Isabelle Bedrosian

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (110)596.83 Total impact

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    ABSTRACT: Previous studies suggested that sentinel lymph node (SLN) identification rates are lower in older breast cancer patients. This study was undertaken to compare identification rates in patients 70 years of age and older versus those younger than 70 years in a large cohort undergoing sentinel lymph node dissection (SLND). Patients undergoing SLND between August 1993 and December 2006 were identified and grouped by age. Clinicopathologic data and details regarding the procedure were reviewed. Of the 3995 patients undergoing SLND, 3406 (85.3%) were under 70 years of age, and 589 (14.7%) were 70 years or older. Age was significantly associated with clinical stage (P = .001) and tumor grade (P < .0001). A greater proportion in the older group had clinical stage I disease (74.7% vs. 66.8%), and a lower proportion had grade 3 tumors (24.0% vs. 36.1%). There were no significant differences by age in the mapping method or site of injection. Overall SLN identification rate was 97.2% and did not differ significantly by age. The SLN was positive in 23.1% of younger patients and 18.2% of older patients (P = .01). Sentinel lymph node dissection can be performed with high identification rates regardless of patient age. Breast cancer patients 70 years and older with clinically negative axillary lymph nodes should be offered SLND, as the presence of lymph node metastasis may alter adjuvant therapy recommendations.
    Clinical Breast Cancer 12/2010; 10(6):477-82. · 2.42 Impact Factor
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    ABSTRACT: The lack of large panels of validated antibodies, tissue handling variability, and intratumoral heterogeneity potentially hamper comprehensive study of the functional proteome in non-microdissected solid tumors. The purpose of this study was to address these concerns and to demonstrate clinical utility for the functional analysis of proteins in non-microdissected breast tumors using reverse phase protein arrays (RPPA). Herein, 82 antibodies that recognize kinase and steroid signaling proteins and effectors were validated for RPPA. Intraslide and interslide coefficients of variability were <15%. Multiple sites in non-microdissected breast tumors were analyzed using RPPA after intervals of up to 24 h on the benchtop at room temperature following surgical resection. Twenty-one of 82 total and phosphoproteins demonstrated time-dependent instability at room temperature with most variability occurring at later time points between 6 and 24 h. However, the 82-protein functional proteomic "fingerprint" was robust in most tumors even when maintained at room temperature for 24 h before freezing. In repeat samples from each tumor, intratumoral protein levels were markedly less variable than intertumoral levels. Indeed, an independent analysis of prognostic biomarkers in tissue from multiple tumor sites accurately and reproducibly predicted patient outcomes. Significant correlations were observed between RPPA and immunohistochemistry. However, RPPA demonstrated a superior dynamic range. Classification of 128 breast cancers using RPPA identified six subgroups with markedly different patient outcomes that demonstrated a significant correlation with breast cancer subtypes identified by transcriptional profiling. Thus, the robustness of RPPA and stability of the functional proteomic "fingerprint" facilitate the study of the functional proteome in non-microdissected breast tumors.
    Clinical Proteomics 12/2010; 6(4):129-51.
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    ABSTRACT: Complete axillary lymph node dissection (ALND) after a positive sentinel lymph node biopsy (SLNB) remains the standard practice. As nodal surgery has long been considered a staging procedure without a clear survival benefit, the need for ALND in all patients is debatable. The purpose of this study was to examine differences in survival for patients undergoing SLNB alone versus SLNB with complete ALND. Patients with breast cancer who underwent SLNB and were found to have nodal metastases were identified from the Surveillance, Epidemiology, and End Results database (1998-2004). Clinicopathologic and outcomes data were examined for patients who underwent SLNB alone versus SLNB with ALND. We identified 26,986 patients with disease-positive lymph nodes; 4,425 (16.4%) underwent SLNB alone, and 22,561 (83.6%) underwent SLNB with ALND. Patients were significantly more likely to undergo SLNB alone if they were older (median 59 years old) or if the tumor was low grade and estrogen receptor positive. From 1998 to 2004, the proportion of patients with micrometastasis in the sentinel lymph nodes who underwent SLNB alone increased from 21.0 to 37.8% (P < 0.001). At a median follow-up of 50 months, there were no statistically significant differences in overall survival (OS) between patients who underwent SLNB alone versus complete ALND. There is an increasing trend toward omitting ALND in patients with micrometastatic nodal disease identified by SLNB. Compared with SLNB alone, completion ALND does not seem to be associated with improved survival for breast cancer patients with micrometastasis in the sentinel lymph nodes.
    Annals of Surgical Oncology 10/2010; 17 Suppl 3:343-51. · 4.12 Impact Factor
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    ABSTRACT: We sought to evaluate the utilization of blue dye in addition to radioisotope and its relative contribution to sentinel lymph node (SLN) mapping at a high-volume institution. Using a prospectively maintained database, 3,402 breast cancer patients undergoing SLN mapping between 2002 and 2006 were identified. Trends in utilization of blue dye and results of SLN mapping were assessed through retrospective review. Statistical analysis was performed with Student t test and chi-square analysis. 2,049 (60.2%) patients underwent mapping with dual technique, and 1,353 (39.8%) with radioisotope only. Blue dye use decreased gradually over time (69.8% in 2002 to 48.3% in 2006, p < 0.0001). Blue dye was used significantly more frequently in patients with lower axillary counts, higher body mass index (BMI), African-American race, and higher T stage, and in patients not undergoing skin-sparing mastectomy. There was no difference in SLN identification rates between patients who had dual technique versus radiocolloid alone (both 98.4%). Four (0.8%) of 496 patients who had dual mapping and a positive SLN had a blue but not hot node as the only involved SLN. None of these four had significant counts detected in the axilla intraoperatively. Nine (0.4%) of 2,049 patients who had dual mapping had allergic reactions attributed to blue dye. Blue dye use has decreased with increasing institutional experience with SLN mapping. In patients with adequate radioactive counts in the axilla, blue dye is unlikely to improve the success of sentinel node mapping.
    Annals of Surgical Oncology 10/2010; 17 Suppl 3:280-5. · 4.12 Impact Factor
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    ABSTRACT: Increasing numbers of women with breast cancer are electing for contralateral prophylactic mastectomy (CPM) to reduce the risk of developing contralateral breast cancer. The objective of this study was to identify factors that may affect a patient's decision to undergo CPM. We identified 2,504 women with stage 0 to III unilateral primary breast cancer who underwent breast surgery at our institution from January 2000 to August 2006 from a prospectively maintained database. We did logistic regression analyses to determine which factors were associated with undergoing CPM. Of 2,504 breast cancer patients, 1,223 (48.8%) underwent total mastectomy. Of the 1,223 patients who underwent mastectomy, 284 (23.2%) underwent immediate or delayed CPM. There were 33 patients (1.3%) who had genetic testing before the surgery, with the use of testing increasing in the latter years of the study (0.1% in 2000-2002 versus 2.0% in 2003-2006; P < 0.0001). Multivariable analysis revealed several factors that were associated with a patient undergoing CPM: age younger than 50 years, white ethnicity, family history of breast cancer, BRCA1/2 mutation testing, invasive lobular histology, clinical stage, and use of reconstruction. We identified specific patient and tumor characteristics associated with the use of CPM. Although genetic testing is increasing, most women undergoing CPM did not have a known genetic predisposition to breast cancer. Evidence-driven models are needed to better inform women of their absolute risk of contralateral breast cancer as well as their competing risk of recurrence from the primary breast cancer to empower them in their active decision making.
    Cancer Prevention Research 08/2010; 3(8):1026-34. · 4.89 Impact Factor
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    ABSTRACT: We sought to determine present-day locoregional recurrence (LRR) rates to better understand the role of postmastectomy radiotherapy (PMRT) in women with 0 to 3 positive lymph nodes. Clinical and pathologic factors were identified for 1019 patients with pT1 or pT2 tumors and 0 (n = 753), 1 (n = 176), 2 (n = 69), or 3 (n = 21) positive lymph nodes treated with mastectomy without PMRT during 1997 to 2002. Total LRR rates were calculated by Kaplan-Meier analysis and compared between subgroups by the log rank test. After a median follow-up of 7.47 years, the overall 10-year LRR rate was 2.7%. The only independent predictor of LRR was younger age (P = 0.004). Patients ≤40 years old had a 10-year LRR rate of 11.3 vs. 1.5% for older patients (P < 0.0001). The 10-year rate of LRR in patients with 1 to 3 positive nodes was 4.3% (94.4% had systemic therapy), which was not significantly different from the 10-year risk of contralateral breast cancer development (6.5%; P > 0.5). Compared with the 10-year LRR rate among patients with node-negative disease (2.1%), patients with 1 positive node had a similar 10-year LRR risk (3.3%; P > 0.5), and patients with 2 positive nodes had a 10-year LRR risk of 7.9% (P = 0.0003). Patients with T2 tumors with 1 to 3 positive nodes had a 10-year LRR rate of 9.7%. In patients with T1 and T2 breast cancer with 0 to 3 positive nodes, LRR rates after mastectomy are low, with the exception of patients ≤40 years old. The indications for PMRT in patients treated in the current era should be reexamined.
    Annals of Surgical Oncology 05/2010; 17(11):2899-908. · 4.12 Impact Factor
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    ABSTRACT: Axillary reverse mapping (ARM) is a novel technique to preserve upper extremity lymphatics that may reduce the incidence of lymphedema after axillary lymph node dissection. Early reports have suggested that ARM lymph nodes do not contain metastatic disease from breast cancer; however, these studies were conducted in early stage patients with low likelihood of lymph node metastasis. This study reported a phase 1 trial conducted in patients with cytologically documented axillary metastasis undergoing axillary lymph node dissection to determine the feasibility and oncologic safety of ARM. Thirty patients, 23 (77%) of whom received preoperative therapy (chemotherapy in 22 patients and hormonal therapy in 1 patient), were enrolled. Blue dye was injected in the upper inner ipsilateral arm. The presence of blue lymphatics was noted, and blue lymph nodes were sent separately for pathologic evaluation. The average time between blue dye injection and axillary exposure was 35 minutes (range, 15-60 minutes). Blue lymphatics were identified in 21 patients (70%) and blue lymph nodes in 15 patients (50%). The median number of ARM lymph nodes was 1 (range, 0-3 lymph nodes) and the median number of axillary lymph nodes was 26 (range, 6-47 lymph nodes). Axillary metastases were noted in 60% (18 of 30) of patients. Of 11 patients who had axillary metastasis and at least 1 ARM lymph node identified, 2 (18%) had metastasis to the ARM lymph node. ARM appears to be a feasible technique with which to identify upper arm lymphatics during axillary surgery. However, the high prevalence of disease involving ARM lymph nodes in this small cohort suggested that preservation of these lymphatics is not oncologically safe in women with documented axillary lymph node metastasis from breast cancer.
    Cancer 03/2010; 116(11):2543-8. · 5.20 Impact Factor
  • Isabelle Bedrosian, Chung-Yuan Hu, George J Chang
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    ABSTRACT: Despite increased demand for contralateral prophylactic mastectomy (CPM), the survival benefit of this procedure remains uncertain. We used the Surveillance, Epidemiology, and End Results database to identify 107 106 women with breast cancer who had undergone mastectomy for treatment between 1998 and 2003 and a subset of 8902 women who also underwent CPM during the same period. Associations between predictor variables and the likelihood of undergoing CPM were evaluated by use of chi(2) analyses. Risk-stratified (estrogen receptor [ER] status, stage, and age) adjusted survival analyses were performed by using Cox regression. Statistical tests were two-sided. In a univariate analysis, CPM was associated with improved disease-specific survival (hazard ratio [HR] of death = 0.63, 95% confidence interval [CI] = 0.57 to 0.69; P < .001). Risk-stratified analysis showed that this association was because of a reduction in breast cancer-specific mortality in women aged 18-49 years with stages I-II ER-negative cancer (HR of death = 0.68, 95% CI = 0.53 to 0.88; P = .004). Five year-adjusted breast cancer survival for this group was improved with CPM vs without (88.5% vs 83.7%, difference = 4.8%). Although rates of contralateral breast cancer among young women with stages I-II disease undergoing CPM were independent of ER status, women with ER-positive tumors in the absence of prophylactic mastectomy also had a lower overall risk for contralateral breast cancer than women with ER-negative tumors (0.46% vs 0.90%, difference = 0.44%; P < .001). CPM is associated with a small improvement in 5-year breast cancer-specific survival mainly in young women with early-stage ER-negative breast cancer. This effect is related to a higher baseline risk of contralateral breast cancer.
    CancerSpectrum Knowledge Environment 02/2010; 102(6):401-9. · 14.07 Impact Factor
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    ABSTRACT: We aimed to evaluate the feasibility of sentinel lymph node biopsy (SLNB) in multicentric/ multifocal breast cancer. In this prospective study, 23 women with multicentric/multifocal breast cancer underwent SLNB at our institution from April 2002 to February 2006. Presence of preoperative axillary metastases was confirmed by FNA. Patients underwent sub-areolar radiopharmaceutical injection +/- isosulfan blue to perform SLNB, then completion ALND. The false-negative (FN) rate of SLNB was determined based upon final pathology. Twenty women with multicentric and three with multifocal invasive carcinoma were enrolled. The SLN identification rate was 100%. The overall FN rate of SLNB was 15% (95% CI 0.0466, 0.4281). Both cases with FN SLNB had multicentric disease, pathologic stage III breast cancer and a larger tumor burden compared with the study population. SLNB using sub-areolar injection is feasible for patients with multicentric/multifocal breast cancer yet may be associated with a higher FN rate in patients with large additive tumor burden.
    The Breast Journal 10/2009; 15(6):645-8. · 1.83 Impact Factor
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    ABSTRACT: Objective: Sentinel lymph node (SLN) surgery is widely used for nodal staging in early-stage breast cancer. This study was performed to evaluate the accuracy of SLN surgery for patients undergoing neoadjuvant chemotherapy versus patients undergoing surgery first. Summary Background Data: Controversy exists regarding the timing of SLN surgery in patients planned for neoadjuvant chemotherapy. Proponents of SLN surgery after chemotherapy prefer a single surgical procedure with potential for fewer axillary dissections. Opponents cite early studies with low identification rates and high false-negative rates after chemotherapy. Methods: A total of 3746 patients with clinically node negative T1-T3 breast cancer underwent SLN surgery from 1994 to 2007. Clinicopathologic data were reviewed and comparisons made between patients receiving neoadjuvant chemotherapy and those undergoing surgery first. Results: Of the patients, 575 (15.3%) underwent SLN surgery after chemotherapy and 3171 (84.7%) underwent surgery first. Neoadjuvant patients were younger (51 vs. 57 years, P < 0.0001) and had more clinical T2-T3 tumors (87.3% vs. 18.8%, P < 0.0001) at diagnosis. SLN identification rates were 97.4% in the neoadjuvant group and 98.7% in the surgery first group (P = 0.017). False-negative rates were similar between groups (5/84 [5.9%] in neoadjuvant vs. 22/542 [4.1%] in the surgery first group, P = 0.39). Analyzed by presenting T stage, there were fewer positive SLNs in the neoadjuvant group (T1: 12.7% vs. 19.0%, P = 0.2; T2: 20.5% vs. 36.5%, P < 0.0001; T3: 30.4% vs. 51.4%, P = 0.04). Adjusting for clinical stage revealed no differences in local-regional recurrences, disease-free or overall survival between groups. Conclusions: SLN surgery after chemotherapy is as accurate for axillary staging as SLN surgery prior to chemotherapy. SLN surgery after chemotherapy results in fewer positive SLNs and decreases unnecessary axillary dissections.
    Annals of Surgery 09/2009; 250(4):558-566. · 6.33 Impact Factor
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    ABSTRACT: Controversy exists in the literature regarding the optimal site for lymphatic mapping in breast cancer. This study was designed to characterize lymphatic drainage patterns within the same patient after subareolar (SA) and peritumoral (PT) radiopharmaceutical injections and examine the impact of reader interpretation on reported drainage. In this prospective trial, 27 women with breast cancer underwent sequential preoperative SA and PT injections of 0.5 to 2.7 mCi of technetium-99 m filtered sulfur colloid 3 days or more apart. Patterns of radiopharmaceutical uptake were reviewed independently by two nuclear medicine physicians. Inter-reader agreement and injection success were assessed in conjunction with observed drainage patterns. There was near perfect inter-reader agreement observed on identification of axillary LN drainage after PT injection (P = 0.0004) and substantial agreement with SA injection (P = 0.0344). SA injection was more likely to drain to only axillary LNs, whereas PT injection appeared more likely to drain to both axillary and extra-axillary LNs, although no statistically significant differences were found. All patients with extra-axillary drainage after PT injection (n = 6 patients) had only axillary drainage after SA injection. Dual drainage was observed for six patients with PT injection and one patient with SA injection. Our findings suggest that radiopharmaceutical injected in the SA location has a high propensity to drain to axillary LNs only. After controlling for patient factors and demonstrating inter-reader agreement, the inability to demonstrate statistically significant differences in drainage based on injection site suggests that lymphatic drainage patterns may be a function of patient and tumor-specific features.
    Annals of Surgical Oncology 09/2009; 17(1):220-7. · 4.12 Impact Factor
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    ABSTRACT: The goal of the current study was to evaluate the effect of regional anesthesia using paravertebral block (PVB) on postoperative pain after breast surgery. Patients undergoing unilateral breast surgery without reconstruction were randomized to general anesthesia (GA) only or PVB with GA and pain scores assessed. Eighty patients were randomized (41 to GA and 39 to PVB with GA). Operative times were not significantly different between groups. Pain scores were lower after PVB compared to GA at 1 hour (1 vs 3, P = .006) and 3 hours (0 vs 2, P = .001) but not at later time points. The overall worst pain experienced was lower with PVB (3 vs 5, P = .02). More patients were pain-free in the PVB group at 1 hour (44% vs 17%, P = .014) and 3 hours (54% vs 17%, P = .005) postoperatively. PVB significantly decreases postoperative pain up to 3 hours after breast cancer surgery.
    American journal of surgery 06/2009; 198(5):720-5. · 2.36 Impact Factor
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    ABSTRACT: Optimal surgical management of patients with invasive lobular carcinoma (ILC) who undergo neoadjuvant chemotherapy (NAC) is unknown. We evaluated optimal margin distance and local recurrence (LR) rates for these patients. Ninety-three (30%) of 311 patients with ILC received NAC. We examined margin status, residual disease after re-excision, and clinical outcomes. Margin positivity rates after the final operative procedure were similar between the NAC and surgery-first group (P > .05). The proportion of patients, stratified by margin status, who were taken back for re-excision was not different between the 2 groups, and, similarly, there were no differences in frequency of residual disease (all P > .05). At a median follow-up of 3.1 years, 1 patient in the NAC group and 2 in the surgery-first group developed LR (P = 1.0). Patients with ILC who have undergone NAC and have margins >1 mm have a low probability of residual disease and LR.
    American journal of surgery 04/2009; 198(3):387-91. · 2.36 Impact Factor
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    ABSTRACT: Patients with invasive lobular carcinoma (ILC) experience a lower pathological complete response rate to neoadjuvant chemotherapy than patients with invasive ductal carcinoma. This study was intended to evaluate the impact of neoadjuvant chemotherapy in ILC on breast-conserving surgery (BCS) rates. Two-hundred eighty-four consecutive patients with pure ILC treated between May 1998 and September 2006 were reviewed. Surgical procedures and long-term outcomes were compared between patients receiving neoadjuvant chemotherapy and those receiving surgery first. Neoadjuvant chemotherapy was administered to 84 patients; 200 patients underwent surgery first. The mean tumor size in the neoadjuvant group (4.9 cm) was significantly larger than in patients who underwent surgery first (2.5 cm, p < 0.0001). In the neoadjuvant group, clinical complete response was seen in 10% and partial response in 59%. Overall BCS rates were 17% in the neoadjuvant group compared with 43% in the surgery-first group (p < 0.0001). When controlled for initial tumor size, there was no difference (all p > 0.05) between the groups in terms of (1) the proportion of patients who underwent an initial attempt at BCS, (2) rate of failure of BCS or (3) the proportion of patients undergoing BCS as their final procedure. With a mean follow-up of 47 months, local recurrence (LR) rates were similar between the two groups (1.2% versus 0.5%, p = 0.5). The use of neoadjuvant chemotherapy does not increase the rates of breast conservation in patients with pure ILC.
    Annals of Surgical Oncology 03/2009; 16(6):1606-11. · 4.12 Impact Factor
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    ABSTRACT: The intraoperative evaluation of axillary sentinel lymph nodes (SLNs) allows the surgeon to complete axillary dissection in 1 setting at the time of the primary breast surgery. However, to the authors' knowledge, there is no consensus regarding the optimal method for intraoperative evaluation of SLNs in breast cancer. The authors of this report prospectively compared touch imprint (TI) cytology with frozen section (FS) analysis and rapid cytokeratin immunostaining (RCI) of SLNs for the intraoperative evaluation of disease and compared the results with final pathologic examination (FP). Patients with invasive breast carcinoma who were diagnosed with lymph node-negative disease (based on preoperative clinical and sonographic evaluation with or without fine-needle aspiration of the indeterminate lymph nodes) and who subsequently were scheduled for lymphatic mapping were eligible to participate in this prospective protocol. TI and FS analysis were performed on all SLNs, and the lymph nodes were stained by the hematoxylin and eosin (H&E) method. RCI was performed using the enhanced polymer 1-step cytokeratin method. The results of TI, FS, RCI, TI plus FS, and FS plus RCI were compared with the results from FP, including 1 H&E stain and cytokeratin immunostain of the third level. One hundred patients with invasive mammary carcinoma were accrued to the study. Eighty-five tumors were the ductal type, 8 tumors were lobular, 5 tumors were mixed ductal and lobular, 1 was an adenoid cystic tumor, and 1 tumor was metaplastic carcinoma. Seventy-two tumors were staged clinically as T1N0M0, 25 tumors were staged as T2N0M0, and 3 tumors were staged as T3N0M0. Metastatic carcinoma was detected in the SLNs by 1 or more methods, including TI, FS, RCI, and FP, in 20 tumors, which included 12 macrometastases and 8 micrometastases. TI detected 8 of 12 macrometastases (67%), FS detected 12 of 12 macrometastases (100%), RCI detected 12 of 12 macrometastases (100%), and FP detected 12 of 12 macrometastases (100%). TI detected 1 of 8 micrometastases (13%), FS detected 3 of 8 micrometastases (38%), RCI detected 4 of 8 micrometastases (50%), and FP detected 6 of 8 micrometastases (75%). The sensitivities of TI, FS, RCI, TI plus FS, and FS plus RCI (with FP as the gold standard) were 50%, 72%, 78%, and 83%, respectively, and the sensitivities of the same intraoperative methods were 45%, 75%, 80%, and 85%, respectively, with detection of metastatic disease by any method as the gold standard. The specificities of the different methods (with FP as the gold standard) were 100% for TI and 97.5% for FS, RCI, TI plus FS, and FS plus RCI. The specificity of each method was 100% when the detection of metastatic disease by any method was regarded as the gold standard. Although the difference in sensitivity between FS and TI was not statistically significant (P = .08), the difference between RCI and TI bordered on significance (P = .046); however, FS analysis plus RCI was significantly superior to TI (P = .03) and produced results comparable to those of FP. The sensitivities of FS, RCI, TI plus FS, and FS plus RCI were better than the sensitivity of TI cytology of axillary SLNs. However, only the combination of FS and RCI was statistically superior to TI and generated results comparable to those of FP in SLNs. RCI can be completed within the time constraints for intraoperative use and, in conjunction with FS, can be useful for generating results closer to those generated by FP. FS analysis plus RCI have a role in the intraoperative evaluation of SLNs.
    Cancer 02/2009; 115(7):1555-62. · 5.20 Impact Factor
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    ABSTRACT: Although contralateral prophylactic mastectomy (CPM) reduced the risk of contralateral breast cancer in unilateral breast cancer patients, it was difficult to predict which patients were most likely to benefit from the procedure. The objective of this study was to identify the clinicopathologic factors that predict contralateral breast cancer and thereby inform decisions regarding performing CPM in unilateral breast cancer patients. A total of 542 unilateral breast cancer patients who underwent CPM at The University of Texas M. D. Anderson Cancer Center from January 2000 to April 2007 were included in the current study. A logistic regression analysis was used to identify clinicopathologic factors that predict contralateral breast cancer. Of the 542 patients included in this study, 25 (5%) had an occult malignancy in the contralateral breast. Eighty-two patients (15%) had moderate-risk to high-risk histologic findings identified at final pathologic evaluation of the contralateral breast. Multivariate analysis revealed that 3 independent factors predicted malignancy in the contralateral breast: an ipsilateral invasive lobular histology, an ipsilateral multicentric tumor, and a 5-year Gail risk >or=1.67%. Multivariate analysis also revealed that an age >or=50 years at the time of the initial cancer diagnosis and an additional ipsilateral moderate-risk to high-risk pathology were independent predictors of moderate-risk to high-risk histologic findings in the contralateral breast. The findings indicated that CPM may be a rational choice for breast cancer patients who have a 5-year Gail risk >or=1.67%, an additional ipsilateral moderate-risk to high-risk pathology, an ipsilateral multicentric tumor, or an ipsilateral tumor of invasive lobular histology.
    Cancer 01/2009; 115(5):962-71. · 5.20 Impact Factor
  • Journal of Surgical Research - J SURG RES. 01/2009; 151(2):295-295.
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    ABSTRACT: Cyclin E has been shown to be overexpressed in some human breast cancers, however, data to support deregulation of cyclin E as an early event in human mammary tumor development is lacking. We analyzed surgical specimens from 183 patients with breast carcinomas and evaluated cyclin E expression in areas of invasive carcinoma, adjacent carcinoma in situ (CIS), and non-neoplastic breast parenchyma. Overexpression of cyclin E was seen in one-third of invasive carcinoma samples, one-third of the CIS component and nearly half of the non-neoplastic breast epithelial cells adjacent to carcinoma (44% vs. 33%, P < or = 0.05). Nuclear labeling for cyclin E was highly concordant between areas of in invasive carcinoma, CIS and non-neoplastic breast epithelial cells from the same patient (P < 0.0001). Localization of cyclin E to the cytoplasm was seen in a small proportion of tumor samples. Our findings suggest that cyclin E deregulation is an early event in the progression from histologically benign mammary epithelial cells to invasive carcinoma and occurs through both overexpression and altered cellular localization.
    Breast Cancer Research and Treatment 12/2008; 115(3):651-9. · 4.47 Impact Factor
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    ABSTRACT: Factors including intratumoral heterogeneity and variability in tissue handling potentially hamper the application of reverse phase protein arrays (RPPA) to study of the solid tumor functional proteome. To address this, RPPA was applied to quantify protein expression and activation in 233 human breast tumors and 52 breast cancer cell lines. Eighty-two antibodies that recognize kinase and steroid signaling events and their effectors were validated for RPPA because of the importance of these proteins to breast carcinogenesis. Reproducibility in replicate lysates was excellent. Intratumoral protein expression was less variable than intertumoral expression, and prognostic biomarkers retained the ability to accurately predict patient outcomes when analyzed in different tumor sites. Although 21/82 total and phosphoproteins demonstrated time-dependent instability in breast tumors that were placed at room temperature after surgical excision for 24 hours prior to freezing, the functional proteomic 'fingerprint' was robust in most tumors until at least 24 hours before tissue freezing. Correlations between RPPA and immunohistochemistry were statistically significant for assessed proteins but RPPA demonstrated a superior dynamic range and detected, for example, an 866-fold difference in estrogen receptor alpha level across breast tumors. Protein and mRNA levels were concordant (at p 0.05) for 41.3% and 61.1% of assayed targets in breast tumors and cell lines, respectively. Several phosphorylation and cleavage products did not correlate with the corresponding transcript levels. In conclusion, the reproducibility of RPPA, the faithfulness with which proteins and the functional proteomic 'fingerprint' are preserved in different sections derived from primary breast tumors, and the surprising stability of this 'fingerprint' with increasing time to freezing all facilitate the application of RPPA to the accurate study of protein biomarkers in non-microdissected tumor specimens. The lack of correlation between several protein phosphorylation and cleavage products and the corresponding transcripts underlines the importance of study of the functional proteome in cancer.
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    ABSTRACT: To compare interobserver variations in delineating the whole breast for treatment planning using two contouring methods. Autosegmented contours were generated by a deformable image registration-based breast segmentation method (DEF-SEG) by mapping the whole breast clinical target volume (CTVwb) from a template case to a new patient case. Eight breast radiation oncologists modified the autosegmented contours as necessary to achieve a clinically appropriate CTVwb and then recontoured the same case from scratch for comparison. The times to complete each approach, as well as the interobserver variations, were analyzed. The template case was also mapped to 10 breast cancer patients with a body mass index of 19.1-35.9 kg/m(2). The three-dimensional surface-to-surface distances and volume overlapping analyses were computed to quantify contour variations. The median time to edit the DEF-SEG-generated CTVwb was 12.9 min (range, 3.4-35.9) compared with 18.6 min (range, 8.9-45.2) to contour the CTVwb from scratch (30% faster, p = 0.028). The mean surface-to-surface distance was noticeably reduced from 1.6 mm among the contours generated from scratch to 1.0 mm using the DEF-SEG method (p = 0.047). The deformed contours in 10 patients achieved 94% volume overlap before correction and required editing of 5% (range, 1-10%) of the contoured volume. Significant interobserver variations suggested a lack of consensus regarding the CTVwb, even among breast cancer specialists. Using the DEF-SEG method produced more consistent results and required less time. The DEF-SEG method can be successfully applied to patients with different body mass indexes.
    International journal of radiation oncology, biology, physics 10/2008; 73(5):1493-500. · 4.59 Impact Factor

Publication Stats

3k Citations
596.83 Total Impact Points

Institutions

  • 2003–2014
    • University of Texas MD Anderson Cancer Center
      • • Department of Surgical Oncology
      • • Department of Molecular Therapeutics
      Houston, Texas, United States
  • 1999–2012
    • University of Pennsylvania
      • Department of Surgery
      Philadelphia, Pennsylvania, United States
  • 2011
    • University of Groningen
      • Department of Surgery
      Groningen, Province of Groningen, Netherlands
  • 2010
    • Beaumont Hospital
      Dublin, Leinster, Ireland
  • 2009
    • Duke University Medical Center
      Durham, North Carolina, United States
  • 2008
    • University of Texas Southwestern Medical Center
      • Division of Surgical Oncology
      Dallas, TX, United States
  • 2006
    • Mayo Foundation for Medical Education and Research
      • Department of Surgery
      Scottsdale, AZ, United States
  • 2000
    • Hospital of the University of Pennsylvania
      • Department of Surgery
      Philadelphia, PA, United States