Biomedical subjects

Nour Sneige

Publications and source records attributed to Nour Sneige.

At least 19 recordsLinked to original sources

PubMed2003

Locoregional recurrence after doxorubicin-based chemotherapy and postmastectomy: Implications for breast cancer patients with early-stage disease and predictors for recurrence after postmastectomy radiation.

PURPOSE: To compare rates of locoregional recurrence (LRR) after mastectomy, doxorubicin-based chemotherapy, and radiation with those of patients receiving mastectomy and doxorubicin-based chemotherapy without radiation and to determine predictors of LRR after postmastectomy radiation. METHODS: Kaplan-Meier freedom-from-LRR rates were calculated for 470 patients treated with mastectomy, doxorubicin-based chemotherapy, and postmastectomy radiation in five single-institution clinical trials. The LRR rates in these patients were compared to previously reported rates in 1031 patients treated without radiation in the same trials. RESULTS: Median follow-up was 14 years. Irradiated patients had significantly less favorable prognostic factors for LRR than did unirradiated patients. Despite this, in all subsets of node-positive patients, postmastectomy radiation led to lower rates of LRR. This included patients with T1 or T2 tumors and one to three positive nodes (10-year LRR rates of 3% vs. 13%, p = 0.003). Multivariate analysis of LRR for patients with this stage of disease revealed that no radiation, close/positive margins, gross extracapsular extension, and dissection of <10 nodes predicted for increased LRR (hazard ratios 6.25, 4.61, 3.27, and 2.66, respectively). Significant predictors of LRR for patients treated with postmastectomy radiation were higher number and >or=20% positive nodes, larger tumor size, lymphovascular space invasion, and estrogen receptor (ER)-negative disease. Recursive partitioning analysis revealed ER-negative status to be the most powerful discriminator of LRR in irradiated patients. CONCLUSIONS: Postmastectomy radiation decreases LRR for patients with breast cancer, including those with Stage II breast cancer and one to three positive lymph nodes.

Adult↗

PubMed2003

Detection of numerical aberrations of chromosomes 7 and 9 in cytologic specimens of pleural malignant mesothelioma.

BACKGROUND: Accurate diagnosis of malignant mesothelioma (MM) in effusion fluid specimens can be challenging. Previous cytogenetic studies demonstrated that chromosomal aneusomy is commonly associated with MM. The authors attempted to determine whether the detection of numerical chromosomal aberrations in the effusion fluid specimens could be a useful diagnostic adjunct in morphologically inconclusive cases for MM. METHODS: The authors analyzed 17 cytologic specimens (15 pleural fluids, 2 fine-needle aspirates) of histologically confirmed MM obtained from 16 patients using fluorescent in situ hybridization (FISH) with centromeric chromosome 7 and 9 probes. Seventeen benign pleural effusion fluid specimens containing reactive/benign mesothelial (RM) cells were used as controls. After destaining of Diff-Quik-stained smears, the slides were hybridized using a standard FISH protocol. One hundred cells/probe/case were counted manually. RESULTS: For chromosome 7, polysomy (defined as >/= 3 signals/nucleus in >10% of the cells) was present in 88% and 0% of the MM and the RM cases, respectively. Trisomy (defined as 3 signals/nucleus in > 5% of the cells) was present in 77% and 0% of the MM and the RM cases, respectively. Tetrasomy (defined as 4 signals/nucleus in > 10% of the cells) was present in 29% and 0% of the MM and the RM cases, respectively. The mean values of positive cells showing polysomy 7 and trisomy 7 were markedly different in MM and RM cases (39% vs. 4% and 31% vs. 1%, respectively). The frequency of polysomy 9 and trisomy 9 in MM and RM cases was 69% vs. 13% and 62% vs. 6%, respectively. CONCLUSIONS: These results suggest that polysomy of chromosome 7 or 9 is a common finding in MM but uncommon in RM. Therefore, in conjunction with cytomorphologic and clinical suspicion of MM, detection of numerical chromosomal aberrations of chromosome 7 using FISH with routine cytologic smears can be a valuable diagnostic adjunct.

Aged↗

PubMed2003

Total RNA yield and microarray gene expression profiles from fine-needle aspiration biopsy and core-needle biopsy samples of breast carcinoma.

BACKGROUND: Gene expression profiling should be applicable to needle biopsy samples if microarray technology is to become practically useful for clinical research or management of breast carcinoma. This study compared gene expression profiles derived from fine-needle aspiration biopsy (FNAB) and from core needle biopsy (CBX). METHODS: Total RNA was extracted from single FNAB and CBX samples. Corresponding pairs of FNAB and CBX were analyzed for similarity of gene expression profiles using cDNA microarrays that contain 30721 human sequences. A subset of genes that distinguished CBX samples from FNAB samples was evaluated in a larger group of needle biopsy samples and in a published genomic database derived from 78 sporadic breast carcinomas with known clinical outcome. RESULTS: Sixty-eight patients with newly diagnosed breast carcinoma were included in the current study. Sixty-five patients underwent FNAB (17 had both FNAB and CBX) and 3 underwent CBX only. Extracted RNA was of suitable quality for hybridization in 46 (71%) FNABs and 15 (75%) CBXs. Total RNA yield in those samples was similar for single-pass FNAB (mean = 3.6 microg and median = 2.2 microg; n = 46) and CBX (mean = 2.8 microg and median = 2.0 microg; n = 15), with 1 microg or more of total RNA in all cases. Transcriptional profiling was performed successfully in all cases when it was attempted, in a total of 50 samples (38 FNABs and 12 CBXs), including matched FNAB and CBX samples from 10 patients. There were differences in gene expression profiles in 10 matched FNAB and CBX sample pairs. Genes that were expressed differently in CBX samples, compared with FNAB samples, were recognized as being predominantly from the endothelium, fibroblasts, myofibroblasts or smooth muscle, and histiocytes. Corresponding microscopic cell counts from FNABs demonstrated means of 80% tumor cells, 15% lymphocytes, and 5% stromal cells, whereas CBXs contained 50% tumor cells, 20% lymphocytes, and 30% stromal cells. Considering that CBXs are approximately six-fold richer in nonlymphoid stromal cells than FNABs and that CBXs differentially express a set of recognized stromal genes, the authors used these biopsies to define a transcriptional profile of breast carcinoma stroma. A set of 120 genes differentially expressed in CBXs was assessed independently in a published breast carcinoma genomic database to classify breast carcinomas based on stromal gene expression. Subgroups of tumors with low or high stromal signal were identified, but there was no correlation with the development of systemic metastases within 5 years. CONCLUSIONS: Both FNAB and CBX yield a similar quality and quantity of total RNA and are suitable for cDNA microarray analyses in approximately 70-75% of single-pass samples. Transcriptional profiles from FNAB and CBX of the same tumor generally are similar and are driven by the tumor cell population. The authors concluded that each technique has relative advantages. The FNABs provide transcriptional profiles that are a purer representation of the tumor cell population, whereas transcriptional profiles from CBXs include more representation from nonlymphoid stromal elements. Selection of the preferred needle biopsy sampling technique for genomic studies of breast carcinomas should depend on whether variable stromal gene expression is desirable in the samples.

Adult↗

PubMed2003

Nipple aspirate fluid cytology in breast carcinoma.

BACKGROUND: Nipple aspirate fluid (NAF) cytology is a simple noninvasive method to study cells exfoliated into the ductal system of the breast. In the current study, the significance of cytologic findings in NAF was determined by correlating them with histopathologic findings from corresponding breast tissue. Cytologic-histologic correlations of NAF were performed in only a few studies. METHODS: Nipple aspirate fluid was collected by breast massaging and by using a breast aspiration device from 74 women with biopsy confirmed intraductal or invasive carcinoma with or without a history of preoperative neoadjuvant chemotherapy. Cytospin preparations were Pap stained. The number of epithelial cells was quantitated and foamy macrophages were semiquantitatively scored. Cytologic findings were categorized as insufficient for diagnosis (less than 10 epithelial cells), benign, mild atypia, marked atypia or suspicious, and malignant. Finally, they were correlated with tissue findings. RESULTS: Nipple aspirate fluid was obtained from 74 women, including 24 who had received preoperative neoadjuvant chemotherapy. The median age of patients was 54 years. A mean volume of 57 microL NAF and a mean of 149 epithelial cells were obtained. Foamy macrophages were present in 51 (70%) of the specimens. There was a significant correlation between the presence of epithelial cells and foamy macrophages (P < 0.001). Patients treated with chemotherapy had fewer epithelial cells in their NAF compared with patients who were not treated with chemotherapy. Thirty specimens (41%) were inadequate for diagnosis, 34 were (46%) benign, 5 (7%) were mildly atypical, 1 (1%) was markedly atypical, and 4 (5%) were malignant. Of the five cases with mildly atypical cytology, three were intraductal papilloma, one was low-grade papillary intraductal carcinoma, and one was low-grade intracystic papillary carcinoma with invasion in the corresponding tissue specimen. The single case with markedly atypical NAF cytology had extensive ductal carcinoma in situ (DCIS). Of the four cases with malignant NAF cytology, two were extensive DCIS and two had invasive carcinoma with extensive DCIS in the breast specimen. Overall, 3 (27%) of 11 cases of DCIS were detected in NAF and only 2 (4%) of 52 invasive carcinomas including the only two cases with extensive DCIS were detected in NAF. CONCLUSION: The probability of detecting malignant cells in NAF is dependent on the extent of DCIS and nipple involvement by DCIS. Nipple aspirate fluid is not a sensitive test for detecting invasive carcinoma of the breast. Atypical cytology in NAF is associated with papillary lesions in the underlying breast.

Adult↗

PubMed2003

Histologic localization of sentinel lymph node metastases in breast cancer.

Data from a recent study support the hypothesis that axillary lymph node metastases frequently localize near the inflow junction of the afferent lymphatic vessel. Our goal was to evaluate the microscopic location of axillary sentinel lymph node metastases in a prospective study of breast cancer patients. A total of 305 axillary sentinel lymph nodes from 213 breast cancer patients undergoing surgery at our institution were evaluated. Preoperative lymphoscintigraphy using technetium-labeled sulfur colloid and intraoperative isosulfan blue dye injection were used for identifying the sentinel lymph node. Intraoperatively, the surgeon placed a suture either at the point of entry of isosulfan blue dye or at the area with the highest radioactive counts, and this area was inked at the grossing bench before processing. Metastases were identified in 55 of the 305 lymph nodes examined. Thirty-four nodes contained metastases in both the inked half and the opposite half. Metastatic tumor was identified in the inked half alone in 18 lymph nodes. Only three nodes contained metastatic tumor in the opposite half with no tumor in the inked half (p <0.001). Similar results were found when nodes tagged at the point of blue dye entry and nodes tagged at the area with the highest radioactive counts were analyzed separately. Our findings suggest that metastatic tumor has a higher probability of being present in the region of the inflow junction of the afferent lymphatic vessel. This information may be useful in determining the optimal method for evaluating axillary sentinel lymph node specimens from breast cancer patients.

Axilla↗

PubMed2003

Lobular carcinoma in situ diagnosed by core needle biopsy: when should it be excised?

Core needle biopsy is the preferred technique for evaluating breast masses and abnormal mammographic findings. The frequency of detection of noninvasive lobular lesions by core needle biopsy is increasing. Historically, the diagnosis of lobular carcinoma in situ has been considered a risk factor for the development of invasive carcinoma, and treatment has consisted of careful clinical follow-up with or without chemopreventive therapeutic agents such as tamoxifen citrate. We retrospectively reviewed core needle biopsy material with the primary diagnoses of lobular carcinoma in situ, atypical lobular hyperplasia, and lobular neoplasia in conjunction with clinical and radiographic findings to make recommendations as to when excision may be merited. We searched our database for core needle biopsy cases with lobular carcinoma in situ, atypical lobular hyperplasia, and lobular neoplasia as the primary diagnosis. Microcalcifications had been sampled with a stereotactically guided, 11 G Mammotome biopsy device, and masses had been sampled with an ultrasound guided, 18 G core needle. Glass slides were reviewed and histological parameters assessed. Mammographic findings were reviewed, and clinical information was obtained from the medical record. When available, excisional biopsy material was reviewed. The 2337 breast core needle biopsies performed from January 1995 to December 2001 included 35 (1.5%) with classic lobular carcinoma in situ (14), lobular neoplasia (4), and atypical lobular hyperplasia (17) as the primary diagnosis. Twelve of these 35 cases (34%) had histological evidence of microcalcifications directly associated with the lobular carcinoma in situ, lobular neoplasia, atypical lobular hyperplasia. Radiologic review revealed 21 calcifications, 6 ultrasonographic masses, and 8 mammographic masses and/or architectural distortions. Excisional biopsy had been performed in 17 cases (49%). In six cases diagnosed as in situ on core needle biopsy, excisional biopsy revealed invasive carcinoma. All of these patients had radiographically detectable masses. Eleven cases had excisional biopsies that showed histology similar to that of the core needle biopsies. The most important predictor of invasive carcinoma on excision was a synchronous mass lesion. Lobular carcinoma in situ involving adenosis and lobular carcinoma in situ with pagetoid spread on core needle biopsies did not show a histologically more aggressive lesion on excision and, therefore, may not require additional surgery. Histologically identified calcifications were associated with lobular lesions 34% of the time; however, their presence inside an in situ lobular lesion did not portend worse pathology on re-excision and should not be a criterion for excision. Based on these findings, we recommend excisional biopsy of lobular carcinoma in situ, atypical lobular hyperplasia or lobular neoplasia only when it is associated with a synchronous mass lesion.

Adult↗

PubMed2003

Recurrence in autogenous myocutaneous flap reconstruction after mastectomy for primary breast cancer: US diagnosis.

PURPOSE: To assess the value of ultrasonography (US) and US-guided fine-needle aspiration biopsy (FNAB) in the detection and diagnosis of recurrent cancer in breasts reconstructed with autogenous myocutaneous flaps after mastectomy for primary breast cancer and to describe the US appearances of recurrence in the reconstructed breast. MATERIALS AND METHODS: Between July 1994 and March 2001, US of the reconstructed breast was performed in 20 women with autogenous myocutaneous flap reconstruction. US findings were correlated with clinical and mammographic findings. US-guided FNAB of 25 (64%) of the 39 recurrent cancers depicted at US was performed. RESULTS: Twenty-one (54%) of the 39 recurrent cancers depicted at US were clinically occult. Mammography performed in 12 of the 20 patients with reconstructed breasts depicted 14 (56%) of the 25 recurrent cancers that were detected at US in these patients. US-guided FNAB helped to establish a definitive diagnosis of recurrent breast carcinoma in 24 (96%) of the 25 tumor specimens sampled. CONCLUSION: US and US-guided FNAB are valuable for the assessment of both palpable and clinically occult recurrent breast cancers in autogenous myocutaneous flap breast reconstructions.

Adult↗

PubMed2003

Atypical ductal hyperplasia diagnosis by directional vacuum-assisted stereotactic biopsy of breast microcalcifications. Considerations for surgical excision.

In 824 patients who underwent directional vacuum-assisted biopsies (DVABs) of breast microcalcifications, 61 (7.4%) showed atypical ductal hyperplasia (ADH). The 42 who subsequently underwent excision were the subjects of this study. Cases were evaluated for the mammographic characteristics of the lesion, the percentage of lesion removed according to mammography, and histologic findings (including number of large ducts and/or terminal duct-lobular units involved with ADH) in DVAB specimens. Pathologic findings in the surgical specimens in the area of the biopsy site also were recorded. In the DVAB specimens, ADH was confined to an average of 1.5 large ducts or lobular units and was associated with microcalcifications in all of the patients. Surgical specimens showed ADH in 15 cases, no residual lesion in 24 cases, and ductal carcinoma in situ in 3 cases. We found that microcalcifications that contain ADH in less than 3 lobules or ducts and/or that are removed completely by DVAB do not reveal higher-risk lesions on excision; thus, removal is unnecessary. When assessing microcalcifications with ADH, clinicians should consider the percentage of microcalcifications removed by DVAB and the extent of lobular involvement to better assess the need for excision.

Adult↗

PubMed2003

Mammographic-pathologic correlation of apocrine metaplasia diagnosed using vacuum-assisted stereotactic core-needle biopsy: our 4-year experience.

OBJECTIVE: To determine whether focal apocrine metaplasia of the breast has distinctive mammographic characteristics, we evaluated apocrine metaplasia diagnosed by vacuum-assisted stereotactic core-needle biopsy and correlated mammographic imaging and histopathologic findings. MATERIALS AND METHODS: We retrospectively reviewed our institutional database for records of all vacuum-assisted stereotactic core-needle biopsies performed during a 4-year period. Five hundred thirty-eight lesions were biopsied, of which 302 (56%) were benign. Apocrine metaplasia was diagnosed in 37 lesions. In 11 of these 37 lesions, apocrine metaplasia made up more than 50% of the lesion sampled. RESULTS: On mammography, eight cases (73%) appeared as new or increasing calcifications, and three cases (27%) appeared as new or enlarging equal-density masses (0.6-1.2 cm). Calcifications were heterogeneous in five lesions (63%), amorphous in two (25%), and punctate in one (12%); one heterogeneous cluster of calcifications (12%) also contained milk of calcium. The pattern of calcification distribution was clustered in five lesions (63%), multiple clusters in two (25%), and linear in one (12%). Two masses (67%) were lobular, and one (33%) was round. Two borders (67%) were microlobulated, and one (33%) was circumscribed. CONCLUSION: Apocrine metaplasia is a benign condition commonly associated with other fibrocystic changes. Lesions composed of more than 50% focal apocrine metaplasia are relatively uncommon. A new or enlarging lobular, microlobulated mass or heterogeneous calcification cluster may represent apocrine metaplasia. Because no distinguishing mammographic features are present to require follow-up by imaging, needle biopsy is required for definitive diagnosis.

Adult↗

PubMed2003

High and differential expression of HER-2/neu extracellular domain in bilateral ductal fluids from women with unilateral invasive breast cancer.

PURPOSE: Overexpression of HER-2/neu is associated with aggressive diseaseand perhaps with increased risk of breast cancer when presentin benign breast tissue. Breast ductal fluid can be obtained from women by simple nipple aspiration and may be useful for analyzing the microenvironment of the breast. EXPERIMENTAL DESIGN: After obtaining informed consent, we prospectively compared the volume of fluid collected, protein concentration, and level of HER-2/neu expression in nipple aspiration fluid (NAF) samples from both breasts and serum samples in 65 patients with unilateral primary invasive breast cancer (median age, 54 years). HER-2/neu concentrations were determined by immunoassay, with a sensitivity of 0.1 ng/ml. RESULTS: The mean NAF volume obtained and the mean NAF protein concentration were no different in the normal versus the affected breast (62.4 versus 60.4 micro l and 140.9 versus 107.8 mg/ml, respectively). Mean serum HER-2/neu level was 4.36 ng/ml (range, 0-16.8 ng/ml), approximately 50 times less than the mean NAF HER-2/neu level from all patients and all breasts (209.2 ng/ml; range, 1.0-3480.0). NAF HER-2/neu levels were significantly correlated between breasts for each individual patient (r = 0.302; P = 0.038). HER-2/neu-overexpressing tumors produced significantly more HER-2/neu in the affected breast (653.6 ng/ml) than in the unaffected breast (101.7 ng/ml) or serum (3.46 ng/ml; P = 0.016). CONCLUSIONS: Nipple aspiration is a noninvasive method for detecting tumor-specific relevant molecular changes from ductal fluid. The presence of high HER-2/neu levels in the ductal systems of breast cancer patients may have clinical implications for monoclonal antibody directed therapy.

Adult↗

PubMed2003

Gene expression profiles obtained from fine-needle aspirations of breast cancer reliably identify routine prognostic markers and reveal large-scale molecular differences between estrogen-negative and estrogen-positive tumors.

PURPOSE: The purpose of this study was to determine whether comprehensive transcriptional profiles (TPs) can be obtained from single-passage fine-needle aspirations (FNAs) of breast cancer and to explore whether profiles capture routine clinicopathological parameters. EXPERIMENTAL DESIGN: Expression profiles were available on 38 patients with stage I-III breast cancer who underwent FNA at the time of diagnosis. [(33)P]dCTP-labeled cDNA probes were generated and hybridized to cDNA membrane microarrays that contained 30,000 human sequence clones, including 10,890 expressed sequence tags. RESULTS: The median total RNA yield from the biopsies was 2 micro g (range, 1-25 micro g). The cellular composition of each biopsy was examined and, on average, 79% of the cells were cancer cells. TP was successfully performed on all 38 of the biopsies. Unsupervised complete-linkage hierarchical clustering with all of the biopsies revealed an association between estrogen receptor (ER) status and gene expression profiles. There was a strong correlation between ER status determined by TP and measured by routine immunohistochemistry (P = 0.001). A similar strong correlation was seen with HER-2 status determined by fluorescent in situ hybridization (P = 0.0002). Using the first 18 cases as the discovery set, we established a cutoff of 2.0 and 18.0 for ER and HER-2 mRNA levels, respectively, to distinguish clinically-negative from -positive cases. We also identified 105 genes (excluding the ER gene) the expression of which correlated highly with clinical ER status. Twenty tumors were used for prospective validation. HER-2 status was correctly identified in all 20 of the cases, based on HER-2 mRNA content detected by TP. ER status was correctly identified in 19 of 20 cases. When the marker set of 105 genes was used to prospectively predict ER status, TP-based classification correctly identified 9 of 10 of the ER-positive and 7 of 10 of the ER-negative tumors. We also explored supervised cluster analysis using various functional categories of genes, and we observed a clear separation between ER-negative and ER-positive tumors when genes involved in signal transduction were used for clustering. CONCLUSIONS: These results demonstrate that comprehensive TP can be performed on FNA biopsies. TPs reliably measure conventional single-gene prognostic markers such as ER and HER-2. A complex pattern of genes (not including ER) can also be used to predict clinical ER status. These results demonstrate that needle biopsy-based diagnostic microarray tests may be developed that could capture conventional prognostic information but may also contain additional clinical information that cannot currently be measured with other methods.

Adult↗

PubMed2002

Role of ultrasound-guided fine-needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma.

BACKGROUND: Ultrasound (US) is more sensitive than physical examination alone in determining axillary lymph node involvement during preliminary staging of breast carcinoma. Due to occasional overlap of sonographic features of benign and indeterminate lymph nodes, fine-needle aspiration (FNA) of sonographically indeterminate/suspicious lymph nodes can provide a more definitive diagnosis than US alone. This study was undertaken to determine the diagnostic accuracy of US-guided FNA of indeterminate/suspicious/metastatic-appearing axillary lymph nodes during the initial staging of breast carcinoma. METHODS: The cytology of 103 cases of US-guided FNA of nonpalpable indeterminate/suspicious/metastatic-appearing lymph nodes was compared with the final histopathologic status of the entire axilla after axillary dissection. The final axillary lymph node status was categorized as either negative when all lymph nodes were negative for metastasis or positive when there was evidence of metastasis in one or more lymph nodes. The sensitivity, specificity, diagnostic accuracy, and false-negative rate of US-guided FNA of nonpalpable axillary lymph nodes in the preliminary staging process were calculated. RESULTS: In 51 of 103 cases (49.5%), the US-guided FNA and histopathology were both positive for metastasis. In 24 of 103 cases (23.3%), both were negative. The apparent false-positive FNA in 16 (15.5%) cases was explained by the complete response of the metastatic lymph nodes to neoadjuvant chemotherapy in the interval between FNA and axillary dissection. In 12 cases (11.6%), US-guided FNA was negative, but metastasis was seen in histologic sections. All cases with three or more lymph nodes with metastatic disease and 93% of those with metastatic deposit measuring more than 0.5 mm were detected by US-guided FNA. The probability of detecting lymph nodes with smaller metastatic deposit measuring less than 0.5 cm was 44%. The overall sensitivity of US-guided FNA was 86.4%, the specificity was 100%, the diagnostic accuracy was 79.0%, the positive predictive value was 100%, and the negative predictive value was 67%. CONCLUSIONS: US-guided FNA of nonpalpable indeterminate and suspicious axillary lymph nodes is a simple, minimally invasive, and reliable technique for the initial determination of axillary lymph node status in breast carcinoma. The common causes of discrepancy between the initial and final axillary lymph node status include failure to visualize all lymph nodes during US examination, small-sized metastases, and preoperative neoadjuvant chemotherapy.

Axilla↗

PubMed2002

Intraoperative touch imprint of sentinel lymph nodes in breast carcinoma patients.

BACKGROUND: Sentinel lymph node examination in patients with breast carcinoma has been gaining in popularity. Currently, there is no standard intraoperative assessment of sentinel lymph nodes. To assess the utility of an intraoperative touch imprint (TI) evaluation, the authors compared TI cytology with surface hematoxylin and eosin (H&E) histology in sentinel lymph nodes from patients with breast carcinoma. METHODS: Sixty five sentinel lymph node biopsy cases were identified. Diagnoses from TI and surface H&E histologic sections were compared. RESULTS: Touch imprint had a specificity of 100%, a negative predictive value of 88%, a sensitivity of 65%, and a false negative rate of 9% per sentinel lymph node biopsy case. Eighty three percent of the false negative TI cases were due to micrometastasis. Preoperative chemotherapy, primary tumor type, and primary tumor size did not significantly contribute to false negative events. Touch imprint identified 67% of the cases that required completion axillary dissection. CONCLUSIONS: Touch imprint is a reliable and accurate intraoperative technique, with the potential to save a significant number of patients morbidity and the cost of a second surgical procedure to remove axillary lymph nodes. The difficulty of identifying micrometastases appeared to be the major source of false negative events, a problem that is not unique to TI cytology.

Adult↗

PubMed2002

Pathologic tumor size and lymph node status predict for different rates of locoregional recurrence after mastectomy for breast cancer patients treated with neoadjuvant versus adjuvant chemotherapy.

PURPOSE: To compare the pathologic factors associated with postmastectomy locoregional recurrence (LRR) in breast cancer patients not receiving radiation who were treated with neoadjuvant chemotherapy (NEO) vs. adjuvant chemotherapy (ADJ). METHODS AND MATERIALS: We retrospectively analyzed the rates of LRR of subsets of women treated in prospective trials who underwent mastectomy and received chemotherapy but not radiation. These trials were designed to answer chemotherapy questions. There were 150 patients in the NEO group and 1031 patients in the ADJ group. In the NEO group, 55% had clinical Stage IIIA or higher vs. 9% in the ADJ group (p <0.001, chi-square test). RESULTS: Despite the more advanced clinical stage in the NEO group, the pathologic size of the primary tumor and the number of positive lymph nodes (+LNs) were significantly less in the NEO group than in the ADJ group (p <0.001 for both comparisons). However, the 5-year actuarial LRR rate was 27% for the NEO group vs. 15% for the ADJ group (p = 0.001, log-rank). The 5-year risk for LRR was higher in the NEO patients for all pathologic tumor sizes: 0-2 cm (18% vs. 8%, p = 0.011), 2.1-5 cm (36% vs. 15%, p <0.001), and >5 cm (46% vs. 28%, p = 0.028). The risk of LRR by the number of +LNs was similar in the NEO and ADJ groups, except for the subset of patients with > or =4 +LNs (53% vs. 23%, p <0.001). The rates of LRR in the patients with primary tumors measuring < or =2.0 cm and 1-3 +LNs were similar in both groups. However, for the patients with a pathologic tumor size of 2.1-5.0 cm and 1-3 +LNs, the LRR was higher in the NEO group than in the ADJ group (30% vs. 15%, p = 0.016). Most failures in this NEO subgroup had clinical Stage III disease. In a subset of NEO and ADJ patients matched for clinical stage, no significant differences were found in the rates of LRR according to primary tumor size and number of +LNs when these variables were analyzed independently. Again, however, differences were found in the subgroup of patients with tumors pathologically measuring 2.1-5.0 cm with 1-3 +LNs (32% NEO vs. 8% ADJ, p = 0.030). CONCLUSION: The rates of postmastectomy LRR for any pathologic tumor size are higher for patients treated with initial chemotherapy than for patients treated with initial surgery. Radiotherapy should be offered to all patients with > or =4 +LNs, tumor size >5 cm, or clinical Stage IIIA or greater disease, regardless of whether they receive neoadjuvant or postoperative chemotherapy. The information assessing LRR rates in patients with clinical Stage II disease who receive neoadjuvant chemotherapy, particularly if 1-3 lymph nodes remain pathologically involved, is insufficient to determine whether these patients should receive radiotherapy.

Adult↗

PubMed2002

Endoscopic ultrasound-guided fine-needle aspiration in 179 cases: the M. D. Anderson Cancer Center experience.

BACKGROUND: Recently, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as a diagnostic adjunct for small pancreatic lesions and abdominal and mediastinal lymph node diseases. DESIGN: During a 21-month period, we performed 179 EUS-FNAs in 166 consecutive patients; these data are the subject of this study. An average of 2.6 needle passes were obtained and aspiration was performed most commonly in the pancreas (162 cases, 91%). The FNA smears were reviewed using six diagnostic categories (negative for malignancy/nondiagnostic [NND], atypia, suspicious for malignancy, benign tumor/cyst, neuroendocrine neoplasm [NEN], and carcinoma). The review diagnosis was correlated with the histologic diagnosis made on resection or surgical biopsy specimens in 70 cases. Up to 17 months of clinical follow-up were sought for the cases with a negative or inconclusive FNA diagnosis and no diagnostic tissue confirmation (81 cases). RESULTS: The review FNA diagnoses were as follows: NND (49 cases), atypia (17 cases), suspicious for malignancy (12 cases), benign tumor/cyst excluding NEN (10 cases), NEN (6 cases), carcinoma (85 cases). Follow-up methods included resection (49 cases), surgical biopsy (21 cases), repeat FNA or brushing cytology (28 cases), and clinical follow-up only (81 cases). Of the 49 NND cases, 23 (47%) had positive follow-up results (i.e., false-negative diagnosis) that were confirmed by tissue diagnosis (resection/surgical biopsy in 11 cases [48%] and repeat FNA/brushing in 12 cases [52%]). These included pancreatic/ampullary adenocarcinoma in 20 cases, esophageal squamous carcinoma in 1 case, and NEN in 2 cases. Follow-up also revealed carcinoma in all 12 suspicious cases and 13 pancreatic adenocarcinomas and 1 microcystic adenoma in 14 of the 17 atypical cases. Overall, repeat computed tomography (CT)-guided FNA samples yielded a definite diagnosis in four atypical and seven NND cases, whereas EUS-FNA results provided a definite diagnosis in three cases in which CT-guided FNA failed and in two cases in which ampullary biopsy failed. No false-positive cases were identified. The false-negative rate due to inadequate sampling was 13.2%. Sensitivity (including cases with inadequate cellularity and nondiagnostic aspirates) was 81.7% and specificity was 100%. None of the factors evaluated (lesion characteristics, aspiration site, and tumor type) significantly influenced diagnostic results. CONCLUSION: EUS-FNA is a valuable diagnostic and staging tool with high specificity and sensitivity. Negative or nondiagnostic cases on EUS-FNA require further diagnostic work for a definitive diagnosis when clinical or radiographic findings do not correlate with the FNA results.

Abdominal Neoplasms↗

PubMed2002

Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer.

PURPOSE: To evaluate the safety and efficacy of weekly docetaxel plus trastuzumab in women with HER-2-overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels. PATIENTS AND METHODS: Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuzumab as first- or second-line therapy. Both docetaxel 35 mg/m(2)/wk and trastuzumab 2 mg/kg/wk were delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. A loading dose of trastuzumab 4 mg/kg was administered 1 day before the start of the first cycle. RESULTS: The median delivered dose-intensity of docetaxel was 24 mg/m(2)/wk (range, 18 to 27 mg/m(2)/wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval [CI], 44% to 80%). The ORR in patients whose tumors were HER-2-positive by fluorescence in situ hybridization was 67% (16 of 24 patients; 95% CI, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% CI, 53% to 92%), compared with 33% (95% CI, 7% to 70%) in patients with low HER-2 ECD levels (P =.04). Variations in HER-2 ECD concentrations during treatment correlated with response to treatment. Median time to progression was 9 months. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and excessive tearing became more common with repetitive dosing. CONCLUSION: Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2-overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy.

Adult↗

PubMed2002

Interventional breast sonography.

This review article covers the basic applications of and latest developments in interventional breast sonography (US). For breast masses, US has become the standard for guiding needle biopsy, whether a fine needle or a core biopsy needle is used. US has also become the preferred method for guiding insertion of various localization devices for nonpalpable masses, and US's intraoperative use for this purpose is expanding. Recently, US has been used to monitor the placement of percutaneous ablation devices, such as radiofrequency ablation needle-electrodes, into breast masses, including carcinomas. US is not indicated for the routine evaluation of microcalcifications. However, on occasion, clusters of microcalcifications without a mass can be visualized on sonograms with sufficient clarity to undertake a US-guided core biopsy if stereotactically guided biopsy cannot be performed for technical reasons.

Biopsy, Needle↗

PubMed2002

Molecular and biologic markers of premalignant lesions of human breast.

There is currently great interest in the detection and characterization of putative precursor breast cancer lesions because of the possibility of chemoprevention. Knowledge of the biologic features of premalignant lesions, although limited, is rapidly evolving. Premalignant breast lesions have been examined for the presence of genetic alterations and for the expression of biomarkers such as the estrogen receptor (ER), Ki67, p53, and HER2/neu. Data obtained from genetic studies of precursor breast lesions clearly support the contention that genetic alterations begin quite early in selected subsets of histologically benign lesions. Although the results of biomarker expression profiles have been contradictory, most studies agree that precursor lesions significantly overexpress ER and that progressive alterations in ER expression accompany the transition of normal cells to hyperplastic lesions and carcinoma in situ. So far, the collected evidence indicates that precursor lesions in the breast demonstrate biomarker expression profiles and genetic abnormalities that are distinct from those of terminal ductal lobular units but share some of these features with invasive tumors. Future research in this field is urgently needed to identify specific biomarkers of prognostic and predictive value, which can help not only in the selection of patients for chemopreventive therapy but in monitoring the progression of high-risk lesions.

Biomarkers, Tumor↗