Biomedical subjects

Lee K Tan

Publications and source records attributed to Lee K Tan.

14 recordsLinked to original sources

PubMed2005

The results of frozen section, touch preparation, and cytological smear are comparable for intraoperative examination of sentinel lymph nodes: a study in 133 breast cancer patients.

BACKGROUND: The goal of intraoperative sentinel lymph node (SLN) examination is to avoid reoperation for a positive SLN, but the ideal method of intraoperative SLN examination remains unclear, and published results vary widely. METHODS: We evaluated the sensitivity of intraoperative frozen section (FS), touch preparation (TP), and cytological smear (CS) in 305 SLNs from 133 breast cancer patients. Each SLN was received fresh and cut into 2- to 3-mm slices; TP and CS from each cut surface and an FS of the entire SLN were obtained. Postoperative evaluation of the SLN consisted of 1 hematoxylin and eosin-stained section and of one hematoxylin and eosin-stained and one immunohistochemically stained section for cytokeratin from each of two levels 50 microm apart. Tumor cells found by any method, including immunohistochemistry, identified a positive SLN. Three pathologists blinded to the final SLN diagnosis reviewed all TP, CS, and FS; the consensus diagnosis (concordance of two or more) was used for the study. RESULTS: FS, TP, and CS had comparable sensitivities (59%, 57%, and 59%, respectively). Each method was more sensitive in detecting macrometastases (>2 mm; 96%, 93%, and 93%, respectively) than micrometastases (< or =2 mm; 27%, 27%, and 30%, respectively). The combination of methods only marginally improved the intraoperative sensitivity. TP and CS were each responsible for a single false-positive result. CONCLUSIONS: FS, TP, and CS are comparable for the intraoperative detection of SLN metastases, and each method is substantially better at detecting micrometastases than micrometastases. The combination of two or more techniques only marginally improves the sensitivity over that achieved by a single method.

Adult↗

PubMed2005

A phase II trial of imatinib mesylate monotherapy in patients with metastatic breast cancer.

BACKGROUND: Imatinib mesylate is a potent inhibitor of Abl, KIT, and PDGFR tyrosine kinases. Breast cancer has variable expression of KIT and PDGFR therefore we conducted a phase II trial to evaluate the safety and efficacy of imatinib in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients had measurable and progressive MBC, with no limits on prior chemo- or hormonal therapy. Imatinib was initially administered at a dose of 400 mg orally twice a day with provisions for dose reductions based on toxicities. The primary endpoint was clinical benefit based on RECIST criteria. Tumor specimens were tested for expression of KIT and PDGFR tyrosine kinases. RESULTS: Sixteen patients were enrolled and treated. Median age was 55 years (range: 35-73); median number of prior chemotherapy regimens for MBC was 4 (range 1-8). The main non-hematologic toxicities were (Grades 1/2; Grade 3): fatigue (56%; 6%), edema (38%; 19%), nausea (31%; 19%), vomiting (38%; 0%), anorexia (38%; 0%), diarrhea (19%; 6%), and rash (25%; 6%). Grade 3/4 hematologic and biochemical abnormalities were minimal. There was no evidence of clinical benefit. The median duration of therapy on trial was 28 days (range 2-71). Of the 13 testable cases: 1 was KIT positive and 4 were PDGFR positive. CONCLUSION: Imatinib therapy at doses of 800 mg/day was associated with significant toxicity in patients with heavily pre-treated MBC. Our results do not indicate activity for imatinib monotherapy in these unselected patients.

Adult↗

PubMed2005

Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary.

Metastatic breast carcinoma to the ovary is sometimes difficult to differentiate from primary ovarian carcinoma. This problem is often encountered in breast carcinoma patients who develop adnexal masses. ER and PR can be positive in a high percentage of breast and ovarian carcinomas, and therefore cannot be used in the differential diagnosis of these entities. WT1 and CA125 have been identified as possible markers for ovarian cancer. However, no studies have been done that specifically compare the immunophenotype of breast carcinoma metastatic to ovary with that of primary ovarian cancer. Thirty-nine cases of metastatic breast carcinoma to the ovary, 36 primary breast carcinomas, and 42 primary ovarian carcinomas were examined immunohistochemically for the expression of WT1, CA125, carcinoembryonic antigen, MUC2, MUC1, and GCDFP. The percentage of cells stained and the intensity of staining were recorded. Thirty-two ovarian carcinomas (76%) were positive for WT1, including 31 of 33 (94%) serous carcinomas. Most of them had strong and diffuse staining. None of the breast cancers either primary or metastatic to the ovary expressed WT1. Thirty-eight (90%) ovarian carcinomas were positive for CA125, most of them with strong and diffuse staining. Most breast carcinomas were negative for CA125, with only 6 (16%) of the primary ones and 5 (12%) of the metastatic showing weak and focal positivity. All ovarian carcinomas were negative for GCDFP. Five primary breast cancers (14%) and 17 (43%) metastatic to the ovary were positive for GCDFP. Nine (21%) ovarian carcinomas, 8 (22%) primary breast carcinomas, and 13 (33%) metastatic to the ovary were positive for carcinoembryonic antigen. Almost all tumors examined were positive for MUC1 (100% ovarian carcinomas, 100% primary breast carcinomas, and 95% metastatic breast carcinomas to ovary). MUC2 was positive in 10 (24%) ovarian carcinomas, 3 (8%) primary breast cancers, and 12 (30%) metastases to the ovary. The presence of immunoreactivity for WT1 and CA125 in a carcinoma involving ovary strongly favors a primary lesion. Most ovarian carcinomas are positive for both markers, whereas the majority of metastatic breast carcinomas to the ovary are negative. GCDFP can be complementary in this differential diagnosis.

Antigens↗

PubMed2005

Correlation of HER-2 status with estrogen and progesterone receptors and histologic features in 3,655 invasive breast carcinomas.

We studied the inverse relationship between HER-2 and estrogen (ER) and progesterone (PR) receptors using HER-2 testing and correlated HER-2 status with histologic features in 3,655 unselected invasive breast carcinomas. Immunohistochemical analysis for ER, PR, and HER-2 and fluorescence in situ hybridization for HER-2 were performed. ER and PR expression were decreased significantly in HER-2+ tumors compared with HER-2- tumors (ER, 49.1% vs 78.17%; PR, 24.3% vs 53.13%). Even among HER-2+ tumors, the rate of ER or PR expression in high-grade tumors was significantly decreased compared with intermediate-grade tumors. HER-2 was positive in 10.87% of grade 2 and 27.84% of grade 3 ductal carcinomas and negative in all grade 1 ductal carcinomas. HER-2 overexpression or amplification essentially was limited to grades 2 and 3 ductal carcinomas and correlated inversely with ER or PR expression. Although ER or PR expression is decreased in HER-2+ tumors, a substantial proportion of them still express ER or PR.

Breast Neoplasms↗

PubMed2004

A tool for predicting breast carcinoma mortality in women who do not receive adjuvant therapy.

BACKGROUND: Among the several proposed risk classification schemes for predicting survival in women with breast carcinoma, one of the most commonly used is the Nottingham Prognostic Index (NPI). The goal of the current study was to use a continuous prognostic model (similar to those that have already been demonstrated to possess greater predictive accuracy than risk group-based models in other malignancies) to predict breast carcinoma mortality more accurately compared with the NPI. METHODS: A total of 519 women who had been treated with mastectomy and axillary lymph node dissection at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1976 and 1979 met the following requirements for study inclusion: confirmation of the presence of invasive mammary carcinoma, no receipt of neoadjuvant or adjuvant systemic therapy, no previous history of malignancy, and negative lymph node status as assessed on routine histopathologic examination. Paraffin blocks were available for 368 of the 519 eligible patients. All available axillary lymph node tissue blocks were subjected to enhanced pathologic analysis. The competing-risk method was used to predict disease-specific death, and the accuracy of the novel prognostic model that emerged from this process was evaluated using the concordance index. Jackknife and 10-fold cross-validation predictions yielded by this new model were compared with predictions yielded by the NPI. RESULTS: Of the 348 women for whom complete data were available, 73 died of disease; the 15-year probability of breast carcinoma-related death was 20%. On the basis of these 348 cases, the authors developed a prognostic model that took patient age, disease multifocality, tumor size, tumor grade, lymphovascular invasion, and enhanced lymph node staining into account, and using competing-risks regression analysis, they found that this new model predicted disease-specific death more accurately compared with the NPI. CONCLUSIONS: The authors have developed a model for predicting breast carcinoma-specific death with improved accuracy. This tool should be useful in counseling patients with regard to their specific need for adjuvant therapy.

Adult↗

PubMed2004

Cytokeratin-positive cells in sentinel lymph nodes in breast cancer are not random events: experience in patients undergoing prophylactic mastectomy.

BACKGROUND: The incidence of immunohistochemistry (IHC)-detected epithelial cell displacement in sentinel lymph node (SLN) biopsy is unknown. In the current study, we address this question by examining the pattern of SLN involvement in patients undergoing prophylactic mastectomy (PM) at Memorial Sloan-Kettering Cancer Center (New York, NY). METHODS: Between January 1999 and January 2003, 5275 patients underwent SLN biopsy. Unilateral or bilateral PM with SLN biopsy was performed in 143 (2.7%) patients, representing 163 PM cases. RESULTS: Occult carcinoma was identified in 13 of 163 (8.0%) PM specimens. Two patients with occult invasive carcinoma had positive SLNs (hematoxylin and eosin). In the remaining 150 PM cases without occult carcinoma (130 patients), 89% underwent IHC analysis of the SLNs. Of these 130 patients, 43 (33%) had one or more prior biopsies in their "cancer-free" breast, a median of 43 days (range, 3-314 days) before PM. A total of 310 SLNs were examined by IHC (mean, 2.3 lymph nodes per PM case). Only 1 of 130 (0.8%) patients without occult carcinoma had an IHC-positive SLN. This patient had Stage IIIC carcinoma of the contralateral breast. IHC-positive SLNs were not identified in any of the 43 patients with a history of prior biopsy. Therefore, only 1 IHC-positive SLN was detected in 310 (0.3%) lymph nodes examined. CONCLUSIONS: IHC-positive cells in SLNs are rare in the absence of cancer and are not the result of previous breast instrumentation. Although the prognostic significance of IHC-positive cells remains controversial, the current study suggests that they are not random events.

Adult↗

PubMed2004

Immunohistochemically detected tumor cells in the sentinel lymph nodes of patients with breast carcinoma: biologic metastasis or procedural artifact?

BACKGROUND: Sentinel lymph node (SLN) biopsy is a new standard of care for patients with breast carcinoma, and allows enhanced pathologic analysis with serial sections and immunohistochemical (IHC) staining for cytokeratins to be performed on a routine basis. However, the significance of SLN micrometastases detected only by IHC is uncertain. Are these tumor cells truly markers of metastatic potential, or simply evidence of passive displacement by preoperative instrumentation of the tumor site? Here we evaluate whether the pattern of SLN metastasis in breast carcinoma is related to the degree of manipulation at biopsy before surgery, independently of other known predictors. METHODS: Among 4016 consecutive eligible patients with breast carcinoma registered in a prospective SLN database at Memorial Sloan Kettering Cancer Center, we noted patient/tumor characteristics, pathologic status of the SLN (negative, positive by hematoxylin and eosin [H&E], or positive only on IHC), and method of previous biopsy (none, fine-needle aspiration biopsy [FNAB], core needle biopsy, or surgical biopsy). RESULTS: Multivariate analysis showed that the likelihood of an H&E-positive SLN was significantly associated with lymphovascular invasion, tumor size, tumor type, and tumor location, but not with the method of biopsy. In contrast, the likelihood of finding an SLN positive only on IHC was unassociated with any of the four variables above, but was significantly associated with the method of biopsy. After no previous biopsy, FNAB, core needle biopsy, or surgical biopsy, IHC-positive SLN were present in 1.2%, 3.0%, 3.8%, and 4.6% of patients, respectively (P = 0.002). CONCLUSIONS: These data suggest that the frequency of IHC-positive SLN in patients with breast carcinoma 1) is unrelated to conventional predictors of lymph node positivity, 2) is increased after instrumentation of the tumor site, and 3) is increased approximately proportionate to the degree of manipulation. A proportion of IHC-positive SLN were present before biopsy and therefore less likely to be artifactual.

Adult↗

PubMed2004

Redefining prognosis in node-negative breast cancer: can sentinel lymph node biopsy raise the threshold for systemic adjuvant therapy?

Sentinel lymph node (SLN) biopsy is a new standard of care for axillary node staging in breast cancer, which for the first time allows enhanced pathologic analysis on a routine basis. Although a number of retrospective studies, including our own series with 20-year follow-up, suggest that axillary nodal micrometastases found in this manner are prognostically significant, prospective trials now under way promise a definitive answer to this controversial subject. Enhanced pathology using serial sections and immunohistochemical staining identifies a high-risk minority of conventionally node-negative patients who are converted to node-positive and thereby become candidates for systemic adjuvant chemotherapy. The developmental phase of SLN biopsy, now drawing to a close, has focused on the identification of this node-positive group. Enhanced pathology also identifies a majority of patients who are truly node-negative and whose expectation of long-term survival exceeds that of historic norms for node-negative breast cancer. The next era of SLN biopsy should focus on the characterization of this group. SLN biopsy in breast cancer has already extended the historic trend toward surgical conservatism. By defining more precisely a low-risk cohort of patients, SLN biopsy has the potential to initiate a trend toward medical conservatism as well.

Axilla↗

PubMed2003

Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells.

Breast cancer is a genetically and clinically heterogeneous disease, and the contributions of different target cells and different oncogenic mutations to this heterogeneity are not well understood. Here we report that mammary tumors induced by components of the Wnt signaling pathway contain heterogeneous cell types and express early developmental markers, in contrast to tumors induced by other signaling elements. Expression of the Wnt-1 protooncogene in mammary glands of transgenic mice expands a population of epithelial cells expressing progenitor cell markers, keratin 6 and Sca-1; subsequent tumors express these markers and contain luminal epithelial and myoepithelial tumor cells that share a secondary mutation, loss of Pten, implying that they arose from a common progenitor. Mammary tumors arising in transgenic mice expressing beta-catenin and c-Myc, downstream components of the canonical Wnt signaling pathway, also contain a significant proportion of myoepithelial cells and cells expressing keratin 6. Progenitor cell markers and myoepithelial cells, however, are lacking in mammary tumors from transgenic mice expressing Neu, H-Ras, or polyoma middle T antigen. These results suggest that mammary stem cells and/or progenitors to mammary luminal epithelial and myoepithelial cells may be the targets for oncogenesis by Wnt-1 signaling elements. Thus, the developmental heterogeneity of different breast cancers is in part a consequence of differential effects of oncogenes on distinct cell types in the breast.

Animals↗

PubMed2003

The accuracy of sentinel lymph node biopsy in multicentric and multifocal invasive breast cancers.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has proved to be an accurate alternative to complete axillary lymph node dissection (ALND) in clinically node-negative breast cancer patients. Multicentric (MC) and multifocal (MF) invasive breast cancers are considered to be relative contraindications to SLNB. We examine the accuracy of SLNB in patients with MC and MF invasive breast cancers. STUDY DESIGN: From September 1996 to August 2001, a total of 3,501 patients with clinically node-negative breast cancer underwent SLNB using both blue dye and radioisotope at our institution. A total of 70 patients had MC or MF invasive breast cancer, a successful SLNB, and mastectomy for local control. All had >/=10 axillary nodes excised (including the SLN) in a planned ALND. Exclusion criteria included MC and MF in situ carcinoma; breast conservation; previous breast irradiation, ALND, or SLNB; recurrent breast cancer; neoadjuvant chemotherapy; or ALND based solely on SLNB pathologic examination. RESULTS; The incidence of axillary metastases was 54% (38 of 70). SLNB accuracy was 96% (67 of 70), sensitivity 92% (35 of 38), and false-negative rate 8% (3 of 38). All patients with an inaccurate SLNB had a dominant invasive tumor >5 cm and one patient had palpable axillary disease intraoperatively. The SLN was the only site of axillary metastasis in 37% (14 of 38). Results were compared with those of published SLNB validation studies, most of which reflect experience with single-site invasive breast cancers. No statistically significant difference was noted for accuracy, sensitivity, or false-negative rate. CONCLUSIONS: SLNB accuracy in MC and MF disease is comparable with that of published validation studies. MC and MF patients with a dominant T3 tumor (>5 cm) or axillary disease palpable intraoperatively should have a concurrent formal ALND. Our retrospective data suggest SLNB may be used as a reliable alternative to conventional ALND in selected patients with MC or MF disease. Further studies in this patient population are warranted.

Adult↗

PubMed2003

A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy.

BACKGROUND: The standard of care for breast cancer patients with sentinel lymph node (SLN) metastases includes complete axillary lymph node dissection (ALND). However, many question the need for complete ALND in every patient with detectable SLN metastases, particularly those perceived to have a low risk of non-SLN metastases. Accurate estimates of the likelihood of additional disease in the axilla could assist greatly in decision-making regarding further treatment. METHODS: Pathological features of the primary tumor and SLN metastases of 702 patients who underwent complete ALND were assessed with multivariable logistic regression to predict the presence of additional disease in the non-SLNs of these patients. A nomogram was created using pathological size, tumor type and nuclear grade, lymphovascular invasion, multifocality, and estrogen-receptor status of the primary tumor; method of detection of SLN metastases; number of positive SLNs; and number of negative SLNs. The model was subsequently applied prospectively to 373 patients. RESULTS: The nomogram for the retrospective population was accurate and discriminating, with an area under the receiver operating characteristic (ROC) curve of 0.76. When applied to the prospective group, the model accurately predicted likelihood of non-SLN disease (ROC, 0.77). CONCLUSIONS: We have developed a user-friendly nomogram that uses information commonly available to the surgeon to easily and accurately calculate the likelihood of having additional, non-SLN metastases for an individual patient.

Adult↗

PubMed2003

MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer.

OBJECTIVE: The purpose of this study was to review MR imaging findings in the ipsilateral breast in women with percutaneously proven breast cancer. MATERIALS AND METHODS: Retrospective review was performed of records of 70 consecutive women with percutaneously proven unilateral breast cancer who were considered candidates for breast conservation surgery and who had preoperative MR imaging of the ipsilateral breast. MR images and medical records were reviewed. RESULTS: MR imaging identified mammographically and clinically occult cancer other than the index lesion in the ipsilateral breast in 19 women (27%), including infiltrating cancer in 11 women (16%) and ductal carcinoma in situ in eight women (11%). These additional sites of cancer were in the same quadrant as the index cancer in 14 women (20%), in a different quadrant in three women (4%), and in both the same and different quadrants in two women (3%). Additional sites of cancer were more likely in women with, rather than in those without, a family history of breast cancer (42% vs 14%, p < 0.02) and in women whose index cancer was infiltrating lobular rather than other histologies (55% vs 22%, p < 0.06). In 17 women (24%), MR imaging detected ipsilateral lesions that were benign. Changes due to prior percutaneous biopsy were infrequently observed on MR images and included a clip in 12 women (17%) and a small hematoma in two women (3%). CONCLUSION: MR imaging identified additional sites of ipsilateral cancer in 27% of women with percutaneously proven breast cancer. The yield was highest in women with a family history of breast cancer or infiltrating lobular histology in the index cancer. Change after biopsy was infrequent and did not interfere with the MR imaging interpretation.

Adult↗

PubMed2003

Ductal enhancement on MR imaging of the breast.

OBJECTIVE: The purpose of this study was to determine the prevalence and positive predictive value of ductal enhancement among MR imaging-detected breast lesions that had biopsy and to assess the histologic findings associated with ductal enhancement. MATERIALS AND METHODS: Retrospective review was performed of 427 nonpalpable, mammographically occult lesions that had MR imaging-guided needle localization and surgical biopsy. Lesions were reviewed by one radiologist who was unaware of the histologic outcomes and were classified according to a standardized lexicon. MR imaging and histologic findings of ductal enhancing lesions were reviewed. RESULTS: Ductal enhancement accounted for 88 (21%) of 427 lesions and 88 (59%) of 150 nonmass lesions. Histologic finding in these 88 lesions were ductal carcinoma in situ (DCIS) in 18 (20%); infiltrating carcinoma in five (6%), including three with DCIS; lobular carcinoma in situ (LCIS) in nine (10%); atypical ductal hyperplasia in eight (9%); and benign in 48 (55%). Among the 48 benign lesions, the dominant histologic findings were fibrocystic change (n = 16); ductal hyperplasia (n = 8); fibrosis (n = 8); postbiopsy change (n = 5); benign breast tissue (n = 3); sclerosing adenosis (n = 2); and single cases of fibroadenoma, fibroadenomatoid change, lymph node, mastitis, papilloma, and radial scar. Factors associated with a trend toward a higher frequency of carcinoma included clumped enhancement (p = 0.05) and synchronous ipsilateral cancer (p = 0.07). CONCLUSION: Ductal enhancement accounted for 21% of MR imaging-detected lesions that had biopsy and had a positive predictive value of 26%. Differential diagnosis of ductal enhancement includes carcinoma (usually DCIS); atypical ductal hyperplasia; LCIS; and benign findings such as fibrocystic change, ductal hyperplasia, and fibrosis.

Adult↗

PubMed2003

Fast MRI-guided vacuum-assisted breast biopsy: initial experience.

OBJECTIVE: The purpose of this study was to evaluate a new method for performing MRI-guided vacuum-assisted breast biopsy in a study of lesions that had subsequent surgical excision. SUBJECTS AND METHODS. Twenty women scheduled for MRI-guided needle localization and surgical biopsy were prospectively entered in the study. MRI-guided biopsy was performed with a vacuum-assisted probe, followed by placement of a localizing clip, and then needle localization for surgical excision. Vacuum-assisted biopsy and surgical histology were correlated. RESULTS: Vacuum-assisted biopsy was successfully performed in 19 (95%) of the 20 women. The median size of 27 MRI-detected lesions that had biopsy was 1.0 cm (range, 0.4-6.4 cm). Cancer was present in eight (30%) of 27 lesions and in six (32%) of 19 women; among these eight cancers, five were infiltrating and three were ductal carcinoma in situ (DCIS). Among these 27 lesions, histology was benign at vacuum-assisted biopsy and at surgery in 19 (70%), cancer at vacuum-assisted biopsy in six (22%), atypical ductal hyperplasia at vacuum-assisted biopsy and DCIS at surgery in one (4%), and benign at vacuum-assisted biopsy with surgery showing microscopic DCIS that was occult at MRI in one (4%). The median time to perform vacuum-assisted biopsy of a single lesion was 35 min (mean, 35 min; range, 24-48 min). Placement of a localizing clip, attempted in 26 lesions, was successful in 25 (96%) of 26, and the clip was retrieved on specimen radiography in 22 (96%) of 23. One complication occurred: a hematoma that resolved with compression. CONCLUSION: MRI-guided vacuum-assisted biopsy is a fast, safe, and accurate alternative to surgical biopsy for breast lesions detected on MRI.

Adult↗