinical covariates.

Background In 2017, the American Society of Breast Surgeons (ASBrS) published expert panel recommendations for patients at risk for breast cancer-related lymphedema (BCRL) and those affected by BCRL. This study sought to determine BCRL practice patterns. Methods A survey was sent to 2975 ASBrS members. Questions evaluated members' clinical practice type, practice duration, and familiarity with BCRL recommendations. Descriptive statistics, the chi-square test, and Fisher's exact test were used. Results Of the ASBrS members surveyed, 390 (13.1%) responded. Most of the breast surgeons (58.5%, 228/390) indicated unfamiliarity with recommendations. Nearly all respondents (98.7%, 385/390) educate at-risk patients. Most (60.2%, 234/389) instruct patients to avoid venipuncture, injection or blood pressure measurements in the at-risk arm, and 35.6% (138/388) recommend prophylactic compression sleeve use during air travel. Nearly all (97.7%, 380/389) encourage those at-risk to exercise, including resistance exercise (86.2%, 331/384). Most do not perform axillary reverse mapping (ARM) (67.9%, 264/389) or a lymphatic preventive healing approach (LYMPHA) (84.9%, 331/390). Most (76.1%, 296/389) screen at-risk patients for BCRL. The most frequently used screening tools include self-reported symptoms (81%, 255/315), circumferential tape measure (54%, 170/315) and bioimpedance spectroscopy (27.3%, 86/315). After a BCRL diagnosis, most (90%, 351/390) refer management to a lymphedema-certified physical therapist. For affected patients, nearly all encourage exercise (98.7%, 384/389). Many (49%, 191/390) refer affected patients for consideration of lymphovenous bypass or lymph node transfer. Conclusion Most respondents were unfamiliar with the ASBrS expert panel recommendations for patients at risk for BCRL and those affected by BCRL. Opportunities exist to increase awareness of best practices and to acquire ARM and LYMPHA technical expertise.

The number of involved lymph nodes negatively affects prognosis in breast cancer patients. Nevertheless, current staging and treatment recommendations do not distinguish between patients with single versus multiple lymphatic micrometastases. In this study, we aim to better characterize these patients. The National Cancer Database was retrospectively queried to identify 486,800 women with stage I–III, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER+/PR+/HER2−) breast cancer and nodal status of N0, N1mi with 1 (Nmic1) or more (Nmic > 1) involved nodes, and N1 with 1 involved node (N1.1), from 2010 to 2016. Patients with different nodal statuses were compared regarding treatment characteristics, survival, and benefit from chemotherapy by their 21-gene recurrence score (RS). Of the 23,072 N1mi patients, 88.3% were Nmic1 and 11.7% were Nmic > 1. Nmic > 1 patients were younger, had larger and higher-grade tumors, with more lymphovascular invasion, and were more commonly treated by axillary dissection, radiation, and chemotherapy than Nmic1 patients. In that, they were comparable with N1.1 patients. Five-year survival of Nmic > 1 patients (88.1%) was worse than Nmic1 patients (90.1%; p = 0.02), but similar to N1.1 patients (87.9%). Nmic1, Nmic > 1, and N1.1 patients with RS 11–25 exhibited a 25, Nmic > 1 patients showed a 3.5% benefit, similar to Nmic1 (4.8%) and lower than N1.1 (10.9%) patients. Nmic > 1 breast cancer patients have worse prognoses than Nmic1 patients, similar to N1.1 patients. Our data suggest those patients with RS 11–25 have minimal benefit from chemotherapy. These findings should be taken into account when discussing prognosis and considering chemotherapy in patients with lymphatic micrometastases.

BACKGROUND: The use of robotics in colorectal surgery has been steadily increasing, however reported longer operative times and increased cost has limited its widespread adoption. We investigated the cost of elective colorectal surgery based on type of anatomic resection and the impact of a standardized protocol for robotic colectomies. METHODS: A retrospective review was conducted of 279 elective colectomies at a single institution between 2013–2017. Clinical outcomes and detailed cost data were compared based on open, laparoscopic, or robotic surgical approach and stratified by anatomic resection. RESULTS: Robotic, laparoscopic and open colectomy rates were 35, 34 and 31%, respectively. While total costs were similar in robotic and laparoscopic surgery, anatomic resection stratification showed that low anterior resection (LAR) was significantly cheaper ($14,093 vs $17,314). When a standardized surgical protocol was implemented for robotic colectomies, significant reductions in operative times, length of stay, total cost, and operative cost were observed. CONCLUSIONS: Robotic surgery may be most cost effective for elective LAR compared to laparoscopic or open approaches. A standardized surgical protocol for robotic surgery may help reduce costs by reducing operative times, operating rooms expenditure, and lengths of stay.

The 21-gene recurrence score assay (RS) has not been prospectively validated to predict adjuvant chemotherapy benefit in hormone receptor-positive (HR+), HER2-negative (HER2−), node-positive breast cancer patients. Nevertheless, de-escalation based on RS has been demonstrated and partially advocated by retrospective data. The purpose of this study was to identify subgroups of node-positive patients with low to intermediate RS who still benefit from adjuvant chemotherapy. The National Cancer Database was used to identify 28,591 women with stage I–III, T1–T3, N1, HR+, HER2− breast cancer and a RS ≤ 25 between 2010 and 2016. Univariate and multivariate analyses were used to identify variables correlating with chemotherapy use and 5-year survival. Subgroup analysis was performed to discern patients in whom the use of adjuvant chemotherapy correlated with better survival. A 35% decline in chemotherapy use was observed from 2010 to 2016. Patients with younger age, higher RS, larger tumors and more positive lymph nodes, and those treated by mastectomy, axillary lymph node dissection and radiation, were more likely to receive chemotherapy. Chemotherapy use was associated with an improved 5-year survival (HR = 1.63, 95% CI 1.28–2.07). Upon subgroup analysis, this association was lost in patients > 70 years and those with a RS ≤ 11, while patients ≤ 70 with a RS of 12–25 treated with chemotherapy had an absolute 5-year survival advantage of 3.0% (HR = 1.91, 95% CI 1.42–2.57). Clinicians should be cautious when considering omission of adjuvant chemotherapy in patients ≤ 70 years, with HR+, HER2−, N1 tumors and a RS 12–25, at least until the results of the anticipated RxPONDER trial become available.

Localization of nonpalpable breast lesions for breast-conserving surgery (BCS) remains highly variable and includes needle/wire localization (NL), radioactive seed localization, radar localization, and hematoma-directed ultrasound-guided (HUG) lumpectomy. The superiority of HUG lumpectomy over NL has been demonstrated repeatedly in terms of safety, accuracy, low positive margin rates, cosmesis, and patient satisfaction. In this study, we evaluate the cost effectiveness of HUG lumpectomy over NL for nonpalpable breast lesions. We performed a retrospective review of 569 patients who underwent lumpectomy at the University of Arkansas for Medical Sciences from May 2014 through December 2017. Lumpectomies were stratified by localization technique, i.e. NL versus HUG. A cost-savings estimate was determined for the HUG localization technique, and a total amount of dollars saved over the study period was calculated. Overall, 569 lumpectomies were performed: 501 (88.0%) via HUG and 68 (12.0%) via NL. Intraoperative ultrasound was used in 566 operations (99.5%). Of the lumpectomies performed by HUG, 190 lesions (33.4%) were visible only on mammogram or breast magnetic resonance imaging prior to diagnostic core needle biopsy (CNB). Cost estimates comparing HUG with NL demonstrated a cost savings of $497.00 per procedure, the cost of preoperative needle localization by a radiologist, and a total of $94,430.00 for the study period. In utilizing HUG lumpectomy, the initial CNB serves as the diagnostic and localization procedure, thus saving time and a painful second procedure on the day of operation. HUG lumpectomy is safe, accurate, reduces healthcare costs, and results in a better patient experience for the surgical removal of nonpalpable breast lesions.

Medullary breast cancer (MBC) is a rare tumor associated with a better prognosis compared with other breast cancers. The role of adjuvant chemotherapy has not been extensively studied.Female patients with invasive MBC reported to the National Cancer Data Base from 2004 to 2012 were analyzed. Overall survival (OS) and treatment were studied using the Kaplan-Meier method and the Cox proportional hazard model. Patients who had node-negative (N0), non-metastatic (M0) tumors 10 to 50 mm in size (T1cN0M0 and T2N0M0) treated with and without chemotherapy were analyzed using propensity score matching.Of 3739 patients with MBC, 2642 (71%) had T1b-T2N0M0 disease treated with and without chemotherapy. Multivariable analysis showed that for all MBC patients, the significant predictors of OS were age older than 65 years, one or more comorbidities, tumor larger than 2 cm, positive nodes, distant metastasis, and treatment with chemotherapy or radiation therapy. Patients with T1cN0M0 and T2N0M0 had improved OS if they received chemotherapy (p 0.0005). Patients with T1bN0M0 who received chemotherapy did not show better OS than those who did not. Patients with T1c-T2N0M0 were then matched by propensity score based on age, presence of comorbidities, tumor size, and treatment methods used. After matching, the group receiving chemotherapy showed an improved OS (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.26-0.62; p 0.0005) compared to the group that did not receive chemotherapy.For patients with T1c-T2N0M0 MBC, chemotherapy significantly improves OS.

Performing a sentinel lymph node biopsy (SLNB) is the standard of care for axillary nodal staging in patients with invasive breast cancer and clinically negative nodes. The procedure provides valuable staging information with few complications when performed by experienced surgeons. However, variation in proficiency exists for this procedure, and a great amount of experience is required to master the technique, especially when faced with challenging cases. The purpose of this paper was to provide a troubleshooting guide for commonly encountered technical difficulties in SLNB, and offer potential solutions so that surgeons can improve their own technical performance from the collective knowledge of experienced specialists in the field. Information was obtained from a convenience sample of six experienced breast cancer specialists, each actively involved in training surgeons and residents/fellows in SLNB. Each surgeon responded to a structured interview in order to provide salient points of the SLNB procedure. Four of the key opinion surgical specialists provided their perspective using technetium-99 m sulfur colloid, and two shared their experience using blue dye only. Distinct categories of commonly encountered problem scenarios were presented and agreed upon by the panel of surgeons. The responses to each of these scenarios were collected and organized into a troubleshooting guide. We present a compilation of ‘tips’ organized as a troubleshooting guide to be used to guide surgeons of varying levels of experience when encountering technical difficulties with SLNB.

The recently published SSO-ASTRO consensus guideline on margins concluded "no ink on tumor" is the standard for an adequate margin. This study was conducted to determine how this guideline is aligned with current clinical practice.A survey was sent to 3057 members of the American Society of Breast Surgeons. Questions assessed respondents' clinical practice type and duration, familiarity with the guideline, and preferences for margin re-excision.Of those surveyed, 777 (25%) responded. Most (92%) indicated familiarity with the guideline. Of these respondents, the majority (n = 678, or 94.7%) would re-excise all or most of the time when tumor extended to the inked margin. Very few (n = 9, or 1.3%) would re-excise all or most of the time when tumor was within 2 mm of the margin. Over 12 % (n = 90) would re-excise all or most of the time for a triple-negative tumor within 1 mm of the margin, whereas 353 (49.6%) would re-excise all or most of the time when imaging and pathology were discordant, and tumor was within 1 mm of multiple margins. Finally, 330 (45.8%) would re-excise all or most of the time when multiple foci of ductal carcinoma in situ extended to within 1 mm of multiple inked margins.Surgeons are in agreement to re-excise margins when tumor touches ink and generally not to perform re-excisions when tumor is close to (but not touching) the inked margin. For more complex scenarios, surgeons are utilizing their individual clinical judgment to determine the need for re-excision.

The evidence available for risk reduction of lymphedema after breast cancer treatment is sparse and inconsistent. It is limited by confounding factors such as axillary disease burden, number of lymph nodes harvested, and radiation treatment. However, there are several strategies for prevention and risk reduction prior to the onset of lymphedema. Techniques such as sentinel lymph node biopsy, axillary reverse mapping, lymphatic anastomosis, and lymphovenular anastomosis are aimed at preventing or minimizing the disruption of lymphatic flow from the upper extremity. Few surgical procedures, such as the historical Charles procedure, as well as newer techniques including distal lymphaticovenular anastomosis, lymph node transfer, suction-assisted protein lipectomy, and low-level laser therapy exist. Nonsurgical treatments include complete decongestive therapy, pneumatic compression, Kinesio tape, and exercise. These have varying degrees of effectiveness but have limitations in patient compliance or availability of certified therapists.

Glenda G. Callender, MD, Brian J. Kaplan, MD, Richard L. White, MD, David R. Brenin, MD, Anees B. Chagpar, MD, MSc, MA, MPH, MBA, Kimberly M. Dalal, MD, Marissa Howard-McNatt, MD, James Howe, MD, Joseph Kim, MD, Scott H. Kurtzman, MD, John C. Mansour, MD, Elizabeth A. Mittendorf, MD, PhD, John H. Stewart IV, MD, Larissa K. F. Temple, MD, Patti Stella, BA, CCMEP, Charmaine Cummings, PhD, RN, CCMEP, Sandra L. Wong, MD, MS, and V. Suzanne Klimberg, MD

Advanced locoregional therapies continue to advance the treatment of breast cancer. These techniques are geared towards optimizing oncologic and aesthetic outcome as well as decreasing and treating morbidity. We present a selection of specialized locoregional therapies dedicated to the optimization of breast cancer treatment.Locoregional therapies for breast cancer are presented to address breast conservation techniques, lipofilling techniques, reconstruction techniques for nipple-sparing mastectomy, re-irradiating the breast, axillary reverse mapping, and vascularized lymph node transfer.We present a synopsis of identified breast locoregional therapies targeted to address optimal oncologic and aesthetic outcome as well as decrease and treat morbidity.

In a prior Presidential Address I talked of how important it was to have an attitude of gratitude. I still maintain this and am grateful for all the opportunity that life and the American Society of Breast Surgeons have afforded me. Mentors. Mentors come in many forms and sometimes are lifelong and span continents. In terms of my initial surgery and research training, J.J. Marshal, PhD, Edward M. Copeland, MD, Kirby I. Bland, MD, Charles Badgwell, MD, Farhat Moazam, MBBS, Tim Flynn, MD, and Wiley ‘‘Chip’’ Souba, ScD, MD have contributed greatly to my training not only in surgery but in the laboratory in which I spent four of my years. During that training my fellow residents were a constant stimulus to know more, do more, create more, and write more. Beyond those initial years others have afforded more opportunities and advised me on organizational paths to achieving my goals including but not limited to Ted Copeland, MD and Kirby Bland, MD, Charles Balch, MD, Dr. Fabrizio Michelassi, MD, Shirley Graves, PhD, Carlos Pelligrini, MD, David P. Winchester, MD, Jack Hollenbeck, MD, Mel Silverstein, MD, Art Lerner, MD, and Vic Zannis, MD. Legislative. I have had the good fortune to be involved in writing six different laws to upgrade the care of breast patients in Arkansas and am grateful for the legislative savvy and work of Josetta Wilkins, PhD and Cherry Duckett. Surgical Colleagues. I am grateful to all the Surgery Department at University of Arkansas for Medical Sciences and my Division, Kent Westbrook, MD, Ronda HenryTillman, Cristiano Boneti, MD, Daniela Ochoa, MD, Anne Mancino, MD, Maureen McCarthy, RN OCN, and Laura Adkins, MPh, Fellows in Diseases of the Breast, and all the nurses and scrubs in the operating room as well as all the members of our multidisciplinary team. Research Colleagues. Thanks to Soheila Korourian, MD, Issam Makhoul, MD, Larry Suva, PhD, ‘‘Tears for Life,’’ Steve Harms, MD, YiHong Kaufmann, PhD and Valentina Todorova, PhD, Laura Adkins, MS and Maureen McCarthy, RN, OCN, Susan Kadlubar, PhD and ‘‘Spit for the Cure,’’ Sharp Malak, MD, MPH, Fellows including long-time research partner Isabel Rubio, MD, and contributors and partners in the ABLATE multicenter trial and ARM. More importantly thanks to the more than 25,000 pioneers (patients) who gave of themselves for our breast cancer research at the Winthrop P. Rockefeller Institute. Education. My partners in education have been my Breast Cancer Challenge Organizing Committee from Kansas, Oklahoma, Missouri, and Arkansas including our Program Chair this year, Julie Margenthaler, MD, and Committee Chairs and Members who went through a GREAT planning process this year. Thanks to Jane and all her posse for her inordinate leadership as our executive director and workforce. Family. Finally, thanks to my ultimate supporters and facilitators Sam, Spencer, Sade, and to those who have adopted me into their family. There are so many more to thank, so forgive me if I did not include your name but know I appreciate all your efforts on behalf of myself and the mission of the American Society of Breast Surgeons. The title of my address is ‘‘Treatment by Chance.’’ I have taken the title of this talk from an article my former Chair of Surgery at Arkansas Kent Westbrook, MD, who wrote more than 30 years ago about the disparity of care at a time when the debate of the safety of mastectomy versus breast conservation was still raging. In speaking with then President of the American College of Surgeons, Dr. Patti Neumann, she reiterated that what is happening today is no Society of Surgical Oncology 2013

Adenoid cystic carcinoma (ACC) is a rare subtype of breast malignancy. Patients with ACC and infiltrating ductal carcinoma (IDC) reported to the National Cancer Data Base from 1998 to 2008 were reviewed for patient age, ethnicity, tumor size, nodal status, American Joint Committee on Cancer TNM Stage, tumor grade, initial treatment, hormone receptor status (for patients from 2004 to 2008), and survival (for patients from 1998 to 2003). A total of 933 patients with ACC and 729,938 with IDC were identified. No differences were found for incidence by race/ethnicity (p = 0.97). The group with ACC was older (median 60 vs. 58 years), had larger tumors (median 18 vs. 16 mm), had more grade 1 tumors (46 vs. 18 %), was less likely to undergo axillary lymph node evaluation (75.9 vs. 96.3 %), had fewer node-positive patients (5.1 vs. 35.5 %), had fewer estrogen receptor–positive tumors (15.4 vs. 75.6 %), had fewer progesterone receptor–positive tumors (13.3 vs. 65.2 %), and underwent breast-conserving surgery more often (69.8 vs. 59.8 %). Chemotherapy was provided less often for ACC (11.3 vs. 46.4 %), as was hormone therapy (9.1 vs. 42.3 %). All of these differences were statistically significant (p

Triple-negative breast cancer (TNBC) has a poorer prognosis; the factors that contribute to this remain unclear. We hypothesized that TNBC is associated with ABO blood type/Rh factors that account for differences in survival.We identified 468 patients with stage I-III TNBC [estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2 nonamplified]. Patient/tumor characteristics, treatments, and outcomes were obtained. Data were examined for associations with specific ABO blood type/Rh factors. Descriptive statistics and χ (2) analysis were utilized for data summary and comparisons.Of 468 TNBC patients, 283 had known ABO blood type [122 (43 %) O, 108 (38 %) A, 39 (14 %) B, and 14 (5 %) AB] and Rh factor [253 (89 %) positive and 30 (11 %) negative]. Mean patient age was 53.7 ± 12.5 years, and median follow-up was 30.2 ± 20.5 months. The incidence of each ABO blood type/Rh factor in our TNBC cohort was not different from the general population or a cohort of ER-positive breast cancers (P0.05). Compared with patients with blood type O, there was no difference in breast cancer-specific mortality for type A [hazard ratio (HR) 0.906; 95 % confidence interval (CI) 0.554-1.481], type B (HR 1.534; 95 % CI 0.792-2.972), or type AB (HR 0.488; 95 % CI 0.113-2.106). Compared with women with negative Rh, there was no difference in breast cancer-specific mortality for women with positive Rh (HR 1.161; 95 % CI 0.568-2.374).TNBC was not associated with a specific ABO blood type or Rh factor. Our results failed to demonstrate an association between ABO blood type/Rh factor and breast cancer mortality in patients with TNBC.

To examine gender-specific differences in breast cancer utilizing the National Cancer Data Base (NCDB).Breast cancer patients entered in the NCDB from 1998 through 2007 were compared by gender for demographics, tumor characteristics, treatment, and outcomes.A total of 13,457 men were compared to 1,439,866 women. Men were older, more often African American, less often Hispanic, had larger tumors, less often had low-grade disease, less often had stage 0 or I disease, and were more likely to have metastases to lymph nodes and/or distantly. Cancers in men were less likely lobular and more likely estrogen receptor and/or progesterone receptor positive. Men were more likely to have total mastectomy and less likely to receive radiotherapy. There was no difference in chemotherapy and little difference in hormone therapy rates. Differences in overall survival (OS) were highly significant (p0.0001): 83 % 5-year OS for women with breast cancer (median survival 129 months) versus 74 % for men (median survival 101 months). Women had better 5-year OS (p0.0001) for stage 0 (94 vs. 90 %), stage I (90 vs. 87 %), and stage II (82 vs. 74 %) breast cancer. There were no differences in 5-year OS for stage III (56.9 vs. 56.5 %, p = 0.99) or stage IV (19 vs. 16 %, p = 0.20) disease.At first glance, this large study demonstrated numerous gender-specific differences. However, after accounting for differences in presentation, absence of data on disease-specific survival, and inherent deficiencies in reporting cancer registry data, breast cancer in men and women appears more alike than different.

The purpose of this study was to determine the feasibility and optimal timing of quality of life assessment for patients undergoing palliative surgical evaluation.Patients with an advanced malignancy undergoing consultation for palliative surgical intervention were prospectively enrolled from November 2009 to January 2011. Follow-up quality of life assessment was performed using validated instruments at 1 and 3 months post-enrollment. Univariate analysis of variables was performed to identify clinicopathologic variables associated with questionnaire completion.Of 77 patients enrolled, the most common clinical presentations included bowel obstruction (32 %), abdominal pain (21 %), wound complications (18 %), and gastrointestinal bleeding (11 %). Of the 77 patients, 34 (44 %) were treated with nonoperative/nonprocedural care, 9 (12 %) with endoscopic or interventional radiologic procedures, and 34 (44 %) with surgery. Follow-up questionnaires were obtained at 1 month and 3 months in 48 % and 15 %, respectively. A total of 31 patients (40 %) died prior to study completion. On univariate analysis, death was the only factor associated with questionnaire response. All other demographic, clinical, and treatment variables were not associated with response to questionnaires. There were no significant differences in baseline or follow-up quality of life scores between patients treated with surgical intervention or nonoperative management.Death during the study period was a significant factor in limiting adequate follow-up assessment. Future studies attempting to obtain follow-up data on patients evaluated for palliative surgical intervention may require larger patient numbers to account for frequent early death in this population and anticipate the need to account for the high rate of missing data in statistical analysis.

We previously introduced the concept of margin index as a method for prediction of residual disease after attempted breast-conserving therapy (BCT). We sought to apply the margin index to patients with ductal carcinoma in situ (DCIS) to determine its reliability in predicting residual disease. We identified all patients with DCIS who were treated with BCT from 2004 to 2010. Margin index was calculated as follows: margin index = closest margin (mm)/tumor size (mm) × 100. A receiver operating curve was created using the derived margin index and the presence or absence of residual disease in the re-excision specimen. Sensitivity and specificity were calculated at various margin indices to identify the optimum margin index. Of 380 patients undergoing attempted BCT, 109 (29%) underwent re-excision. Of 109 patients undergoing re-excision, 46 (42%) had positive margins and were excluded from the study, 15 (14%) were excluded due to inability to determine the size of DCIS on pathology reports, and 48 (44%) met study criteria and were included in the analysis. Of 48 patients undergoing re-excision, 19 (40%) had residual disease. The receiver operating curve c index was 0.65. However, there was no optimum margin index that reliably predicted the presence or absence of residual disease. Margin index is not a reliable method for prediction of residual disease after attempted BCT with close margins in patients with DCIS only. This may be a reflection of the complexities in accurately determining DCIS size and margin status in pathologic specimens.

Percutaneous ablation of breast cancer has shown promise as a treatment alternative to open lumpectomy. We hypothesized that percutaneous removal of breast cancer followed by percutaneous ablation to sterilize and widen the margins would not only provide fresh naive tissue for tumor marker and research investigation, but also better achieve negative margins after ablation. Patients diagnosed by percutaneous biopsy (ultrasound or stereotactic-guided) with breast cancer ≤1.5 cm, >1 cm from the skin, and ≤1 cm residual disease and no multicentric disease by magnetic resonance imaging were accrued to this institutional review board–approved study. Patients were randomized to laser versus radiofrequency ablation. The ultrasound-guided ablation was performed in the operating room and followed by immediate excision, whole-mount pathology with proliferating cell nuclear antigen staining, and reconstruction. Twenty-one patients were enrolled onto the study. Fifteen patients received radiofrequency ablation, and all showed 100% ablation and negative margins. Magnetic resonance imaging was helpful in excluding multicentric disease but less so in predicting presence or absence of residual disease. Seven of these patients showed no residual tumor and eight showed residual dead tumor (0.5 ± 0.7 cm, range 0.1–2.5 cm) at the biopsy site with clear margins. The laser arm (3 patients) pathology demonstrated unpredictability of the ablation zone and residual live tumor. This pilot study demonstrates the feasibility of a novel approach to minimally invasive therapy: percutaneous excision and effective cytoreduction, followed by radiofrequency ablation of margins for the treatment of breast cancer. Laser treatment requires further improvement.

Pain is one of the most commonly reported breast complaints. Referred pain from inflammation of the shoulder bursa is often overlooked as a cause of breast pain. The objective of this study is to evaluate the role of shoulder bursitis as a cause of breast/chest pain. An IRB-approved retrospective review from July 2005 to September 2009 identified 461 patients presenting with breast/chest pain. Cases identified with a trigger point in the medial aspect of the ipsilateral scapula were treated with a bursitis injection at the point of maximum tenderness. The bursitis injection contains a mixture of local anesthetic and corticosteroid. Presenting complaint, clinical response and associated factors were recorded and treated with descriptive statistics. Average age of the study group was 53.4 ± 12.7 years, and average BMI was 30.4 ± 7.4. One hundred and three patients were diagnosed with shoulder bursitis as the cause of breast pain and received the bursitis injection. Most cases (81/103 or 78.6%) presented with the breast/chest as the site of most significant discomfort, where 8.7% (9/103) had the most severe pain at the shoulder, 3.9% (4/103) at the axilla and 3.9% (4/103) at the medial scapular border. Of the treated patients, 83.5% (86/103) had complete relief of the pain, 12.6% (13/103) had improvement of symptoms with some degree of residual pain, and only 3.9%(4/103) did not respond at all to the treatment. The most commonly associated factor to the diagnosis of bursitis was the history of a previous mastectomy, present in 27.2% (28/103) of the cases. Shoulder bursitis represents a significant cause of breast/chest pain (22.3% or 103/461) and can be successfully treated with a local injection at site of maximum tenderness in the medial scapular border.

Pain, patient inconvenience, vasovagal symptoms, scheduling problems, wire malposition, and a positive margin rate of 40-75% are problems commonly associated with needle localized biopsy (NLBB). Despite these issues, NLBB is still the primary means of identifying nonpalpable lesions in the breast. We hypothesized that the hematoma-directed ultrasound-guided (HUG) procedure for intraoperative localization of nonpalpable lesions would allow for lumpectomy without the downfalls of needle localization and decrease the high positive-margin rate with NLBB.This is a retrospective study from January 2000 to October 2009. Electronic chart review identified lumpectomy procedures performed in the clinic and operating room. These patients underwent preoperative core-biopsy diagnosis by ultrasound (US) or stereotactic means. When excision was necessary needle localization or HUG was planned. A multifrequency linear array transducer was used intraoperatively for the HUG procedures, and a block of tissue surrounding the hematoma was removed.Localization procedures were performed in 455 patients: 126 (28%) via needle localization and 329 (72%) via HUG. The previous core-biopsy site in 100% of patients was successfully excised using HUG: 152 of 329 (46%) were benign and 177 of 329 (54%) were malignant. Margins were positive in 42 of these 177 cases (24%). was successful in 100% of patients: 88 of 126 (70%) were benign and NLBB 38 of 126 (30%) were malignant; margins were positive in 18 of these 38 (47%). Margin positivity was significantly higher for NLBB than HUG (P = 0.045, Fisher exact).This 10-year experience, representing the largest to date, suggests that HUG is more accurate in localizing nonpalpable lesions than NLBB. Compared with the additional painful procedure of NLBB, HUG is more time and cost-efficient. Preoperative needle core biopsy is not only the minimally invasive diagnostic procedure of choice, but also becomes the localization procedure when excisional biopsy is necessary.

The Annals of Surgical Oncology is in its 17 year of publication. As the journal has matured, it has become the most cited surgical oncology journal published and has been adopted as the venue for communicating new knowledge by surgeons all over the world. Manuscript submissions have increased by 65% between 2007 and 2009, the majority (70%) of which now originate from outside the United States (Fig. 1). The Annals is also the primary resource for surgeons practicing in the United States, both in academic and community practice settings, because it is read by all members of the Society of Surgical Oncology (the majority of whom are in an academic practice) and the American Society of Breast Surgeons (the majority of whom are in a community-based practice). The Annals has also become an official journal with surgical and oncology societies in Europe, Latin America, and Africa. Thus, the readership and authorship constituency of the Annals of Surgical Oncology now reaches across the globe—both in print and electronically— for surgeons treating patients with cancer. The scientific value of the journal is benchmarked with the Science Citation index. We are pleased to report that the journal’s impact factor has increased almost 2 points to 4.13, and the journal is now ranked 6th out of 166 surgery journals (Fig. 2, Table 1). This increase in impact is significant because it occurred despite an increased number of published pages from 2006 to 2007 (1753 vs 3637 printed pages), a variable that can push a journal’s measured impact downward by expanding the denominator. Since the number of published pages remained stable over the past 2 years, we are hopeful that the impact factor will continue to increase. During 2009, articles published in the Annals of Surgical Oncology in 2007 and 2008 were cited in 3527 articles published in the literature. Given the growth of highquality papers published in the journal, the impressive volume of citations in recently published articles reflects the scholastic influence of Annals articles on the field of surgical oncology, both in the clinical and the research spheres. The editorial leadership of the journal is also broadened to reflect the leadership of cancer surgeons not only in the United States, but also around the globe. The 2010–2011 Editorial Board roster, available online and in the front of this issue, displays the new and continuing Editorial Board members as well as two new subgroups—International Associate Editors and the Latin American Scientific Advisory Board. The addition of these international leaders to the journal reflects the increase visibility, usage, and citations of ASO worldwide. We are also pleased to formally welcome Suzanne Klimberg, MD, to her new role as Deputy Editor of the journal; in this position, Suzanne is leading the journal as it becomes positioned to be an explicit educational resource for Maintenance of Certification. Dr. Eric Whitacre and colleagues have successfully piloted the Mastery of Breast Surgery, which is a case log system focused on three outcome measures specific to breast. This log qualifies for MOC Part IV and recently has been ‘‘linked’’ to the ASO to aid in obtaining credit for Part II. The SSO has appointed a committee to develop other venues for the surgical oncologist that includes Drs. Clifford Ko, Jeff Gershenwald, Doug Tyler, and Suzanne Klimberg. They hope to pilot a similar model for the American College of Surgeon Case log in five cancer areas with content specialist in each area. Society of Surgical Oncology 2010

We hypothesized that the optimum margin after breast-conserving therapy (BCT) should depend on the original size of the tumor. We propose that “margin index”—a relationship of the margin obtained to the size of the tumor—is a better predictor of residual disease on reexcision than margin alone. We identified 475 consecutive patients with Stage I-II breast cancer, with or without ductal carcinoma in situ, who were treated with BCT from 1998–2008 who also underwent reexcision for close margins. Margin index was calculated as follows: margin index = closest margin (mm)/tumor size (mm) × 100. A receiver operating curve was created using the derived margin index and the presence or absence of residual disease in the reexcision specimen. Sensitivity and specificity were calculated at various margin indices to determine the optimum margin index. Of the 475 patients, 102 (21%) had residual disease in the reexcision specimen. The optimum margin index was >5; the risk of residual disease for a margin index >5 was only 3.2%. The sensitivity and specificity of a margin index cutoff of 5 was 85 and 73%, respectively. The overall c index for the receiver operating curve was 0.88. The margin index was the only factor predictive of residual disease in multivariate analysis. Margin index is a reliable method for the prediction of residual disease after attempted BCT with close margins. This simple calculation may be helpful for identifying patients who require reexcision before radiation therapy and those who may be able to forego additional surgical interventions.

Needle localization breast biopsy (NLBB) is presently the primary means of localizing non-palpable lesions. Disadvantages of NLBB include vasovagal episodes, patient discomfort, and miss rates. Because hematomas naturally fill the cavity after vacuum-assisted breast biopsies (VABB), we hypothesized that ultrasound (US) could be used to find and accurately excise the actual biopsy site of non-palpable breast lesions without a needle. This is a retrospective study from January 2000 to July 2005. Electronic chart review identified patients with non-palpable breast lesions detected by means of mammogram who then underwent lumpectomy via NLBB or the hematoma-directed ultrasound-guided technique (HUG). HUG involved localizing the hematoma with a 7.5-MHz US probe and using the “line of sight” technique straight down toward the chest wall. A block of tissue encompassing the hematoma was then excised. Localization procedures were performed in 186 patients—63 (34%) via needle localization and 123 (66%) via HUG. The previous VABB site in 100% of patients was successfully excised using HUG, 65 of 123 (53%) were benign and 58 of 123 (47%) were malignant; margins were positive in 13 of these 58 (22%). NLBB was successful in 100% of patients, 44 of 63 (70%) were benign and 19 of 63 (30%) were malignant; margins were positive in 14 of these 19 (73%). Margin positivity was significantly higher for NLBB than HUG (P = 0.0001, Fisher Exact). This study suggests that HUG is more accurate in localizing non-palpable lesions than NLBB. By eliminating the additional procedure needed for NLBB, HUG may also be more time- and cost efficient. HUG makes VABB not only a less invasive diagnostic procedure, but also a localization procedure.

Glutamine (GLN) is a non-essential amino acid that is present in nearly every biochemical pathway and is the major intraorgan nitrogen carrier. GLN via glutamate, is one of the precursors for the synthesis of glutathione (GSH), the major endogenous antioxidant in mammalian cells, which protects them from oxidative injury and cell death. Cancer cells have higher GSH levels than the surrounding normal cells, which attributes to a higher rate of cell proliferation and resistance to chemotherapy. Therefore, selective tumor depletion of GSH presents a promising strategy in cancer treatment. Experimental studies have associated decreased GSH levels with inhibition of proliferation and stimulation of apoptosis. Previous results of our laboratory have provided evidence that dietary GLN diminished tumor development in implantable as well as 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer and elevated GSH in the host tissues. In this study we examined the effects of GLN on GSH levels in DMBA-induced mammary tumors and correlated the results with protein and mRNA expression of apoptosis-related proteins Bcl-2, Bax and caspase-3 in tumor cells. The results have shown that GLN supplementation caused a significant decrease in the tumor GSH levels and the ratio GSH/oxidized GSH (GSSG), accompanied by up-regulation of Bax and caspase-3, and down-regulation of Bcl-2. These findings suggest that dietary GLN supplementation suppresses mammary carcinogenesis by activation of apoptosis in tumor cells and this probably is a result of GSH down-regulation.

The rates of contralateral prophylactic mastectomy (CPM) have markedly increased in the US over the past 2 decades. These trends have been observed in all patient age groups, cancer stages, races, and in all geographic regions of the US. In the most recently published analyses from the Surveillance Epidemiology and End Results database, the CPM rates were still increasing with no plateau. Most patients who undergo CPM do not have strong genetic or familial risk factors for developing contralateral breast cancer. Recent survey studies have demonstrated that breast cancer patients substantially overestimate the risk of contralateral breast cancer and have unrealistic outcomes from CPM. Moreover, in a survey study among active members of the American Society of Breast Surgeons (ASBrS), Yao et al. concluded that 39.2 % of respondents had a ‘low level of knowledge about CPM’. Given the gaps in knowledge among both patients and surgeons, the publication of the ASBrS consensus statement is timely. In 1993, the Society of Surgical Oncology (SSO) developed a position statement on the use of CPM, which was most recently edited and updated in March 2007. Since the last revision of this position statement, many important studies have been published evaluating the risks of contralateral breast cancer, outcomes after CPM, and patients’ perceptions and preferences. The ASBrS consensus statement appropriately incorporates most of this relevant recent research. In the strongest language to date, the consensus statement recommends that CPM should be ‘discouraged’ for patients with an average risk of contralateral breast cancer. This population of patients represents the vast majority of women who undergo CPM in the US. The statement further concludes that ‘CPM should be considered’ for selected groups at significant risk of contralateral breast cancer (including carriers of BRCA 1 or 2 deleterious mutations). Furthermore, ‘CPM can be considered’ for selected groups at lower risk of contralateral breast cancer (including other gene mutation carriers). Additionally, ‘CPM may be considered’ for non-oncologic reasons (including limiting contralateral breast surveillance). Finally, ‘CPM should be discouraged’ for patients with advanced primary-stage breast cancer and patients who are in overall poor health or at very high risk of associated complications. In recent years, there has been a rapid proliferation in the number and scope of published clinical practice guidelines and consensus statements. To address the substantial variation in the clinical guideline development processes, the Institute of Medicine (IOM) published eight standards in ‘Clinical Practice Guidelines We Can Trust’ in 2011. Although there are subtle differences between consensus statements and clinical practice guidelines, both should be transparent, multidisciplinary, evidence-based, and intended to provide guidance to clinicians and patients. The ASBrS CPM consensus statement adheres to some, but not all, of the IOM standards. For example, the IOM recommends that the clinical guideline development group be multidisciplinary, balanced, and include current/former Society of Surgical Oncology 2016

Breast tumor infiltrating lymphocytes (TIL) are enriched in tumor-specific cytotoxic T lymphocytes (CTL), and may represent a superior source of CTL compare to peripheral blood lymphocytes (PBL), for adoptive T cell immunotherapy of breast cancer. However, the immunocompetence of TIL and the possibility to consistently restore their tumor-specific lytic activity in vitro remains an open issue. In this study we evaluated the potential of tumor antigen-pulsed fully mature dendritic cell (DC) stimulation in restoring tumor-specific cytotoxicity in anergic TIL populations from advanced breast cancer patients. In addition we have compared tumor-specific T cell responses induced by tumor antigen-loaded DC stimulation of TIL to responses induced from PBL. Although TIL were consistently non-cytotoxic after isolation or culture in the presence of interleukin-2 (IL-2), in matched experiments from three consecutive patients, tumor-lysate-pulsed DC-stimulated CD8+ T cell derived from TIL were found to be significantly more cytotoxic than PBL (p < 0.05). In addition, cytotoxicity against autologous tumor cells was more significantly inhibited by an anti-HLA class I (W6/32) MAb in TIL compared to PBL (p < 0.05). CTL populations derived from TIL and PBL did not lyse autologous EBV-transformed lymphoblastoid cell lines, and showed negligible cytotoxicity against the NK-sensitive cell line K562. Furthermore, in both CD8+ T cell populations the majority of the tumor-specific CTL exhibited a Th1 cytokine bias (IFN-gamma(high)/IL-4(low)). Taken together, these data show that tumor lysate-pulsed mature DC can consistently restore tumor-specific lytic activity in non-cytotoxic breast cancer TIL. These results may have important implications for the treatment of chemotherapy resistant breast cancer with active or adoptive immunotherapy.

The optimal technique for intraoperative pathologic examination of sentinel lymph nodes (SLNs) is still controversial. Recent small series report sensitivity between 60% and 100% for various techniques. The aim of this study was to evaluate our long-term experience with touch preparation cytology (TPC) and frozen section (FS) in the intraoperative examination of SLNs for breast cancer.A total of 247 patients with operable breast cancer underwent an SLN biopsy for staging of the axilla. The SLN was identified by (99m)Tc-labeled sulfur colloid unfiltered dye, blue dye, or both and dissected, and then intraoperative TPC or FS and permanent section, or both, were performed.A total of 479 SLNs were submitted for TPC and permanent hematoxylin and eosin. A total of 68 SLNs were positive by hematoxylin and eosin; 65 SLNs were positive by TPC, with a false-negative rate of 5.8%. The sensitivity for TPC was 94.2%, with a false-positive rate of 0.2%. A total of 165 SLNs were submitted for FS, with a sensitivity of 85.7% and a specificity of 98.6%. The false-positive rate was 1.4%, with a false-negative rate of 15.8%.In a large series, TPC is as accurate as FS but is simpler and faster in the detection of intraoperative metastasis in SLNs for breast cancer.

Breast cancer affects 1 in 8 women today.1 The treatment of breast diseases comprises 14–25% of general surgeons’ practice volume.2,3 Yet, approximately half of all general surgeons perform only two or fewer breast cases per month. Unquestionably, long-term survival after surgery for breast cancer depends upon stage.4 More recently, survival has been linked to performance measures. For instance, survival is greater at hospitals performing greater than 125–150 breast cancer surgeries per year.5–8 Additionally, survival is greater if surgeons perform greater than 15 breast cancer operations per year.8 Finally, completion of a surgical oncology fellowship resulted in a 36% reduction in the risk of death at 5 years when controlled for hospital volume, surgeon volume, age, stage, and race.8–10 Can one infer from these studies that “breast-focused” surgeons are more competent? The criticisms of these studies have been that they often emanate from authors who may be prejudiced toward the results. In fact, there is an observation that, if a surgeon works in a hospital with a cancer center designation, the results from the treatment of breast cancer are not based on any specific surgical or breast disease training other than the general surgical residence.8 The implication would be that the multimodality approach to the treatment of the disease is the reason for any increased survival rather than the judgmental or technical expertise of the surgeon.

The purpose of this study was to determine if race is a factor on overall survival when stage at diagnosis is compared. In this study, a total of 93 women with triple negative breast cancer (TNBC) were evaluated for survival outcomes after diagnosis between the year 2000 through 2010. Thirty-five patients (38%) were African American (AA), and 58 patients (62%) were Caucasian. Overall survival rates were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Student’s t-test was used to calculate differences in cancer recurrence and mortality rates by stage and race. Cox proportional hazards ratios were used to determine the association of patient and variables with clinical outcome. Of women diagnosed with stage 1 breast cancer, the overall survival rates for AAs was 100% compared to Caucasians at 94% (95% CI, 0.003 to 19; P = 0.5). For women with stage 2 breast cancer, overall survival for AA women was 85% and for Caucasian women was 86% (HR = 0.8; 95% CI, 0.3 to 2.6; P = 0.73). For advanced stages (stage 3 and 4), survival for AA women were 78% and 40% for Caucasian women (HR = 0.6; 95% CI 0.2 to 1.98; P = 0.43). Rates of recurrence and mortality were not significantly different between AA and Caucasian TNBC patients. After controlling for patient variables, race was not significantly associated with OS (HR = 1.24; 95% CI, 0.32 to 5.08; P = 0.74) when comparing AA to Caucasian patients. Our study suggests that race does not have an effect on overall survival in African American and Caucasian women diagnosed with TNBC in Arkansas.

Margin negativity is a critical endpoint in breast-conserving surgery. Despite advances in technology, there is up to a 40 % positive margin rate in lumpectomy specimens, which results in a twofold increase in ipsilateral breast tumor recurrence. We have developed a new method for lumpectomy that could improve margin negativity. A novel method for partial mastectomy was developed using ultrasound to perform dissection of breast specimens in real time. Continuous ultrasound-guided breast excision (CUBE) was first tested on gel models and subsequently implemented in vivo. The step-by-step method for this technique was performed on 12 successive patients who had ultrasound-detectable lesions. Twelve patients underwent lumpectomy for cancer using the CUBE technique. All patients had negative margins on final pathology. Three patients who had close margins on ex vivo ultrasound evaluation had additional shave margins taken, resulting in negative final margins. The CUBE technique is a novel technique that allows for dissection of breast lesions with continuous visualization of margins. This facilitates real-time adjustments to ensure margin negativity. Preliminary data is promising, but further research is needed for confirmation.

Excision followed by RFA (eRFA) may allow improved cosmesis while ensuring negative margins in patients with breast cancer. This technique utilizes heat to create an additional tumor-free zone around the lumpectomy cavity. We hypothesized that eRFA will decrease the need for re-excision of inadequate margins.Between July 2002 and January 2005, we conducted a multiphase trial of RFA of prophylactic mastectomy specimens and of women desiring lumpectomy. In both models, a lumpectomy was performed, the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 min. Whole mount slides were used to measure the zone of ablation for ex vivo specimens. Hematoxylin and eosin staining of in vivo lumpectomy margins3 mm was considered inadequate.Nineteen prophylactic mastectomy ablations revealed a consistent perimeter of ablation. Forty-one patients (mean age 63 +/- 14 years) had an average tumor size of 1.6 +/- 1.5 cm underwent in vivo eRFA, and 25% had inadequate margins: one focally positive, one2 mm, eight1 mm and one grossly positive. Only the grossly positive margin was re-excised. Overall complication rate of in vivo ablations was 7.5%. Twenty-four of 41 patients did not have post-eRFA XRT. No in-site local recurrences have occurred during a median follow-up of 24 months (12-45 months). Two patients have occurred elsewhere.The ex vivo ablation model reliably created a 5-10 mm perimeter of ablation. In vivo, this zone reduced the need for re-excision for inadequate margins by 91% (10/11). Short-term follow-up suggests that eRFA could reduce re-excision surgery and local recurrence.