#1018 Background: Sentinel lymph node (SLN) biopsy has become the standard of care for the evaluation of axillary metastasis in breast cancer. The accurate determination of metastasis in SLNs at the time of surgery is required in order to properly select those patients who should undergo axillary node dissection (AND).
 Methods: We performed a retrospective review of 402 breast cancer patients who underwent SLN biopsy with evaluation of 931 nodes by touch prep from June 2000 through January 2007. Results of touch prep diagnosis at the time of surgery were compared to final pathologic evaluation by permanent H&E. All false negative (FN) results were re-reviewed to determine possible reasons for errors in diagnosis.
 Results: At least one SLN was successfully identified in 379 patients. Of 68 patients with a true positive SLN, all underwent AND and in 46% the SLN was the only node in which metastases were identified. A total of 32 patients (8.44%) had at least one FN result. In 931 nodes evaluated, there were 38 (4.1%) FN results and no false positives. There were no significant differences between FN results in patients with invasive ductal cancer (26 of 284 patients, 4.3% nodes) compared to invasive lobular cancer (5 of 46 patients, 5.6% nodes). The remaining patients had DCIS or other primary diagnosis with two FN SLNs. Of the 38 SLNs with a FN result, 30 (79%) had only micromets on permanent H&E. Of the remaining 8 SLN with a FN touch prep, 3 of 703 SLNs (0.4%) occurred with invasive ductal cancer and 4 of 108 SLNs (3.7%) occurred with invasive lobular cancer, demonstrating a significant difference, p=0.01. In the 32 patients with a FN SLN result, 19 patients underwent completion AND and in 12 patients (63%), the SLNs were the only nodes with cancer. Examining the 19 patients with FN SLN who underwent completion AND, 14 patients had invasive ductal cancer with only 4 (29%) having cancer found in non-SLN compared to 5 patients with invasive lobular cancer with 3 (60%) having cancer in non-SLN. Touch prep evaluation of SLN in breast cancer had an overall sensitivity of 72%, specificity of 100%, positive predictive value of 100% and negative predictive value of 95.4%. The cost for touch prep is $32 less per node compared to frozen section or an average cost reduction of $74 per patient.
 Conclusion: The accuracy of touch prep for the evaluation of SLN in breast cancer compares favorably to the reported results for frozen section with a lower cost. In patients with a FN SLN result, the SLNs are likely to be the only nodes involved with metastases, especially if the SLN is found to have only micromets. However, patients with invasive lobular cancer were more likely to have a FN finding in the setting of marcomets and were more likely to have metastases in non-SLNs. Patients with invasive lobular cancer who have a negative SLN by touch prep should have the SLN evaluated by frozen section to confirm the diagnosis. The data also suggest that patients with invasive lobular cancer and a FN SLN by touch prep may benefit from AND. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1018.

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Background: Women with breast cancer increasingly choose to undergo contralateral prophylactic mastectomy (CPM) even as the benefit of this procedure for woman at average risk for breast cancer remains uncertain. Many women with newly diagnosed breast cancer undergo pre-operative MRI for a variety of indications. Growing evidence suggests that obtaining a pre-operative MRI increases the likelihood that a patient will choose CPM. This study evaluates the relationship between a pre-operative MRI and the decision to pursue CPM, as well as the rate of contralateral MRI findings for which follow-up is recommended and the choice to undergo CPM. The pathology found in contralateral breasts in this series is also reported. Methods: Newly diagnosed breast cancer patients were prospectively enrolled in Breast Molecular Epidemiology Resource (B-MER) observational study at the University of Iowa from April 2010 through March 2013. Prophylactic mastectomy is defined as removal of the contralateral breast within 12 months of definitive mastectomy. Univariate logistic regression was used to identify factors predictive of undergoing CPM. Recommended follow-up of the contralateral breast MRI is defined as any imaging or procedure other than immediate ultrasound evaluation. Results: Among 134 patients (mean age 53) who underwent mastectomy, 53 (40%) underwent CPM. Univariate analysis revealed that patients undergoing CPM were more likely to have had a preoperative bilateral MRI (52%% vs. 28%, p = 0.006) and were more likely to have been given a recommendation for a follow-up test (79% vs, 40%, p = 0.007). Univariate Analysis of Odds of Electing to Undergo CPMVariableLevelOdds ratioP-valueAge5 year0.62<.001Breast MRIYes vs No2.740.006MRI follow-up recommendationYes or No5.530.007Nodal statusPositive vs Negative0.820.581History of benign breast biopsiesNo vs Yes1.850.209Family history of breast cancerYes vs No1.160.711ER/PR statusNegative vs Positive1.830.134Triple NegativeNo vs Yes1.910.196HER2 statusPositive vs Negative2.470.066BRCA testing doneYes vs No6.04<.001BRCA results*Positive vs Negative3.120.315Tobacco everYes or No1.390.354Alcohol everYes or No1.250.544* Indeterminate and not done levels were excluded from the analysis Univariate analysis also revealed associations between choice of CPM and younger age (p<0.001) and BRCA testing (p<0.001). In this series, CPM was not associated with nodal status, ER/PR status, history of benign breast biopsies, family history of breast cancer, BRCA result and tobacco or alcohol use, although there was a trend for association with HER2 status. Of the 53 patients who underwent CPM, one had proliferative disease with atypia, 34 had proliferative disease without atypia. A single patient had DCIS found in the contralateral breast which had not been identified on MRI. Conclusions: The use of preoperative breast MRI and abnormal imaging findings in the contralateral breast, for which follow-up was recommended, led to a higher CPM rate. Contralateral prophylactic mastectomy rarely uncovered occult malignancy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-02-07.

Introduction: ECM1 is known to be over-expressed in multiple tumor cell lines and primary tumors, including breast cancers. ECM1 overexpression is also an independent predictor of poor prognosis in primary breast carcinomas. While similar associations have also been reported in other tumors, the mechanisms by which ECM1 affects prognosis have not been elucidated. Methods: ECM1 was silenced in the Hs578t and MDA-MB231 breast cancer cell lines using siRNA. The cells were evaluated for morphological changes, migration (wound-healing assay, TScratch program), matrigel invasion and cell attachment. Real Time RT-PCR using a 94-geneTumor Metastasis Array (TaqMan), was performed to assess the effects of ECM1 downregulation on in Hs578t cells. Alterations in RNA expression were validated at the protein level using western blots. Differences between groups were evaluated using the student's t-test and p<0.05 was considered statistically significant. Results: ECM1 silenced cells demonstrated altered morphology with a more elongated appearance to the cells, when compared those transfected with non-targeting siRNA. Reduced cell migration was noted for both silenced Hs578t and MB231 cell lines (both p<0.0001). Matrigel invasion was reduced in the Hs578t cell line only (p<0.002). however, cell attachment was decreased in both cell lines. (p <0.0001 for Hs578t, and < 0.01 for MB231). ECM1 downregulation affected the expression of several metastasis associated genes including CD44, Metalloproteinase-2, fibronectin at the RNA level. CD44 expression was significantly reduced in ECM1-silenced cells by western blot. Conclusion: ECM1 appears to be involved in maintenance of tumor cell shape, migration, invasion and attachment properties in the cell lines tested, and also affects expression of CD44 protein, a known tumor prognostic factor. ECM1 may be a key molecule affecting tumor progression and metastasis, which is a complex process involving these components. Our findings suggest mechanisms by which ECM1 overexpression may affect tumor prognosis. Further work is needed to evaluate if altering ECM1 expression may be a novel therapeutic option for these tumors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-04-16.

Node negative microscopically invasive breast cancer (BC) is frequently associated with ductal carcinoma in situ (DCIS) and considered to have a similar prognosis. We evaluated women with T1micN0M0 (T1mic), DCIS and Stage I BC and report clinical characteristics, risk for subsequent contralateral breast cancer (CBC) and overall survival (OS). Methods: The study cohort included women diagnosed 1998-2012 and reported to Surveillance, Epidemiology, and End Result (SEER) data with DCIS, T1mic, or Stage I BC (not including T1mic). Subsequent CBCs were identified in patients with known laterality without contralateral mastectomy. Kaplan Meier models were used to estimate survival and time to CBC. Log-rank tests assessed differences in survival across groups Results: During the study period, 9,785 women were diagnosed with T1mic. Clinical features and risk of CBC are shown in the Table 1. Women with DCIS and T1mic were younger than those with Stage I BC. T1mic was more likely to be hormone receptor (HR) negative. Women with T1mic underwent mastectomy significantly more often than women with DCIS or Stage 1 BC. T1mic occurred more frequently in non-white women. Women with T1mic were significantly more likely to develop subsequent CBC than women with Stage 1 BC with a trend for increased CBC compared to women presenting initially with DCIS. Of those who develop CBCs 5.9% (DCIS), 11.2% (T1mic), and 14.6% (Stage 1) developed within 1 year (YR) of diagnosis of the index cancer. At 10 YRS these numbers were 73.7%(DCIS), 82.7%(T1mic) and 83.2% (Stage 1) (DCIS vs T1mic, p<0.001 T1mic vs Stage 1, P= 0.048). At 10 YRS OS for women with CBC after initial BC was 89.5%(DCIS), 86.6%(T1mic) and 84.3%(Stage1) (DCIS vs T1mic, p=0.077, T1mic vs Stage1 p=0.293), Table 2. Table 1 DCIS, T1mic, Stage I BC: Clinical Features and Contralateral Breast Cancer DCIST1micStage 1 (excluding T1mic)   %%%p ^p ^^N49,6829,785248,307  Median Age5858620.719<0.001HR positive85.0%72.8%86.5%<0.001<0.001Grade     Well-moderately differentiated56.3%61.1%76.6%  Poorly-undifferentiated43.7%38.9%23.4%<0.001<0.001Mastectomy22.7%36.7%24.1%<0.001<0.001Race     White79.7%77.3%84.2%  Black10.8%11.0%7.9%<0.001<0.001Other9.4%11.6%7.9%  CBC*4.1%4.3%3.4%0.317<0.001CBC**57.9%72.9%77.0%<0.0010.021* Portion of full sample, **Of those who had a subsequent BC (ipsilateral or contralateral),^ DCIS vs T1mic,^^ stage I vs T1mic Table 2 OS by Initial Stage and with CBC  5 YR10 YRp*  OSOS DCISall97.3%88.4%  develop CBC97.8%89.5%0.037T1micall96.3%88.9%  develop CBC95.0%86.6%0.036Stage1 (excluding T1mic)all95.9%85.0%  develop CBC86.9%84.3%0.001*Comparing survival of the stage cohort (all) with women diagnosed with that stage who develop CBC Conclusion: Women with T1mic were at increased risk for subsequent CBC relative to women with Stage I BC. When subsequent CBC occurred it developed earlier in women with T1mic than those with DCIS. Time course for this second event and survival with CBC at 10 years matched more closely with women diagnosed with Stage 1 BC. These findings offer suggestions about the biology of T1mic and may have implications for counseling these women on risk reducing strategies. Citation Format: Thomas A, Weigel RJ, Leone JP, Spanheimer PM, Schroeder MC. Increased risk of contralateral breast cancer after diagnosis of microscopically invasive breast cancer: SEER 1998-2012. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-24.