Biomedical subjects

Kelly K Hunt

Publications and source records attributed to Kelly K Hunt.

At least 127 records · Page 7Linked to original sources

PubMed2003

MDA-7 negatively regulates the beta-catenin and PI3K signaling pathways in breast and lung tumor cells.

mda-7 is a novel tumor suppressor with cytokine properties. Adenoviral mda-7 (Ad-mda7) induces apoptosis and cell death selectively in tumor cells. The molecular mechanisms underlying the anti-tumor activity of Ad-mda7 in breast and lung cancer lines were investigated. Microarray analyses implicated both the beta-catenin and the PI3K signaling pathways. Ad-mda7 treatment increased protein expression from tumor suppressor genes, including E-cadherin, APC, GSK-3beta, and PTEN, and decreased expression of proto-oncogenes involved in beta-catenin and PI3K signaling. Ad-mda7 caused a redistribution of cellular beta-catenin from the nucleus to the plasma membrane, resulting in reduced TCF/LEF transcriptional activity, and upregulated the E-cadherin-beta-catenin adhesion complex in a tumor cell-specific manner. Expression of the PI3K pathway members (p85 PI3K, FAK, ILK-1, Akt, and PLC-gamma) was downregulated and expression of the PI3K antagonist PTEN was increased. Consistent with this result, pharmacological inhibition of PI3K by wortmannin did not abrogate killing by Ad-mda7. Killing of breast cancer cells by Ad-mda7 required both MAPK and MEK1/2 signaling pathways, whereas these pathways were not essential for MDA-7-mediated killing in lung cancer cells. Thus, in breast and lung tumor cells MDA-7 protein expression modulates cell-cell adhesion and intracellular signaling via coordinate regulation of the beta-catenin and PI3K pathways.

Adenoviridae↗

PubMed2003

Evaluation of lymph node status in male breast cancer patients: a role for sentinel lymph node biopsy.

Sentinel lymph node (SLN) biopsy is rapidly emerging as an alternative to axillary lymph node dissection (ALND) for many female breast cancer patients. In contrast, ALND remains the standard of care for male breast cancer patients with similar tumors. We evaluated the results of SLN biopsy in male breast cancer patients with clinically negative axillae. This study included all male breast cancer patients who underwent SLN biopsy at our institution between October 1999 and 2000. All patients had negative axillae on clinical examination and sonography. All patients underwent preoperative lymphoscintigraphy followed by SLN biopsy performed using a combination of isosulfan blue dye and technetium Tc 99m sulfur colloid. Tc 99m sulfur colloid was injected at a dose of 2.5 mCi 24 h before surgery (four patients) or 0.5 mCi 2-4 h before surgery (three patients). Intraoperatively, 5 ml of 1% isosulfan blue was injected adjacent to the breast tumor or biopsy cavity prior to SLN biopsy. A gamma probe was used intraoperatively in order to localize SLNs. Any node that was blue or associated with ex vivo radioactivity counts at least 10 times higher than the axillary background counts was defined as a SLN. SLNs were assessed intraoperatively using touch preparation cytologic examination. Completion ALND was performed if nodal metastases were identified. Seven patients, 44-76 years of age, were included in the study. Preoperative lymphoscintigraphy identified SLNs in five patients. Intraoperatively, SLNs were identified in all seven patients. SLNs were identified in six patients using the gamma probe and in all seven patients using blue dye. The mean number of SLNs encountered was 2.9. Findings on touch preparation cytology correlated with findings on the final pathological analysis examination in all patients. One patient had a positive SLN, this patient had three additional positive nodes identified in his completion ALND specimen. Three patients with negative SLNs had been elected preoperatively to undergo ALND regardless of findings on SLN biopsy, no positive lymph nodes were identified in the ALND specimens from these patients. These findings compare favorably with findings reported in the literature regarding SLN biopsy in female breast cancer patients. Blue dye injection and radioisotope injection were complementary. SLN biopsy should be considered for axillary staging in male breast cancer patients with clinically negative axillae.

Adult↗

PubMed2003

Management of breast carcinoma identified intraoperatively during reduction mammaplasty.

Before reduction mammaplasty, patients should be assessed for breast cancer risk and evaluated with physical examination and mammography. Patients determined to be at increased risk should be informed of the possibility of occult breast carcinoma and the potential treatment options. Intraoperative discovery of an occult carcinoma may allow for breast conservation therapy under certain circumstances if an appropriate biopsy sample is taken from the tumor and if clear margins are obtained.

Breast Neoplasms↗

PubMed2003

Chest wall recurrence after mastectomy does not always portend a dismal outcome.

BACKGROUND: Chest wall recurrence (CWR) after mastectomy often forecasts a grim prognosis. Predictors of outcome after CWR, however, are not clear. METHODS: From 1988 to 1998, 130 patients with isolated CWRs were seen at our center. Clinicopathologic factors were studied by univariate and multivariate analyses for distant metastasis-free survival after CWR. The median post-CWR follow-up was 37 months. RESULTS: Initial nodal status was the strongest predictor of outcome by univariate analysis. Other significant factors included initial T4 disease, primary lymphovascular invasion, treatment of the primary tumor with neoadjuvant therapy or radiation, time to CWR >24 months, and treatment for CWR (surgery, radiation, or multimodality therapy). Multivariate analysis also found initial nodal status to have the greatest effect; time to CWR and use of radiation for CWR were also independent predictors. Three groups of patients were identified. Low risk was defined by initial node-negative disease, time to CWR >24 months, and radiation for CWR; intermediate risk had one or two favorable features; and high risk had none. The median distant metastasis-free survival after CWR was significantly different among these groups (P <.0001). CONCLUSIONS: Patients with CWR are a heterogeneous population. Patients with initial node-negative disease who develop CWR after 24 months have an optimistic prognosis, especially if they are treated with radiation.

Adult↗

PubMed2003

Clinicopathologic factors predicting involvement of nonsentinel axillary nodes in women with breast cancer.

BACKGROUND: It is unclear which breast cancer patients with positive sentinel lymph nodes (SLNs) require a completion axillary lymph node dissection. Our aim was to determine factors that predict involvement of nonsentinel axillary nodes (NSLNs) in patients with positive SLNs. METHODS: We reviewed the records of all patients with invasive breast cancer who underwent SLN biopsy at our institution between 1993 and August 2001. Multivariate analysis was used to identify clinicopathologic features in SLN-positive patients that predict involvement of NSLNs. RESULTS: A total of 131 patients had a positive SLN and underwent completion axillary lymph node dissection. Multivariate analysis revealed that primary tumor >2 cm (P =.009), SLN metastasis >2 mm (P =.024), and lymphovascular invasion (P =.028) were independent predictors of positive NSLNs. The number of SLNs harvested was a significant negative predictor (P =.04). In our model, based on the presence of these factors, the positive predictive value was 100% for a score of 4. CONCLUSIONS: The likelihood of positive NSLNs correlates with primary tumor size, size of the largest SLN metastasis, and presence of lymphovascular invasion. A scoring system incorporating these factors may help determine which patients would benefit from additional axillary surgery.

Adult↗

PubMed2003

The mitochondrial apoptosis-inducing factor plays a role in E2F-1-induced apoptosis in human colon cancer cells.

BACKGROUND: Overexpression of the transcription factor E2F-1 provokes apoptosis in cancer cells; the mechanism, however, is not completely understood. We sought to evaluate E2F-1 gene therapy in human colon cancer and to investigate the apoptotic pathway involved. METHODS: Adenoviral vectors were used to transfect the E2F-1 gene (Ad5E2F-1) or the control gene luciferase (Ad5Luc) into four human colon carcinoma cell lines. Apoptosis was confirmed by flow cytometry and poly (ADP-ribose) polymerase cleavage. Expression of apoptotic factors was determined with Western blot analysis. Inhibitory assays were used to determine the involvement of caspases in the apoptotic pathway. RESULTS: Overexpression of E2F-1 was evident in all cells treated with Ad5E2F-1; upregulation of Bcl-2, and activation of caspases were noted. The apoptosis-inducing factor in the cytosolic fraction was markedly upregulated after Ad5E2F-1 treatment. E2F-1 overexpression inhibited proliferation and induced significant apoptosis in all cell lines (P <.005). This apoptotic response could be only partially blocked by caspase inhibitors. CONCLUSIONS: These findings demonstrate that E2F-1 induces apoptosis and inhibits proliferation in human colon cancer cell lines. The marked upregulation of apoptosis-inducing factor and the fact that E2F-1-induced apoptosis is incompletely blocked by caspase inhibitors suggest a caspase-independent pathway of E2F-1-mediated apoptosis, reported here for the first time.

Adenoviridae↗

PubMed2003

Impact of clinicopathological factors on sensitivity of axillary ultrasonography in the detection of axillary nodal metastases in patients with breast cancer.

BACKGROUND: Ultrasonography and fine-needle aspiration (FNA) are used to evaluate the breast and regional nodes in breast cancer patients. We sought to identify factors influencing the sensitivity of ultrasonography for detection of nodal metastasis. METHODS: Patients with a clinically negative axilla who underwent axillary ultrasonography and sentinel lymph node biopsy were included. RESULTS: Of 208 patients, axillary ultrasonography was negative in 180 (86%) and suspicious or indeterminate in 28 (14%). FNA was performed in 22 patients whose findings were indeterminate or suspicious, and 3 were positive for malignancy. Final pathological examinations revealed positive nodes in 53 patients: 39 (22%) of 180 with negative ultrasonographic findings and 14 (50%) of 28 with indeterminate or suspicious ultrasonographic findings (P =.001). Excisional biopsy was more common for patients with indeterminate or suspicious findings on preoperative ultrasonography (P =.038). There were no significant differences in tumor size, histological features, size of nodal metastasis, or number of positive nodes between patients whose ultrasonography findings were negative and those whose findings were indeterminate or suspicious. CONCLUSIONS: Ultrasonographically suggested nodal metastasis is associated with the finding of nodal disease on final pathological examination. No significant clinicopathologic criteria were found to impact sensitivity of ultrasonography; however, excisional biopsy for diagnosis may be a confounding variable in subsequent axillary ultrasonography.

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↗

PubMed2002

Identification of distinct protein expression patterns in bilateral matched pair breast ductal fluid specimens from women with unilateral invasive breast carcinoma. High-throughput biomarker discovery.

BACKGROUND: Analysis of the biochemical and cellular contents of breast ductal fluid has recently gained attention as a potential noninvasive method for studying the local microenvironment associated with the development and progression of breast carcinoma. METHODS: Patients with unilateral primary invasive breast carcinoma were eligible for the current prospective pilot study. Nipple aspiration fluid (NAF) was obtained from the breast with cancer and the normal contralateral breast and subjected to two-dimensional electrophoresis. Computer-assisted image analysis was used to analyze NAF protein expression profiles. RESULTS: The number of separate protein spots detected in NAF samples ranged from 1280 to 1649. Substantial qualitative differences were identified between NAF protein expression patterns in the breast with cancer compared with the breast without cancer. Protein spots detected in the breast with cancer and not in the breast without cancer from the same patient varied from 30 to 202 different proteins. In addition, the number of protein spots detected in the breast without cancer and not in the breast with cancer of the same patient varied from 14 to 73 different proteins. Conversely, in an individual without breast carcinoma, only three protein spots were detected in the left breast but not the right breast, and only two were detected in the right breast but not the left breast. CONCLUSIONS: The breast is a unique organ in that its microenvironment can be readily accessed and evaluated by aspiration of fluid from the nipple. Breast ductal fluid contains a large number of proteins. As breasts are paired organs, comparisons of ductal fluid from a breast with cancer and the same patient's normal contralateral breast may reveal significant differences in protein expression associated with breast carcinoma. Recent advances in image analysis, automated mass spectrometry, and bioinformatics have provided the tools necessary to use ductal fluids from breast carcinoma patients for high-throughput biomarker discovery.

Biomarkers, Tumor↗

PubMed2002

Classifying local disease recurrences after breast conservation therapy based on location and histology: new primary tumors have more favorable outcomes than true local disease recurrences.

BACKGROUND: To distinguish true local recurrences (TR) from new primary tumors (NP) and to assess whether this distinction has prognostic value in patients who develop ipsilateral breast tumor recurrences (IBTR) after breast-conserving surgery and radiotherapy. METHODS: Between 1970 and 1994, 1339 patients underwent breast-conserving surgery at The University of Texas M. D. Anderson Cancer Center for ductal carcinoma in situ or invasive carcinoma. Of these patients, 139 (10.4%) had an IBTR as the first site of failure. For the 126 patients with clinical data available for retrospective review, we classified the IBTR as a TR if it was located within 3 cm of the primary tumor bed and was of the same histologic subtype. All other IBTRs were designated NP. RESULTS: Of the 126 patients, 48 (38%) patients were classified as NP and 78 (62%) as TR. Mean time to disease recurrence was 7.3 years for NP versus 5.6 years for TR (P = 0.0669). The patients with NP had improved 10-year rates of overall survival (NP 77% vs. TR 46%, P = 0.0002), cause-specific survival (NP 83% vs. TR 49%, P = 0.0001), and distant disease-free survival (NP 77% vs. TR 26%, P < 0.0001). Patients with NP more often developed contralateral breast carcinoma (10-year rate: NP 29% vs. TR 8%, P = 0.0043), but were less likely to develop a second local recurrence after salvage treatment of the first IBTR (NP 2% vs. TR 18%, P = 0.008). CONCLUSIONS: Patients with NP had significantly better survival rates than those with TR, but were more likely to develop contralateral breast carcinoma. Distinguishing new breast carcinomas from local disease recurrences may have importance in therapeutic decisions and chemoprevention strategies. This is because patients with new carcinomas had significantly lower rates of metastasis than those with local disease recurrence, but were more likely to develop contralateral breast carcinomas.

Actuarial Analysis↗

PubMed2002

Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells.

We evaluated anti-tumor activity and toxic effect of an adenoviral vector expressing the GFP/TRAIL fusion gene from the hTERT promoter (designated Ad/gTRAIL) on human breast cancer cell lines and on normal human breast cells. Treatment with Ad/gTRAIL elicited high levels of transgene expression and apoptosis in a variety of breast cancer cell lines. Furthermore, treatment with Ad/gTRAIL was effective in killing breast cancer lines resistant to doxorubicin or soluble TRAIL protein. In contrast, only minimal transgene expression and toxicity was detected in normal human primary mammary epithelial cells after treatment with this vector. An in vivo study further showed that the intralesional administration of Ad/gTRAIL effectively suppressed the growth of human tumor xenografts derived from both doxorubicin-sensitive and doxorubicin-resistant breast cancer lines. Specifically, about 50% of animals bearing doxorubicin-sensitive and doxorubicin-resistant breast cancer xenografts showed complete tumor regression and remained tumor-free for over 5 months. These results suggest that the adenovirus encoding the GFP/TRAIL gene driven by the hTERT promoter has potential application in cancer therapy.

Apoptosis Regulatory Proteins↗

PubMed2002

Age as a predictor of outcome for women with DCIS treated with breast-conserving surgery and radiation: The University of Texas M. D. Anderson Cancer Center experience.

PURPOSE: To analyze the long-term outcome of breast conservation therapy in patients with ductal carcinoma in situ (DCIS) in a single institution and to analyze the prognostic importance, if any, of young patient age. METHODS AND MATERIALS: The hospital records of 150 patients with DCIS treated with surgical excision and radiotherapy at our institution between 1980 and 1997 were retrospectively reviewed. For most of the patients, intraoperative specimen radiographs or postoperative mammograms were available for use in assessing that an adequate surgical resection had been performed. The median patient age was 53 years (range 32-81), with 13% of patients or=40 years, p = 0.39). In all cases of local recurrence, patients underwent surgery with or without chemotherapy, and disease control was achieved. CONCLUSION: The results of this study demonstrate high rates of long-term overall survival, disease-specific survival, and local control in patients with DCIS of the breast treated conservatively with segmental mastectomy and radiotherapy. On the basis of the excellent long-term local control and 100% disease-specific survival rates, we found that patient age does not affect the outcome if the margins are clear. Continued studies in young patients treated with breast conservative therapy for DCIS are needed.

Adult↗

PubMed2002

Role for the double-stranded RNA activated protein kinase PKR in E2F-1-induced apoptosis.

The transcription factor E2F-1 induces cell cycle progression at the G1/S checkpoint, and deregulation of E2F-1 provokes apoptosis in a wide variety of malignant cells. To date only p14(ARF) and p73, a p53 homologue, have been identified as E2F-1-inducible genes capable of mediating an apoptotic response. Here we show that adenovirus-mediated E2F-1 overexpression in cancer cells induces expression and autophosphorylation of the double-stranded RNA-dependent protein kinase PKR leading to phosphorylation of its downstream target, the alpha-subunit of the eukaryotic translation initiation factor 2 (eIF-2alpha) and to apoptotic cell death. This PKR-dependent apoptosis occurs in cell lines with mutated p53 and in cell lines with mutated p53 and p73, and is significantly reduced by the chemical inhibition of PKR activation. Further, PKR(-/-) mouse embryo fibroblasts, but not PKR(+/+) mouse embryo fibroblasts, demonstrate significant resistance to E2F-1-induced apoptosis. We conclude that an important pathway of E2F-1-mediated apoptosis is dependent on PKR activation and does not require p53 or p73.

Apoptosis↗

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

Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas.

BACKGROUND: Downstaging of large soft tissue sarcomas can be accomplished by the use of neoadjuvant chemotherapy (NeoCT). The authors tested the hypothesis that radiographic response to NeoCT predicts improved local control and survival. METHODS: The authors reviewed the medical records of 65 patients with Stage II or III soft tissue sarcoma (42 extremity, 23 retroperitoneal) who were treated with doxorubicin or ifosfamide-based NeoCT from January 1991 to December 1996. Radiographic response and impact on surgical therapy were determined retrospectively by comparing imaging studies obtained before and after chemotherapy. RESULTS: The radiographic responses observed were partial response (PR; 22 patients [34%]); minor response (MR; 6 patients [9%]); stable disease (20 patients [31%]); and progressive disease (17 patients [26%]). Downstaging sufficient to decrease the scope of the operation occurred in 13% of the patients, 78% had no change, and 9% had disease progression sufficient to increase the scope of the operation. Patients having any radiographic response (PR or MR) had a higher margin-negative resection rate, a better local recurrence-free survival rate, and a better overall survival rate than did nonresponders. CONCLUSIONS: The NeoCT regimens used in this study resulted in tumor shrinkage sufficient to impact surgical therapy in a few patients. However, radiographic response predicted improved local control and overall survival rate.

Adolescent↗

PubMed2002

Locoregional treatment outcomes for inoperable anthracycline-resistant breast cancer.

PURPOSE: To assess the therapeutic outcomes and treatment-related morbidity of patients treated with radiation for inoperable breast cancer resistant to anthracycline-containing primary chemotherapy. METHODS AND MATERIALS: We analyzed the medical records of breast cancer patients treated on five consecutive institutional trials who had been designated as having inoperable locoregional disease after completion of primary chemotherapy, without evidence of distant metastases at diagnosis. The cohort for this analysis was 38 (4.4%) of 867 patients enrolled in these trials. Kaplan-Meier statistics were used for survival analysis, and prognostic factors were compared using log-rank tests. The median follow-up of surviving patients was 6.1 years. RESULTS: Thirty-two (84%) of the 38 patients were able to undergo mastectomy after radiotherapy. For the whole group, the overall survival rate at 5 years was 46%, with a distant disease-free survival rate of 32%. The 5-year survival rate for patients who were inoperable because of primary disease extent was 64% compared with 30% for those who were inoperable because of nodal disease extent (p = 0.0266). The 5-year rate of locoregional control was 73% for the surgically treated patients and 64% for the overall group. Of the 32 who underwent mastectomy, the 5-year rate of significant postoperative complications was 53%, with 4 (13%) requiring subsequent hospitalization and additional surgical revision. Preoperative radiation doses of >or=54 Gy were significantly associated with the development of complications requiring surgical treatment (70% vs. 9% for doses <54 Gy, p = 0.0257). CONCLUSION: Despite the poorer prognosis of patients with inoperable disease after primary chemotherapy, almost one-half remained alive at 5 years and one-third were free of distant disease after multidisciplinary locoregional management. These patients have high rates of locoregional recurrence after preoperative radiotherapy and mastectomy, and the morbidity associated with this approach may limit dose-escalation strategies. Alternative therapeutic strategies such as novel systemic agents, use of planned myocutaneous repair for closure, or radiation combined with radiosensitizing agents, should be considered in this class of patients.

Adult↗

PubMed2002

Tech.Sight. Gene therapy. Hurdles and hopes for cancer treatment.

Remarkable progress has been achieved in the field of gene therapy over the past decade. The initial excitement in this young field has led to the development of more than 500 gene therapy protocols approved for evaluation in clinical trials. As these clinical trials progress, many obstacles have been identified that investigators in the field will need to overcome. Among the most important areas of investigation in the field of cancer gene therapy are 1) development of novel vectors to improve gene delivery, 2) development of tumor-selective binding to improve specific tumor targeting, and 3) improvement of the therapeutic window to reduce the toxicity of gene therapy administered alone or in combination with conventional agents. The challenge is not to replace current strategies for cancer therapy with gene therapy but to incorporate gene therapy as a more rational, molecularly based approach to increase our therapeutic armamentarium.

Adenoviridae↗

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↗