Degnim, AC

Abstract Background: Women with hereditary breast cancer risk, who develop breast cancer, face complex surgical decisions related to their breast cancer and risk to their contralateral breast. The aim of this study was to prospectively evaluate the factors influencing decision making in these women and degree of decision conflict before and after consultation with breast specialized physicians (BSP). Methods: Women with hereditary breast cancer risk and recently diagnosed with unilateral breast cancer were enrolled in a prospective decision making questionnaire study. Questionnaires were completed prior to their initial breast clinic visit and after consultation with a breast clinic physician, nurse educator and a breast surgeon. Results: 68 women completed both questionnaires. Mean age was 52 (range 27–84). Prior to meeting with BSP, 10 (15%) women reported having made a decision for the cancer side and 18 (26%) reported being close to deciding. Of the 20 who expressed a surgical preference prior to consultation, 5 (25%) changed their decision after meeting with the BSP [1 to mastectomy (MTX), 4 to breast conservation (BC)]. After consultation with BSP, 65 (96%) reported having made a decision (BC in 29 (45%), MTX in 35 (54%), unspecified in one). The most commonly cited reasons influencing surgical choice were doctor's advice (79%), family history of breast cancer (74%) and worrisome findings on biopsy (50%). Prior to meeting with BSP, 9 (13%) women reported having made a decision regarding screening and/or risk-reducing options for the contralateral breast and another 11 (16%) reported being close to a decision. The choices in these 20 women were screening only in 10 (50%), contralateral prophylactic MTX (CPM) in 3 (15%), CPM and oophorectomy in 2 (10%), other combinations of options in 4, and unspecified in 1. After meeting with the BSP, 49 (72%) reported having made a decision regarding the contralateral breast; this decision was for screening only in 21 (43%), CPM only in 9 (18%), screening plus tamoxifen in 7 (14%), CPM and oophorectomy in 2 (4%), other combinations of options in 8, and unspecified in 2. The most commonly cited reasons for choices on the contralateral side were: family history (81%), doctor's advice (78%), and worrisome findings on biopsy (43%); only 25% cited psychological or emotional reasons. For both the cancer and contralateral sides, decisional conflict was significantly lower after meeting with BSP than prior to meeting with BSP. Decision-conflict scale total scores (possible range 0–100; higher scores indicate more decisional conflict) summarized for each side and compared between timepoints Conclusion: The BSP consult and family history have the greatest influence on decision making among women with hereditary risk diagnosed with breast cancer. After consultation most women felt they had made decisions for both the cancer and contralateral sides and reported significantly lower decision conflict compared to prior to the consultation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-15-05.

Abstract Purpose: Emerging data from cooperative group trials suggests that not all patients with a positive SLN require completion axillary lymph node dissection (ALND). The controversy regarding who will benefit from additional nodal clearance continues, suggesting a need for improved tools to predict non-SLN involvement. We hypothesized that the size of a SLN metastasis evaluated as a continuous variable would be an important predictor of non-SLN involvement. The goal of this study was to determine clinicopathologic factors including SLN metastasis size that predicted non-SLN involvement and to use these factors to construct an improved predictive nomogram. Methods: Using a prospective database, we identified 509 patients with invasive breast cancer from 1996 - 2007 with a positive SLN who underwent ALND. Patients receiving neoadjuvant therapy were excluded. Clinicopathologic data including age, primary tumor size, presence of multifocal disease, histology (invasive ductal vs. invasive lobular vs. mixed invasive), tumor grade, estrogen receptor, progesterone receptor, and HER2/neu status, presence of lymphovascular invasion (LVI), the number of SLNs identified, number of positive SLNs, the maximum SLN metastasis size and the presence of extranodal extension were recorded. For SLNs described only as containing isolated tumor cells, size was recorded as 0.1 mm. Univariate and multivariate logistic regression analyses were performed to identify factors predictive of positive non-SLNs. Using these variables, a nomogram was constructed and subsequently validated using an external cohort of 464 patients. Results: On univariate analysis, the following factors were predictive of positive non-SLNs: number of SLN identified (p<.001), number of positive SLN (p<.001), maximum SLN metastasis size (p<.001), extranodal extension (p<.001), primary tumor size (p=.001), LVI (p=.019) and histology (p=.034). On multivariate analysis, all factors remained significant at the 5% level except LVI. A nomogram was created using these variables. When applied to an external cohort, the nomogram was accurate and discriminating with an area under the receiver operating characteristic curve of .73 (95% CI: .68 - .77). Conclusions: SLN metastasis size is predictive for identifying additional disease in the axilla. These data have been incorporated into a nomogram that accurately predicts the likelihood of having additional, non-SLN metastasis suggesting that routine reporting of the SLN metastasis size would assist with clinical decision making regarding the need to perform a completion ALND. Figures available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-08.

Abstract INTRODUCTION: Surgical site infection (SSI) is a problematic cause of morbidity following breast/axillary surgery. The breast/axilla has a higher rate of SSI than expected for clean wounds. We evaluated risk factors associated with SSI after breast/axillary operations. Methods: A retrospective review of breast/axillary procedures from July 2004 to July 2006 was performed. SSI was defined using Centers for Disease Control and Prevention criteria, including cases with cellulitis as the only criterion of infection. Data collected included patient demographics, BMI, surgical procedure, ASA class, antibiotic use, drains, and prior radiation (RT). RESULTS: We identified 389 patients who underwent 678 procedures. Thirty-seven SSI (5.5% of procedures) were identified, of which 24 (65%) had only cellulitis. Median time from surgery to SSI diagnosis was 9 days (range 2-112), with 81% occurring in the first 30 days. Univariate analysis identified prior RT, BMI, type of procedure, operative time, use of drain, and postoperative seroma to be associated with SSI (all P<0.05). With multivariate analysis, procedure type remained significant overall (p=0.04). Specifically, mastectomy with sentinel lymph node biopsy (SLNB) and modified radical mastectomy remained significantly associated with higher risk of SSI, with hazard ratios (HR) of 6.3 and 13.5 fold respectively compared to SLNB alone. Seroma (HR 9.0, 95% CI 2.7-29.3), prior RT (HR 3.4, 1.2-9.9), and BMI >=30 (HR 3.1, 1.6-6.2) also remained significantly associated with SSI. CONCLUSION(S): SSI are more frequent after breast/axillary operations than other clean wounds and are associated with prior RT, obesity, more extensive and longer procedures, and postoperative seroma. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-10.

Abstract Background Local recurrence after breast conservation surgery (BCS) varies with clinical risk factors. The aim of this study was to evaluate how local recurrence rates vary by patient age at time of BCS. Methods With IRB approval, all patients undergoing BCS for primary breast cancer between 1988 and 2001 at Mayo Clinic, Rochester were identified. Patients receiving neoadjuvant chemotherapy were excluded. Local recurrence-free survival rates were estimated using the Kaplan-Meier method. Associations with local recurrence-free survival were evaluated using log-rank tests and Cox proportional hazards regression models. Results 3,075 patients underwent 3,143 BCS between 1988 and 2001. Mean age at BCS was 61 years (range 21-98). There were 177 (5.6%) patients aged <40, 496 (15.8%) 40-49, 763 (24.3%) 50-59, 803 (25.6%) 60-69, and 904 (28.8%) who were 70+ years old at time of surgery. At last follow-up, 214 patients (6.9%) experienced a local recurrence at a median of 3.4 years following BCS (range 0.1-14.4). Median follow-up for patients who did not experience a local recurrence was 8.7 years (range 0.0-20.2). The 5-year local recurrence-free survival rate was 95.0%. The frequency of local recurrences by age group were as follows: age <40 — 11.9%; age 40-49 — 5.9%; age 50-59 — 5.9%; age 60-69 — 7.6%; age 70 and older — 6.4%. The 5-year local recurrence-free survival rates for these age groups were 90.0%, 95.4%, 95.6%, 95.4%, and 94.7%, respectively (p=0.041; log-rank test). On univariate analysis, patients <40 years old were nearly twice as likely to experience a local recurrence following BCS compared with patients DCIS was associated with an increased risk of local recurrence compared with T1, T2, T3, or T4 disease (HR 2.25; P<0.001). Factors associated with a decreased risk of local recurrence on univariate analysis included ER positivity (HR 0.46; P<0.001), PR positivity (HR 0.60; p=0.001), adjuvant radiation (HR 0.48; p=0.007) and endocrine therapy (HR 0.65; p=0.012). Multivariate analysis of patients with complete data (n=2126) demonstrated that age <40 and node positivity were associated with an increased risk of local recurrence, while ER positivity, adjuvant radiation and endocrine therapy were associated with a decreased risk of local recurrence. Multivariable analysis of local recurrence after BCS Conclusion Risk factors for local recurrence after BCS include young age, node positivity, ER and PR negativity and absence of adjuvant radiation and endocrine therapy. Patients under age 40 are at increased risk of local recurrence following BCS for breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-02.

Abstract Abstract #62 Background: Breast cancer is the leading cause of cancer deaths in younger women (25 to 49 years of age). Young women with breast cancer also have worse overall survival and increased risk of recurrence compared to older women with breast cancer. Innovative approaches to understanding risk factors and tissue characteristics for the younger population can improve understanding of breast cancer etiology and enhance risk-stratification for these women. This study was aimed at examining breast cancer risk factors among young women (<50 years) with BBD. Materials and Methods: Utilizing the Mayo Clinic Surgical and Pathology Indices, women ages 18 to 85 who had benign excisional breast biopsy between January 1, 1967 and December 31, 1991 were identified. The diagnosis of breast cancer served as the study endpoint and was determined using the Mayo medical record and questionnaire information from study participants. The breast pathologist, blinded to the initial diagnosis and clinical outcome, performed pathology review. BBD was classified as non-proliferative disease (NPD), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). Age-related lobular involution (reduction in number and size of acini per lobule) was classified as none-0%, partial- 1 to74%, or complete- >75% involution. Relative risk (RR) was estimated by comparing the number of observed breast cancers with the number expected, based on breast cancer rates in the Iowa Surveillance, Epidemiology, and End Results registry. Results: Of the 9376 women in the Mayo BBD cohort, 4460 women were aged <50 years at BBD diagnosis and formed the study cohort. The mean age at BBD diagnosis was 39.4 (+ 8.3) years. With a median follow-up of 20 years, 326 breast cancer cases were identified. The histologic findings were NPD in 72% of women, PDWA in 26%, and AH in 2%. The relative risk of breast cancer for the overall cohort of young women with BBD was 1.5 (95% CI [1.4, 1.7]). The relative risk among those with AH was 6.9 (95% CI [4.6, 10.1), compared with a RR of 2.0 (95% CI [1.7, 2.4]) for PDWA, and RR of 1.2 (95% CI [1.0, 1.4]) for NPD. Risk was associated with extent of lobular involution (RR for no involution was 1.7 (95%CI [1.4, 2.1]); partial involution 1.4 (95%CI [1.2, 1.7]); complete involution 0.7 (95%CI [0.3, 1.4]). Family history was available for 83% of the cohort and RR was 2.2 (95% CI [1.7, 2.8]) for women with strong family history and was 1.3 (95% CI [1.1, 1.6]) for women with no family history. Discussion: Young women with BBD are at increased risk of breast cancer. Risk is high in women with atypical hyperplasia, and those with a family history of breast cancer. Lobular involution is associated with reduced breast cancer risk in this population, suggesting a role in modifying breast cancer risk. These findings suggest the need for further research in this population, along with tissue-based studies to examine the processes leading to breast cancer, and enable identification of those women at highest risk. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 62.

Abstract Abstract #3103 Introduction: Lymphedema is well-known in the arm but can also occur in the breast. Diagnosis is currently non-standardized and based on clinical impression. We sought to determine if skin thickness could serve as a useful measure in the diagnosis of breast lymphedema (BLE).
 Methods: Patients undergoing unilateral non-mastectomy procedures were enrolled on this prospective clinical study preoperatively and evaluated for signs and symptoms of lymphedema in the operated breast in the postoperative period. Patients with established BLE were also studied. BLE diagnosis was independent of ultrasound findings and was based on a graded physical exam targeting clinical signs of edema and erythema. Skin thickness was measured with ultrasound at the 6 o'clock position of both breasts. Differences in skin thickness were assessed by the ratio of skin thickness in the operated and contralateral breasts, with comparison of means by two-sample t-test. Receiver operating characteristic curves were constructed to estimate the area under the curve (AUC) and to determine optimal cutpoints.
 Results: Ninety-seven women were studied; 85 were enrolled preoperatively and 12 postoperatively after a diagnosis of BLE. Median length of follow-up overall was 8 months. Of the 97 women, 46 had BLE at one or more follow-up visit with median time to first diagnosis of 3 months. Mean measured skin thickness was 2.3 ± 0.5mm in unaffected breasts and 3.2 ± 1.0 mm in operated breasts. Women with BLE had significantly greater skin thickness in the operated breast compared to the contralateral breast, with a mean skin thickness ratio of 1.83 ± 0.57 in patients with BLE compared to 1.18 ± 0.40 among those without BLE (p<0.0001). Skin thickness ratio provided excellent discrimination for BLE, with an area under the curve (AUC) of 0.86. At a ratio of 1.32 or greater (32% greater skin thickness in operated versus contralateral breast), sensitivity and specificity for diagnosing BLE were 81% and 82% respectively. A single measure of skin thickness in the operated breast also correlated well with diagnosis of BLE, with skin thickness of 3.2 mm or greater demonstrating sensitivity of 78% and specificity of 82%, AUC 0.82.
 Conclusions: Breast lymphedema results in skin edema and increased skin thickness that can be quantified with ultrasound. Measuring breast skin thickness- either as a single reading or as a ratio to the unaffected breast- may be useful in the diagnosis of breast lymphedema. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3103.

Abstract Abstract #1005 Background: Several models for the prediction of non-sentinel lymph node metastasis (+NSLN) in sentinel lymph node positive (+SLN) breast cancer patients have been published. Multiple variables have been shown to be important in prediction of +NSLN. To this date, models that utilize 7-8 variables have been significantly more discriminatory than models using only 2-3 variables. In this study, we evaluate the performance of the newly created Stanford online calculator (SOC) to predict the likelihood of +NSLN. The SOC uses 3 variables: primary tumor size, sentinel lymph node metastasis size, and presence/absence of lymphovascular invasion.
 Methods: From 1997-2004, 465 breast cancer patients with clinically negative axillae were found to have a +SLN and underwent completion axillary lymph node dissection (ALND) at the Mayo Clinic. Using the SOC the probability of having +NSLN was determined for each patient. Complete variable data was available for 464 patients which make up the cohort reported here. A receiver-operating characteristic (ROC) curve was created and the area-under-the-curve (AUC) was calculated. Mean probabilities of patients with and without +NSLN were compared. Additionally, patients with a low Stanford probability were examined to determine the model's accuracy in discriminating patients who could potentially be spared ALND. These results were compared to the results of the Mayo Clinic and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms which have been previously applied to this same cohort of patients.
 Results: The AUC of the Stanford model was 0.72 (95% CI 0.67-0.77). The mean Stanford probabilities for patients with and without NSLN disease were 0.75 (range 0.06 to 1.0) and 0.50 (range 0.05 to 1.0), respectively (p < 0.0001). Examining patients with a Stanford probability <= 10%, we found that 47 patients met this criterion; 6 had +NSLN and 41 did not, for a false negative (FN) prediction rate of 13%. There was only 1 patient with Stanford probability <= 5%, and this patient did not have +NSLN. The AUC of the MSKCC and Mayo nomograms in this same patient population was 0.74 and 0.77, respectively. The AUCs did not differ significantly (p = 0.13) among the 3 models.
 
 Conclusion: Despite using only three variables, the Stanford nomogram appears to perform as well as, but not better than the MSKCC and Mayo nomograms in our patient cohort. Further validation in other patient populations is needed prior to widespread utilization of this nomogram. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1005.