Lavinia P Middleton

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

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Publications (85)354.6 Total impact

  • Therese B. Bevers · Isabelle Bedrosian · Lavinia P. Middleton · Marion E. Scoggins ·
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    ABSTRACT: For years, surgical excision has been the standard of care for women with proliferative lesions such as atypical hyperplasia or lobular carcinoma in situ identified on needle biopsy because of concern of co-existing occult cancer. However, emerging evidence has suggested a more personalized approach of identifying women for whom surgical excision may be appropriate. A number of variables have been shown to be associated with an increased risk of a pathologic upgrade; this affords the opportunity for selective surgical excision. All women with these proliferative lesions, whether diagnosed on needle biopsy or surgical excision, are at increased risk of future breast cancers and derive significant risk reduction with endocrine therapy. Unless contraindicated, all women with atypical hyperplasia and lobular carcinoma in situ should be started on preventive therapy.
    Current Breast Cancer Reports 06/2015; 7(2). DOI:10.1007/s12609-015-0179-y
  • Shuang Zhang · Lei Huo · Elsa Arribas · Lavinia P Middleton ·
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    ABSTRACT: Adenomyoepitheliomas of breast are rare tumors. We report for the first time a case of an adenomyoepithelioma of the breast with associated lobular neoplasia. A 53-year-old woman had an annual screening mammogram, which identified areas of asymmetry in her left breast at 4-5-o'clock position. Resection of the masses revealed a well-circumscribed, gray-white, firm discrete nodule (0.8 × 0.4 × 0.3 cm). The tumor was composed of both adenomyoepithelial cell hyperplasia and focal atypical lobular hyperplasia. The 2 cell populations had some overlapping histologic features. Immunohistochemical analysis demonstrated a biphasic proliferation with approximately equal parts of luminal epithelial cells with clear and rounded appearance and myoepithelial cells. The myoepithelial component of the proliferation expressed myosin, p63, CK5/6, S-100, and dimly expressed E-cadherin. The epithelial component of the proliferation strongly expressed E-cadherin. In the areas of atypical lobular hyperplasia, there was distinct loss E-cadherin expression. Awareness of this association is highly important to provide these patients adequate follow-up and treatment. Copyright © 2015 Elsevier Inc. All rights reserved.
    Annals of Diagnostic Pathology 12/2014; 19(1). DOI:10.1016/j.anndiagpath.2014.11.002 · 1.12 Impact Factor
  • Laila Khazai · Lavinia P. Middleton · Nazli Goktepe · Benjamin T. Liu · Aysegul A. Sahin ·
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    ABSTRACT: Patients seeking a second opinion or continuation of care at our hospital will routinely have their pathology reviewed prior to initiating treatment. To assess the relevance of this review in patients with breast cancer, we compared original pathology reports submitted during the referral with second-review reports issued at our institution. We also assessed compliance with College of American Pathologists (CAP) requirements regarding inclusion of scientifically validated data elements (SVDE) in these pathology reports. We retrospectively studied all 1,970 breast pathology referral cases reviewed during one calendar year. The variables studied were histologic classification; tumor grade, necrosis, size, margin status, lymphatic/vascular invasion, dermal involvement, and biomarker profile (ER, PR, and Her-2). Each variable was rated as “agree,” “disagree,” “missing information,” or “not applicable.” A significant discrepancy, defined as a disagreement that affected patient care, was found in 226 cases (11.47%). Additionally, in 418 resection cases (31.6%), some CAP-checklist specific required information was missing. The most common areas of significant discrepancy were histologic category (66 cases; 33%) and biomarker reporting (50 cases; 25%). The most problematic diagnostic categories were intraductal lesions, lobular carcinoma, metaplastic carcinomas, and phyllodes tumors. Most disagreements in the biomarker-profile category were interpretive, but in 20% of discrepant cases, findings were supported by repeat immunohistochemical analysis. Our results confirm the value and utility of obtaining a second opinion to optimize patient care. Changes in diagnoses obtained after second review should be interpreted and reported in a collaborative fashion, noting the benefit of a review from second pair of experienced eyes. Our results support the use of second review to ensure inclusion of CAP-required data elements in pathology reports. J. Surg. Oncol. 2015 111:192–197.
    Journal of Surgical Oncology 09/2014; 111(2). DOI:10.1002/jso.23788 · 3.24 Impact Factor

  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S235-S236. DOI:10.1016/j.ijrobp.2014.05.836 · 4.26 Impact Factor
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    Lavinia P Middleton · Nour Sneige · Robin Coyne · Yu Shen · Wenli Dong · Peter Dempsey · Therese B Bevers ·
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    ABSTRACT: We evaluated the efficacy of using standard radiologic and histologic criteria to guide the follow-up of patients with lobular carcinoma in situ (LCIS), lobular neoplasia (LN), or atypical lobular hyperplasia (ALH). Patients with high-risk benign lesions diagnosed on biopsy were presented and reviewed in a multidisciplinary clinical management conference from 1 November 2003 through September 2011. Associations between patient characteristics and rates of upgrade were determined by univariate and multivariate logistic models, and times to diagnosis carcinoma were calculated. Of 853 cases reviewed, 124 (14.5%) were lobular neoplasms. In all, 104 patients were clinically and/or radiographically monitored. In 20 patients, who were found to have LN on core biopsy and were recommended to have immediate surgical excision, a more significant lesion was identified in 8 (40%) of the excised specimens. Factors associated with a more significant lesion on excisional biopsy included whether the lobular lesion had been targeted for biopsy and whether the extent of disease involved three or more terminal duct lobular units. Of the 104 patients radiographically and clinically monitored, the median follow-up time was 3.4 years with a range of 0.44-8.6 years. Five patients under surveillance were subsequently diagnosed with breast malignancy (three of the five at a site unrelated to the initial biopsy). Patients with incidental lobular lesions identified on percutaneous core needle biopsy have a small risk of upgrade and may not require an excisional biopsy. Clinical management of low-volume lobular lesions in a multidisciplinary setting is an efficacious alternative to surgical excision when radiologic and histologic characteristics are well-defined.
    Cancer Medicine 06/2014; 3(3). DOI:10.1002/cam4.223 · 2.50 Impact Factor
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    Lavinia P Middleton · Thomas W Feeley · Heidi W Albright · Ron Walters · Stanley H Hamilton ·
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    ABSTRACT: We have a crisis in health care delivery, originating from increasing health care costs and inconsistent quality-of-care measures. During the past several years, value-based health care delivery has gained increasing attention as an approach to control costs and improve quality. One proven way to control costs and improve the quality of health care is subspecialty pathologic review of patients with cancer before initiation of therapy. Our study examined the diagnostic error rate among patients with cancer treated at a tertiary care hospital and demonstrated the value of subspecialty pathologic review before initiation of treatment. From September 1 to September 30, 2011, all patients seeking a clinical consultation had pathology submitted to and reviewed by a pathologist with subspecialty expertise and correlated in our pathology database. A total of 2,718 patient cases were reviewed during September 2011. There was agreement between the original pathologist and our departmental subspecialty pathologist in 75% of cases. In 25% of cases, there was a discrepancy between the original pathology report and the subspecialty final pathology report; 509 changes in diagnosis were minor discrepancies (18.7%), and in 6.2% of patients (169 reports), the change in diagnosis represented a major discrepancy that potentially affected patient care. Second review of a patient's outside pathology by a subspecialist pathologist demonstrates the value of multidisciplinary cancer care in a high-volume comprehensive cancer center. The second review improves clinical outcomes by providing patients with evidence-based treatment plans for their precise pathologic diagnoses.
    Journal of Oncology Practice 04/2014; 10(4). DOI:10.1200/JOP.2013.001204

  • Cancer Research 03/2014; 73(24 Supplement):P5-14-08-P5-14-08. DOI:10.1158/0008-5472.SABCS13-P5-14-08 · 9.33 Impact Factor
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    ABSTRACT: Context.-Phlebotomy services are a common target for preanalytic improvements. Many new, quality engineering tools have recently been applied in clinical laboratories. However, data on relatively few projects have been published. This example describes a complete application of current, quality engineering tools to improve preanalytic phlebotomy services. Objectives.-To decrease the response time in the preanalytic inpatient laboratory by 25%, to reduce the number of incident reports related to preanalytic phlebotomy, and to make systematic process changes that satisfied the stakeholders. Design.-The Department of Laboratory Medicine, General Services Section, at the University of Texas MD Anderson Cancer Center (Houston) is responsible for inpatient phlebotomy in a 24-hour operation, which serves 689 inpatient beds. The study director was project director of the Division of Pathology and Laboratory Medicine's Quality Improvement Section and was assisted by 2 quality technologists and an industrial engineer from MD Anderson Office of Performance Improvement. Results.-After implementing each solution, using well-recognized, quality tools and metrics, the response time for blood collection decreased by 23%, which was close to meeting the original responsiveness goal of 25%. The response time between collection and arrival in the laboratory decreased by 8%. Applicable laboratory-related incident reports were reduced by 43%. Conclusions.-Comprehensive application of quality tools, such as statistical control charts, Pareto diagrams, value-stream maps, process failure modes and effects analyses, fishbone diagrams, solution prioritization matrices, and customer satisfaction surveys can significantly improve preset goals for inpatient phlebotomy.
    Archives of pathology & laboratory medicine 12/2013; 137(12):1753-1760. DOI:10.5858/arpa.2012-0458-OA · 2.84 Impact Factor
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    ABSTRACT: The management of benign papilloma (BP) without atypia identified on breast core needle biopsy (CNB) is controversial. In this study, we determined the upgrade rate to malignancy for BPs without atypia diagnosed on CNB and whether there are factors associated with upgrade. Through our pathology database search, we studied 80 BPs without atypia identified on CNB from 80 patients from 1997 to 2010, including 30 lesions that had undergone excision and 50 lesions that had undergone ≥ 2 years of radiologic follow-up. Associations between surgery or upgrade to malignancy and clinical, radiologic, and pathologic features were analyzed. Mass lesions, lesions sampled by ultrasound-guided CNB, and palpable lesions were associated with surgical excision. All 3 upgraded cases were mass lesions sampled by ultrasound-guided CNB. None of the lesions with radiologic follow-up only were upgraded to malignancy. The overall upgrade rate was 3.8%. None of the clinical, radiologic, or histologic features were predictive of upgrade. Because the majority of patients can be safely managed with radiologic surveillance, a selective approach for surgical excision is recommended. Our proposed criteria for excision include pathologic/radiologic discordance or sampling by ultrasound-guided CNB without vacuum assistance when the patient is symptomatic or lesion size is ≥ 1.5 cm.
    Clinical Breast Cancer 10/2013; 13(6). DOI:10.1016/j.clbc.2013.08.007 · 2.11 Impact Factor
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    ABSTRACT: To facilitate accurate detection of estrogen receptor (ER) expression in breast tumors, the American Society of Clinical Oncology/College of American Pathologists recommends that cold ischemia time be kept under 1 h. However, data to address the upper threshold of cold ischemia time are limited. Although it is our routine practice to keep cold ischemia time under 1 h for breast core biopsy specimens, this is difficult for surgical specimens because of the comprehensive intraoperative assessment performed at our institution. In this retrospective study, we compared ER immunohistochemical staining results in paired breast tumor core biopsy specimens and resection specimens with cold ischemia times ranging from 64 to 357 min in 97 patients. The staining category (≥10%, positive; 1–9%, low positive; <1%, negative) between the core biopsy and resection specimens changed for five patients (5%). The weighted Kappa statistic for ER staining category between the two specimen types was 0.86 (95% confidence interval, 0.74–0.99), indicating good concordance. The difference in the percentage of ER staining between core biopsy and resection was not significantly associated with cold ischemia time (P=0.81, Spearman correlation). Although we did not observe significant associations between the difference in ER staining in the two specimen types and cold ischemia time after placing the patients in three groups of ‘increase’, ‘decrease’ and ‘no change’ using a difference of 25% in ER staining percentage as the cutoff, a trend of decreased ER staining with cold ischemia time >2 h was detected. No statistically significant association was found between the change of ER staining and the history of neoadjuvant chemotherapy. Our findings indicate that prolonged cold ischemia time up to 4 h (97% of our cohort) in the practice setting of our institution has minimal clinical impact on ER immunohistochemical expression in breast tumors.
    Modern Pathology 08/2012; 26(1). DOI:10.1038/modpathol.2012.135 · 6.19 Impact Factor
  • Lavinia P. Middleton ·
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    ABSTRACT: Pleomorphic lobular carcinoma in situ (PLCIS) is a recently described variant of lobular carcinoma in situ. Although classic lobular carcinoma in situ (LCIS) is seen as a risk factor and non-obligate precursor for the development of invasive breast cancer, PLCIS is considered an even greater high-risk lesion. When patients are diagnosed with PLCIS on core biopsy, the recommendation is to perform an excisional biopsy of the affected area. Re-excision is not commonly recommended for patients with classic LCIS at or near a margin after breast conserving therapy, whereas excision with negative margins is recommended for patients with PLCIS. This review gives an overview of the biologic rationale for complete excision with negative margins for patients diagnosed with PLCIS, reviews historical data and clinical studies relevant to patients with PLCIS, and provides molecular rationale that supports treating patients with PLCIS more aggressively than patients with classic LCIS, and similar to intermediate-grade ductal carcinoma in situ (DCIS).
    Current Breast Cancer Reports 06/2012; 4(2). DOI:10.1007/s12609-012-0072-x
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    ABSTRACT: Axillary lymph node status is one of the most powerful prognostic indicators in patients with breast cancer and has implications for adjuvant treatment. It has been demonstrated that enhanced histologic evaluation of axillary lymph nodes, including serial sectioning of paraffin tissue blocks and immunohistochemical (IHC) staining, increases the rate of detection of occult metastases. The clinical significance of occult lymph node metastases has been the subject of debate. In the current study, the authors identified 267 patients who underwent axillary lymph node dissection (ALND) between 1987 and 1995 and were lymph node negative according to a routine pathologic evaluation, which included the complete submission of all lymph nodes and an examination of 1 hematoxylin and eosin (H&E)-stained section per paraffin block. Patients did not receive systemic chemotherapy or hormone therapy. All of the dissected lymph nodes from these patients were re-evaluated by intensified pathologic methods (serial sectioning with H&E levels plus IHC). Occult metastases were categorized by detection method and size. The clinical significance of the occult metastases was determined. Thirty-nine patients (15%) who had lymph node-negative results on routine evaluation of their ALND specimens had occult metastases identified. Eight of these patients (20%) had macrometastases >2.0 mm, 15 (40%) had micrometastases (range, >0.2 mm to ≤2 mm), and 16 (40%) had isolated tumor cells (≤0.2 mm). The presence of occult metastases and the size of metastases did not affect recurrence-free or overall survival. The presence of occult metastasis did not have clinical significance in this cohort of patients with early stage breast cancer.
    Cancer 03/2012; 118(6):1507-14. DOI:10.1002/cncr.26458 · 4.89 Impact Factor
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    R J Langsner · L P Middleton · J Sun · F Meric-Bernstam · K K Hunt · R A Drezek · T K Yu ·
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    ABSTRACT: Rapid in situ determination of surgical resection margins during breast cancer surgery would reduce patient time under anesthesia. We present preliminary data supporting the use of a fluorescent glucose analog (2-NBDG) as an optical contrast agent to differentiate freshly excised breast tissue containing cancerous cells from normal breast tissue. Multi-spectral images of 14 breast cancer specimens acquired before and after incubation with 2-NBDG demonstrated increased fluorescent signal in all of the malignant tissue due to increased 2-NBDG consumption. We demonstrate that 2-NBDG has potential as an optical contrast agent to differentiate cancerous from non-cancerous tissue.
    Biomedical Optics Express 06/2011; 2(6):1514-23. DOI:10.1364/BOE.2.001514 · 3.65 Impact Factor
  • Erinn Downs-Kelly · Diana Bell · George H Perkins · Nour Sneige · Lavinia P Middleton ·
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    ABSTRACT: The appropriate treatment for patients with pleomorphic lobular carcinoma in situ (PLCIS) is unknown. When diagnosed on core biopsy, excision is recommended; however, management of PLCIS when it involves margins has not been addressed. To evaluate the significance of PLCIS that is located close to, or at, a resection margin. We identified 26 patients with resection specimens containing PLCIS, all of whom were offered chemoprevention and radiation therapy. The margin status in these patients was subdivided as PLCIS cells at the margin without obvious truncation of lesion; PLCIS less than or equal to 1 mm from, but not involving, the margin; PLCIS 1.1 to 2 mm from the margin; and PLCIS at least 2.1 mm from the margin. Patient age ranged from 35 to 76 years (mean, 58 years), and length of follow-up ranged from 4 to 108 months (mean, 46 months). Six of the 26 patients (23%) received chemoprevention, 4 of 26 patients (15%) received radiation therapy, and 6 of 26 patients (23%) received both. The remaining 10 patients received no further therapy. Pleomorphic lobular carcinoma in situ was at the margin in 6 of the 26 cases (23%), 1 mm from the margin in 7 of 26 cases (27%), 1.1 to 2 mm from the margin in 4 of 26 cases (15%), and was at least 2.1 mm from the margin in 9 of 26 cases (35%). In 1 of the 26 patients, recurrent PLCIS was identified 18 months after initial surgery, for an overall recurrence rate of 3.8%. All other patients were clinically and radiologically free of disease at last follow-up. This is the first series, to our knowledge, that evaluates margin status in patients with PLCIS and documents recurrence. Recurrent PLCIS was identified at a rate similar to low- or intermediate-grade ductal carcinoma in situ. Therefore, known methods of local control, including surgical excision with negative margins (2 mm), may be the appropriate treatment in these patients.
    Archives of pathology & laboratory medicine 06/2011; 135(6):737-43. DOI:10.1043/2010-0204-OA.1 · 2.84 Impact Factor
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    ABSTRACT: Invasive mammary carcinoma with neuroendocrine differentiation has been controversial in terms of its definition and clinical outcome. In 2003, the World Health Organization histologic classification of tumors designated this entity as neuroendocrine carcinoma of the breast and defined mammary neuroendocrine carcinoma as expression of neuroendocrine markers in more than 50% of tumor cells. It is an uncommon neoplasm. Our recent study showed that it is a unique clinicopathologic entity and has a poor clinical outcome compared with invasive mammary carcinoma with similar pathologic stage. Other investigators have also demonstrated a different molecular profile in this type of tumor from that of invasive ductal carcinoma. It is unknown whether the current prognostic markers for invasive mammary carcinoma are also applicable for neuroendocrine carcinoma of the breast. In the current study, we reviewed the clinicopathologic features and outcome data in 74 cases of mammary neuroendocrine carcinoma from the surgical pathology files at The University of Texas, MD Anderson Cancer Center, to identify relevant prognostic markers for this tumor type. As shown previously by univariate analysis, large tumor size, high nuclear grade, and presence of regional lymph node metastasis are adverse prognostic factors for overall survival and distant recurrence-free survival. In the current study, multivariate analysis revealed that overall survival was predicted by tumor size, lymph node status, and proliferation rate as judged by Ki-67 immunohistochemistry. Only nodal status proved to be a significant independent prognostic factor for distant recurrence-free survival. Neither mitosis score nor histologic grade predicted survival in mammary neuroendocrine carcinoma. Our data suggest that routine evaluation of Ki-67 proliferation index in these unusual tumors may provide more valuable information than mitotic count alone.
    Human pathology 02/2011; 42(8):1169-77. DOI:10.1016/j.humpath.2010.11.014 · 2.77 Impact Factor
  • Selin Carkaci · Beatriz Adrada · Lavinia P. Middleton · Savitri Krishnamurthy · Wei Wei · Wei Tse Yang ·
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    ABSTRACT: PURPOSE To determine ultrasound (US) features that predict for axillary lymph node metastasis in patients with invasive lobular cancer (ILC), and to evaluate the sensitivity and specificity of US with and without fine needle aspiration biopsy (FNAB) in detecting axillary nodal metastasis in this patient population. METHOD AND MATERIALS Two blinded observers retrospectively analysed the US images of the axillary lymph nodes in 298 patients who had US examination of the breast and regional nodal basins at the time of initial staging for pure ILC and who subsequently underwent sentinel node biopsy and/or axillary nodal dissection. US features included length of the longest (L) and shortest (S) axes, L/S ratio, hilar status, cortical thickness, and cortical shape. Each of these features was cross-tabulated against the true metastatic status. Sensitivity, specificity, PPV, NPV, and accuracy were calculated. FNAB results of the axillary lymph nodes were compared with imaging findings and final surgical pathology. RESULTS Of the 298 patients (mean age 58 years), 138 (43%) had axillary lymph node metastases; of these 38 (27.5%) were micrometastases. The sensitivity, specificity, PPV, and NPV for US was 58%, 81%, 65%, and 75% respectively for all lymph nodes. 94 patients had FNAB of the ipsilateral axillary node prior to surgery; the sensitivity, specificity, PPV and NPV of US+FNAB was 79%, 97%, 98% and 71% respectively. Of the US features examined, cortical shape showed the highest sensitivity (57%) and NPV (76%), while presence of convex hilar indentation and hilar displacement showed the highest specificity (97%) and PPV (77%), Cortical echogenicity had the highest overall accuracy (72%), which was equivalent to overall US accuracy (71%). CONCLUSION US has a low sensitivity for the detection of axillary nodal (macro- and micro-) metastases in ILC patients. The addition of FNAB to US improves sensitivity, and suggests the need to explore alternate diagnostic methods for the detection of nodal metastases in ILC patients. CLINICAL RELEVANCE/APPLICATION The high specificity and PPV of US with and without FNAB in the detection of axillary nodal metastases in ILC patients is useful for obviating unnecessary sentinel lymph node biopsy.
    Radiological Society of North America 2010 Scientific Assembly and Annual Meeting; 11/2010
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    ABSTRACT: This prospective pilot study evaluates the potential of high-resolution fiber optic microscopy (HRFM) to identify lymph node metastases in breast cancer patients. 43 lymph nodes were collected from 14 consenting breast cancer patients. Proflavine dye was topically applied to lymph nodes ex vivo to allow visualization of nuclei. 242 images were collected at 105 sites with confirmed histopathologic diagnosis. Quantitative statistical features were calculated from images, assessed with one-way ANOVA, and were used to develop a classification algorithm with the goal of objectively discriminating between normal and metastatic tissue. A classification algorithm using mean image intensity and skewness achieved sensitivity of 79% (27/34) and specificity of 77% (55/71). This study demonstrates the technical feasibility and diagnostic potential of HRFM with fluorescent contrast in the ex vivo evaluation of lymph nodes from breast cancer patients.
    Biomedical Optics Express 10/2010; 1(3):911-922. DOI:10.1364/BOE.1.000911 · 3.65 Impact Factor
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    ABSTRACT: Glutathione-S-transferase-pi (GST-pi) is a detoxification enzyme expressed in breast cancer; however its involvement in chemotherapy sensitivity and prognosis is not well understood. We evaluated the expression of GSTpi and its predictive role of chemotherapy response. Breast tumor samples from 166 patients at stage I/II of the disease were immunostained for GST-pi, and the expression was 96 %. There was a trend toward improved disease-free survival with high GST-pi expression (p =.09). There was a statistically non-significant association between high GST-pi expression and improved outcome with adjuvant chemotherapy (p =.055). Further studies should evaluate the role of GST-pi expression in relation to response to different chemotherapies.
    Cancer Investigation 03/2010; 28(5):554-9. DOI:10.3109/07357900903286925 · 2.22 Impact Factor

  • Cancer Research 02/2010; 69(24 Supplement):4117-4117. DOI:10.1158/0008-5472.SABCS-09-4117 · 9.33 Impact Factor

  • Archives of pathology & laboratory medicine 02/2010; 134(2):162-3; author reply 163. DOI:10.1043/1543-2165-134.2.162.b · 2.84 Impact Factor

Publication Stats

3k Citations
354.60 Total Impact Points


  • 1998-2014
    • University of Texas MD Anderson Cancer Center
      • • Department of Pathology
      • • Division of Pathology and Laboratory Medicine
      • • Department of Surgical Oncology
      Houston, Texas, United States
  • 2010
    • Baylor College of Medicine
      Houston, Texas, United States
  • 2006
    • University of Houston
      Houston, Texas, United States
  • 2001
    • University of Texas Medical School
      • Department of Pathology & Laboratory Medicine
      Houston, TX, United States
  • 1998-2001
    • National Institutes of Health
      • Laboratory of Pathology
      Maryland, United States
  • 1998-1999
    • National Cancer Institute (USA)
      • Laboratory of Pathology
      베서스다, Maryland, United States