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21.10. Breast Cancer Histology And The Influence Of TheHormonal Milieu. J. R. Nitzkorski,1 F. Zhu,2 C. E.Loveland-Jones,3 L. Sesa,1 E. A. Ross,2 E. R. Sigurdson,1

R. J. Bleicher1; 1Department of Surgical Oncology, FoxChase Cancer Center, Philadelphia, PA; 2Department ofBiostatistics, Fox Chase Cancer Center, Philadelphia, PA;3Department of Surgery, Temple University Hospital,Philadelphia, PA

Introduction: Although greater exposure to endogenous hormonesand to hormone replacement therapy (HRT) increases the risk of de-veloping breast cancer, and HRT usage is associated with pathologicfindings, little is known about the impact of differences in the lengthof HRT use and chronology of exposure on the innate characteristicsof the primary tumor. Methods: A prospectively collected IRB-approved breast cancer database containing 4,257 breast cancer pa-tients was retrospectively reviewed. Patients having oophorectomieswere eliminated. Demographics, HRT usage and chronology, andmenopausal status were reviewed. Innate primary tumor character-istics alone were correlated to avoid the confounders of screeningdifferences, lead time, and length bias upon stage. Charts were re-reviewed for the date of menarche and menopause. Total hormonalexposure (THX) was defined as the time from menarche to meno-pause plus any time on HRT. Results: There were 403 postmeno-pausal patients identified between 2004 and 2008, among whom75.6% of tumors were ER positive (+), 61.5% PR+, and 22.1% highgrade. HER2/neu was overexpressed on IHC in 18.6% of patientsand invasive ductal and lobular carcinomas comprised 76.9% and16.4% of cases, respectively. Median duration of endogenous hor-monal (menarche to natural menopause) and HRT exposure was38y and 5y, respectively. Median THX was 39y in both ER+ andER- tumors (p¼0.58). HRT exposure was similar prior to developingprimary tumors that were ER+ and ER- (4 and 5 years, respectively,p¼0.28). Univariate predictors of ER positivity included white race(p<0.0001), lobular histology (p<0.0001), and lack of HER2/neuoverexpression (p<0.0001). ER-positive tumors were more likely tobe present in patients having HRT when on HRT at diagnosis(p¼0.03). When adjusted for age and race, no differences were foundin histology, ER positivity, PR positivity, grade and HER2/neu sta-tus based upon the duration of THX, or the duration of HRT. In con-trast, in those using HRT, use at diagnosis predicted ER-positivity(p¼0.011) but not PR status, HER2/neu overexpression, grade, orhistology. These factors were also not affected by an increasing du-ration between the end of THX and diagnosis, during which therewas no hormonal exposure. Conclusion: Although longer hormonalexposure (natural or HRT) increases the risk of breast cancer devel-opment, the duration of THX, the duration of HRT, and the intervalbetween hormonal exposure and cancer diagnosis did not affect theinnate characteristics of the tumor. These findings may affect HRTdecision making in those without breast cancer who have chosento have HRT, and may assist in preoperative discussions with thosewho develop breast cancer regarding its impact upon the expectedpathology.

ONCOLOGY 2: CLINICAL OUTCOMES &BIOMARKERS

22.1. The Influence Of Preoperative MRI On Breast CancerTreatment. B. T. Miller, A. M. Abbott, T. M. Tuttle; Depart-ment of Surgery, University of Minnesota, Minneapolis, MN

Introduction: The use of breast magnetic resonance imaging (MRI)for preoperative imaging and operation planning has been increasing.The aims of this study were to evaluate the rates of mastectomy andbreast conserving surgery (BCS) in patients who undergo preoperativeMRI for early stage breast cancer, and to determine patient and tumorcharacteristics that predicted treatment choice. Methods: We con-

ducted a retrospective review of 418 patients who underwent initialsurgical treatment for breast cancer at the University of MinnesotaMedical Center between 2002 and 2009. Exclusion criteria included:stage IV disease, previous breast cancer, lobular carcinoma in situ,Hodgkin’s lymphoma, or positive BRCA status.Univariate analysiswas used to evaluate differences in patient demographics, surgicalmanagement, and tumor characteristics of women who received mas-tectomy compared to BCS. Multiple logistic regression was used toidentify independent predictors for mastectomy. Results: Among the418 patients that met inclusion criteria, 222 (53%) patients receivedpreoperative MRI and 196 (47%) patients did not receive MRI. Wefound that patients who receivedMRI had higher rates of mastectomythan patients who did not haveMRI (44% vs 29%; p¼0.001). Multivar-iate analysis of 406 patients with known estrogen receptor (ER) statusrevealed that tumor size, lymph node status, infiltrating lobular carci-noma, and pretreatmentMRIwere independent predictors for mastec-tomy (p<0.01) (Table). Patients who had anMRI were 1.78 timesmorelikely tohaveamastectomy thanpatientswithout anMRI (95%CI1.13to 2.79) Family history of breast cancer, ER status, and invasive (vs.noninvasive) carcinoma were not significantly predictive for mastec-tomy. Patients who had a preoperative MRI were more likely to haveadditional biopsies than patients who did not receive MRI (p<0.001),andMRIdetectedoccult contralateral breast cancer in2.7%ofpatients.Additionally, among patients treatedwith BCS, thosewith no preoper-ativeMRI did not have higher re-excision rates or increased ipsilateralbreast tumor recurrences than patients with preoperative MRI. Con-clusion: The use of preoperative MRI significantly influences breastcancer treatment; we found that preoperative MRI was associatedwith higher rates of mastectomy, synchronous contralateral breastcancers, and additional breast biopsies.

TABLEMultivariate Logistic Regression Results for Predictors of

Mastectomy

Odds Ratio 95% CI P

Family History

Positive v negative 1.4 0.9 to 2.3 0.17 Unknown v negative 0.7 0.1 to 6.6 0.75

LN status

Positive v negative 2.5 1.5 to 4.2 <0.001

ER status

Negative v positive 1.3 0.8 to 2.3 0.30

Tumor size

<2 cm v 2-5 cm 0.6 0.4 to 0.9 0.03 2-5 cm v>5 cm 20.1 2.5 to 165 0.005

MRI

Yes v no 1.8 1.1 to 2.8 0.01

Infiltrating carcinoma

Yes v no 1.2 0.6 to 2.5 0.55

ILC

Yes v no 0.3 0.1 to 0.6 <0.001

Abbreviations: CI, confidence interval; LN, lymph node; ER, estro-gen receptor; MRI, magnetic resonance imaging; ILC, infiltrating lob-ular carcinoma.

22.2. Is There aMolecularBasis forCancerGenderDisparity?R. Rahbari, L. Zhang, E. Kebebew; National Cancer Institute,Bethesda, MD

Introduction: Cancer gender disparity in incidence, disease aggres-siveness, response to therapy, and prognosis has been observed fora variety of cancers, but the cause of the disparity is poorly under-stood. Thyroid cancer is one such cancer for which gender disparityin incidence, aggressiveness and prognosis is well established.

ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS 221

Dietary, environmental and reproductive factors, and frequent acti-vating somatic mutations do not appear to have a significant role incancer gender disparity of the most common type of thyroid cancer(papillary thyroid cancer, PTC). We postulated that the gender dis-parity in PTC is due to yet unidentified molecular factors. We testedthis hypothesis by application of genome wide gene expression analy-sis to identify, validate and study target genes that are expressed dif-ferentially betweenmen andwomen in PTC.Methods:Genome-widegene expression analysis in 35 samples of PTC (21 women versus 14men matched for age and stage of cancer) was conducted. In orderto identify gene that were not on the Y-chromosome or involved inX-chromosome inactivation, target genes were cross-validated usinga genome-wide gene expression dataset from adrenocortical neo-plasms (86 samples, 56 women and 30 men). Quantitative PCR wasused to further validate the candidate genes identified and to deter-mine changes specific to PTC using normal thyroid (18 samples, 14women and 4 men) and non-thyroid tissue samples(12 samples, 6women and 6 men). The effects of estrogen and testosterone on theidentified candidate genes were examined in thyroid cancer (TPC-1,FTC-133) and breast cancer (MCF-7) cell lines using quantitativePCR. Results: We found complete clustering of PTC by gender onunsupervised cluster analysis. We identified 42 genes that were dif-ferentially expressed between men and women PTC (p<0.01, B>0).Cross-validation to adrenal neoplasm genome wide gene expressiondataset identified 10 genes that were not X- and Y-linked. Two candi-date genes (CDC23, SFRP2) and an X-linked gene (XIST) were ana-lyzed to further confirm differences in gene expression were specificto PTC. There was no difference in expression of CDC 23 (p¼0.69)and SFRP2 (p¼0.41) between normal thyroid tissue and parathyroidneoplasms by gender, while the control XIST gene was differentiallyexpressed by gender (p¼0.0004). Sex hormone effect on gene expres-sion of the 10 candidate genes in cell lines showed a significant changefor one of the 10 candidate genes: a 4.6 fold increase in expression ofCXCL14 (10nM testosterone compared to vehicle, P<0.01), anda 16.7 fold increase in expression of CXCL14 (10nM 17-Estradiol com-pared to vehicle, P<0.01) at 48 hours.Conclusion:To our knowledge,this is the first study to demonstrate a difference in gene expressionprofile in cancer by gender. These gene expression changes appearto be specific to PTC. CXCL14 expression is regulated by sex hor-mones and my play a role in tumor cell biology in PTC.

22.3. Obesity Is A Predictor ofMorbidity In 1,629 Patients Un-dergoing Adrenalectomy. H. S. Kazaure,1 D. C. Thomas,2

S. A. Roman,1 J. A. Sosa1; 1Yale University School of Medicine,New Haven, CT; 2SUNY Upstate Medical University,Syracuse, NY

Introduction: There is a paucity of literature evaluating the effectsof obesity on patients undergoing adrenalectomy. This study is thefirst to examine the impact of obesity, asmeasured by bodymass index(BMI), on 30-day clinical and economic outcomes of adrenalectomy ina multi-institutional database. Methods: Adult patients (�18 years)who underwent adrenalectomy in ACS-NSQIP 2005-08 were identi-fied. Patients were classified into groups by BMI: normal weight(BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9kg/m2), obese (BMI30-34.9kg/m2) andmorbidly obese (BMI� 35 kg/m2). Independent pa-tient variables included gender, race, age and surgical procedure. Pa-tient comorbidity was assessed by functional health status, ASA class,and presence/absence of �35 comorbidities, including Cushing’s syn-drome/disease, diabetes and hypertension. Clinical outcomes in-cluded complications, 30-day return to the OR and mortality.Economic outcomes were total time in the OR and hospital length ofstay (LOS). Higher BMI groups were compared to normal BMI groupusing c2, ANOVA with posthoc Bonferroni test, and multivariate lin-ear/logistic regression.Results: 1,629 patients underwent adrenalec-tomy: 62% were female, 76% white, 50% aged 45-65 yrs, 82% hadlaparoscopic adrenalectomy and 2% had bilateral procedures. 72%and 19% of patients had hypertension and diabetes, respectively.

Patientswere evenly distributed acrossBMI groups. BMI distributionwas similar by procedure type. Compared to normal weight patients,obese andmorbidly obese patients weremore likely to have longer ORtimes (198min vs. 214min, 226min, p<0.05 and p<0.001 respectively)and have � 1 wound complication (0.2% vs. 0.4%, 1.2%, p<0.001), in-cluding superficial and deep wound infections (p<0.001, p<0.01 re-spectively). Morbidly obese patients were more likely to sustainsuperficial wound infections (p<0.01) after a laparoscopic procedure,and deep wound and urinary tract infections (p<0.05) after an openprocedure. Wound complications did not occur more frequently inCushing’s patients or those undergoing bilateral surgery. Incidenceof complications was higher in open vs. laparoscopic adrenalectomy(17.0% vs. 5.2%, p<0.001). On multivariate analysis, morbid obesitywas predictive of having�1 overall complications (Adjusted Odds Ra-tio: 2.9, p¼0.001), wound-specific (Adjusted Odds Ratio: 6.1, p<0.01)and septic complications (Adjusted Odds Ratio: 3.1, p<0.05). Obesityof any degree was predictive of longer OR times (p<0.01).There wereno differences in rates of reoperation, hospital LOS, and 30-day mor-tality across BMI groups.Conclusion:Obese andmorbidly obese pa-tients undergoing adrenalectomy have more morbidity than normalBMI patients. In particular, morbidly obese patients are at increasedrisk of sustaining wound and septic complications. High BMI is an in-dependent risk factor which needs to be considered in surgical deci-sions regarding adrenalectomy.

22.4. Cost-Effectiveness Analysis Of Repeat FNA For ThyroidBiopsies Read As Atypia Of Undetermined Significance.M. B. Heller,1 K. Zanocco,1 S. Zydowicz,2 D. Elaraj,1 R. Nayar,2

C. Sturgeon1; 1Northwestern University Feinberg School ofMedicine, Department of Endocrine Surgery, Chicago, IL;2Northwestern University Feinberg School of Medicine,Department of Cytopathology, Chicago, IL

Introduction: The 2007 National Cancer Institute (NCI) ThyroidFine Needle Aspiration (FNA) State of the Science Conference pro-posed a 6 tiered classification scheme for thyroid FNA. The indetermi-nant category was partially replaced by a new category ‘‘Atypia ofUndetermined Significance’’ (AUS). The malignancy rate for AUSFNAs should be between 5 and 10%. In the absence of risk factorsor radiographic features of thyroid cancer, repeat FNA in 3-6 monthsis recommended. We found that from 2000-2009, 28% of thyroid nod-ule FNAs at our institution initially read as AUS had no repeat FNAand no surgical resection, 43% went directly to surgery, and 29% hadrepeat FNA. 53% of nodules initially categorized as AUS were benignon repeat FNA. 34% remained AUS on repeat FNA, and the malig-nancy rate in this group was 21%. We hypothesized that repeatFNA would be more cost-effective than diagnostic lobectomy afteran initial AUS FNA result, and compliance with repeat FNA recom-mendations would be a cost-saving measure and improve cancer de-tection rates. Methods: Cost-effectiveness analysis was performedcomparing diagnostic lobectomy with repeat FNA for lesions initiallyclassified asAUS.AMarkovmodelwas developedbased ona referencecase scenario of a 40 year oldwith a solitary nonspecific nodule read asAUS by FNA. A third-party payer perspective was used. Treatmentoutcomes and probabilities for each strategy were identified basedon literature review. Costs were estimated in 2009 US dollars usingMedicare charge and reimbursement data and the USNationwide In-patient Sample. It was assumed that total thyroidectomy or comple-tion thyroidectomy would be performed for thyroid carcinoma. Thecost of lifelong thyroid hormone was included. Outcomes wereweighted using established quality of life utility factors in order toyield quality-adjusted life years (QALYs) as a measure of effective-ness. All future costs and QALYs were subjected to a 3% annual dis-count rate. Sensitivity analysis was used to examine theuncertainty of probability, cost, and utility estimates in the model.Results: The diagnostic lobectomy strategy cost $6,140 and produced23.971 QALYs. Repeat FNA for AUS cost $1,225 and produced 24.042