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Kelly K Hunt

Publications and source records attributed to Kelly K Hunt.

At least 55 records · Page 3Linked to original sources
PubMed2005

Incidence of anaphylactoid reactions to isosulfan blue dye during breast carcinoma lymphatic mapping in patients treated with preoperative prophylaxis: results of a surgical prospective clinical practice protocol.

BACKGROUND: Severe anaphylactoid reactions to isosulfan blue dye requiring resuscitation are reported to occur in 1.1% of patients with breast carcinoma undergoing sentinel lymphadenectomy. In December 2001, the authors began administering a prophylactic regimen before dye injection to determine whether prophylaxis reduced the incidence of life-threatening reactions. METHODS: All patients were mapped with technetium-99m-labeled sulfur colloid. Those also receiving isosulfan blue dye were administered a glucocorticoid, diphenhydramine, and famotidine intravenously just before or at induction of anesthesia. Adverse reactions at the time of surgery were analyzed. RESULTS: Between December 2001 and July 2003, 1013 consecutive patients underwent sentinel lymphadenectomy for breast carcinoma. Six hundred sixty-seven patients (65.8%) received prophylaxis and isosulfan blue dye, 33 (3.3%) received prophylaxis but no dye, 12 (1.2%) received dye but no prophylaxis, and 301 (29.7%) received no prophylaxis or dye. Blue urticaria and facial edema were observed in 3 (0.5%) of 667 patients receiving prophylaxis and dye and in 1 (8.3%) of 12 patients receiving dye but no prophylaxis. There were no episodes of hypotension, and no patients required vasopressors, ventilatory support, or intensive care observation. Adverse reactions to agents other than blue dye were observed in 2 (0.3%) of 667 patients receiving prophylaxis and dye and in 3 (1.0%) of 301 receiving no prophylaxis and no dye (P = 0.1773). CONCLUSIONS: Preoperative prophylaxis was found to reduce the severity, but not the overall incidence, of adverse reactions to isosulfan blue dye. No life-threatening reactions were noted in patients treated with preoperative prophylaxis. Based on these results, the authors now routinely recommend administration of prophylaxis to patients receiving isosulfan blue for lymphatic mapping and sentinel lymph node biopsy.

Aged↗
PubMed2005

Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks.

PURPOSE: To determine the impact a change in schedule of paclitaxel administration from once every 3 weeks to frequent administration would have on the pathologic complete response (pCR) rate in the breast and lymph nodes for patients with invasive breast cancer treated with primary systemic chemotherapy (PST). PATIENTS AND METHODS: Patients with clinical stage I-IIIA breast cancer were randomly assigned to receive PST of paclitaxel doses administered either weekly (for a total of 12 doses of paclitaxel) or once every 3 weeks (four cycles), followed by four cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC) in standard doses every 3 weeks. Two different doses of paclitaxel were used based on lymph node status defined by ultrasound and fine needle aspiration. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after completion of all chemotherapy. RESULTS: A total of 258 patients were randomly assigned to receive doses of paclitaxel administered either weekly or once every 3 weeks, followed by FAC. Of these 258 patients, 110 patients had histologic lymph node involvement and 148 patients had clinical N0 disease. Weekly paclitaxel followed by FAC was administered to 127 patients and once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients. Clinical response to treatment was similar between groups (P = .25). Patients receiving weekly paclitaxel had a higher pCR rate (28.2%) than patients treated with once-every-3-weeks paclitaxel (15.7%; P = .02), with improved breast conservation rates (P = .05). CONCLUSION: The change in schedule of paclitaxel from once every 3 weeks to a more frequent administration significantly improved the ability to eradicate invasive cancer in the breast and lymph nodes.

Adult↗
PubMed2005

Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence.

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.

Adult↗
PubMed2005

Improving local control with breast-conserving therapy: a 27-year single-institution experience.

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.

Age Factors↗
PubMed2005

Predictors of locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy.

PURPOSE: To identify the clinical and pathologic factors predictive of locoregional recurrence (LRR) after neoadjuvant chemotherapy, mastectomy, and radiotherapy. METHODS AND MATERIALS: We retrospectively reviewed the hospital records of 542 patients treated on six consecutive institutional prospective trials using neoadjuvant chemotherapy and postmastectomy radiotherapy. The clinical stage (American Joint Committee on Cancer, 1988) was Stage II in 17%, Stage IIIA in 30%, Stage IIIB in 43%, and Stage IV (ipsilateral supraclavicular disease) in 10%. All LRRs were considered events, irrespective of the timing to distant metastases. RESULTS: The median follow-up was 70 months. The 5-year and 10-year actuarial LRR rate was 9% and 11%, respectively. The clinical factors associated with LRR included combined clinical stage, clinical T stage, ipsilateral supraclavicular nodal disease, chemotherapy response, physical examination size after chemotherapy, and no tamoxifen use (p < or = 0.04 for all factors). The pathologic predictors of LRR included the number of positive nodes, dissection of <10 nodes, multifocal/multicentric disease, lymphovascular space invasion, extracapsular extension, skin/nipple involvement, and estrogen receptor-negative disease (p <or = 0.05 for all factors). Multivariate Cox regression analysis revealed that five factors independently predicted for LRR: skin/nipple involvement, supraclavicular nodal disease, no tamoxifen use, extracapsular extension, and estrogen receptor-negative disease (hazard ratio, 2.1-2.8; p < or = 0.02 for all factors). The 10-year LRR rate was only 4% for patients with one or none of these five independent factors, 8% for those with two factors, and 28% for those with three or more factors (p < 0.0001). CONCLUSION: Although the long-term rate of LRR after neoadjuvant chemotherapy, mastectomy, and radiotherapy is low, we identified a number of factors that correlated independently with greater rates of LRR. Patients with three or more of these factors may benefit from research protocols investigating alternative treatment strategies.

Adult↗
PubMed2005

Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry.

BACKGROUND: The ideal pathologic assessment of sentinel lymph nodes (SLNs) in patients with breast carcinoma remains controversial. The authors evaluated how detailed assessment of SLNs using immunohistochemistry (IHC) and serial sectioning would affect treatment decisions and outcomes in patients with breast carcinoma who had negative SLNs on standard hematoxylin and eosin staining. METHODS: The SLNs from patients who were treated between June 1998 and June, 1999 and who had negative lymph node status determined by hematoxylin and eosin staining (n = 84 patients) were evaluated further with serial sectioning and cytokeratin IHC. Patients were offered adjuvant therapy based on primary tumor factors. RESULTS: The median patient age was 57 years, and the median tumor size was 1.2 cm. At a median follow-up of 40.2 months, 81 patients (96%) were alive with no evidence of disease, 1 patient was alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. Fifteen patients (18%) had micrometastases identified on IHC. Of the total 84 patients, information regarding adjuvant therapy was not available for 5 patients. Of the remaining 79 patients, 10 patients (13%) were not offered adjuvant chemotherapy but had positive SLN status determined by IHC. SLN status based on IHC evaluation did not correlate with age (P = 0.077), tumor size (P = 0.717), grade (P = 0.148), estrogen receptor status (P = 1.000), or lymphovascular invasion (P = 0.274). Furthermore, IHC-detected positive SLN status did not correlate with distant metastasis (P = 0.372) or overall or distant metastasis-free survival (P = 0.543 and P = 0.540, respectively). CONCLUSIONS: Although the finding of SLN micrometastases by IHC may change management in > 12% of patients, preliminary results suggested that such micrometastases do not affect outcomes significantly.

Adult↗
PubMed2005

Lower and central tumor location correlates with lymphoscintigraphy drainage to the internal mammary lymph nodes in breast carcinoma.

BACKGROUND: Radiation to the internal mammary chain (IMC) may be indicated for breast carcinoma patients with positive axillary sentinel lymph nodes (SLNs) and lymphoscintigraphic evidence of drainage to the IMC. The purpose of this study was to identify predictors of IMC drainage in patients with positive axillary SLNs. METHODS: The records of 297 breast carcinoma patients with positive axillary SLNs and preoperative lymphoscintigraphy were reviewed between 1995 and 2002. Radiolabeled colloid was injected peritumorally with lymphoscintigraphy performed 30-60 minutes later. Drainage to the regional nodes of 279 patients was seen on lymphoscintigraphy. Associations among patient and tumor-related factors and drainage to the IMC were examined. RESULTS: Drainage to the IMC on lymphoscintigraphy was seen in 63 patients (21%). IMC drainage only occurred in 4 patients, and 59 patients had both axillary and IMC drainage. The only variable that correlated with IMC drainage was tumor location (P = 0.017). Rates of drainage to the IMC were 14.1% for upper outer quadrant (n = 128), 16.7% for upper inner quadrant (n = 30), 31.6% for lower outer quadrant (n = 19), 42.9% for lower inner quadrant (n = 14), and 28.4% for central tumors (n = 88). IMC drainage rates differed significantly between upper and lower tumors (lower 36.4% vs. central 28.4% vs. upper 14.6%, P = 0.003) but not between medial and lateral tumors (medial 25.0% vs. central 28.4% vs. lateral 16.3%, P = 0.077). CONCLUSIONS: Patients with tumors in the lower or central breast and positive axillary SLNs have increased incidence of drainage to the IMC. Preoperative lymphoscintigraphy can help to define the nodal basins at risk for harboring disease.

Adult↗
PubMed2005

Paget's disease of the breast: there is a role for breast-conserving therapy.

BACKGROUND: The optimal surgical management of Paget's disease of the breast remains to be defined. Mastectomy has been the standard of care, but several institutions have recently advocated breast-conserving surgery, particularly for patients with minimal disease. In an effort to develop rational treatment guidelines, we examined our institutional experience with Paget's disease of the breast. METHODS: Patients with Paget's disease of the breast who had surgical therapy at our institution between 1949 and 1993 were reviewed. In addition to patient and tumor characteristics, charts were reviewed for treatment modalities, locoregional recurrence patterns, and survival. Subgroups were compared for differences in survival in both univariate and multivariate analyses. RESULTS: A total of 104 patients met the study criteria. The most common presenting symptoms were nipple discharge and eczematous changes of the nipple/areola complex. Ninety-seven patients (93.2%) had an underlying invasive or noninvasive cancer associated with Paget's disease. Ninety-two patients (88.5%) underwent mastectomy, and 12 (11.5%) had a breast-conserving procedure. On univariate analysis, patients with age <60 years at diagnosis, stage II disease, positive lymph nodes, invasive disease, or a palpable mass had significantly lower 10-year disease-specific and recurrence-free survival. There were four locoregional recurrences (three after mastectomy and one after breast conservation). There were no significant differences in overall, disease-specific, or recurrence-free survival according to the type of surgery. CONCLUSIONS: Paget's disease of the breast is almost always associated with an underlying breast cancer. Breast-conserving approaches result in local control and survival rates similar to those achieved with mastectomy.

Adult↗
PubMed2005

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.

Adult↗
PubMed2005

Breast conservation after neoadjuvant chemotherapy.

BACKGROUND: The appropriate selection criteria for breast-conserving therapy (BCT) after neoadjuvant chemotherapy are poorly defined. The purpose of the current report was to develop a prognostic index to help refine selection criteria and to serve as a general framework for clinical decision-making for patients treated by this multimodality approach. METHODS: From a group of 340 patients treated with BCT after neoadjuvant chemotherapy, the authors previously determined 4 statistically significant predictors of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR): clinical N2 or N3 disease, residual pathologic tumor size > than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The M. D. Anderson Prognostic Index (MDAPI) was developed by assigning scores of 0 (favorable) or 1 (unfavorable) for each of these 4 variables and using the total to give an overall MDAPI score of 0-4. RESULTS: The MDAPI stratified the 340 patients into 3 subsets with statistically different levels of risk for IBTR and LRR after neoadjuvant chemotherapy and BCT. Actuarial 5-year IBTR-free survival rates were 97%, 88%, and 82% for patients in the low (MDAPI overall score 0 or 1, n=276), intermediate (MDAPI score 2, n=43), and high (MDAPI score 3 or 4, n=12) risk groups, respectively (P<0.001). Corresponding actuarial 5-year LRR-free survival rates were 94%, 83%, and 58%, respectively (P<0.001). CONCLUSIONS: Patients with an MDAPI score of 0 or 1, which made up 81% of the study population, had very low rates of IBTR and LRR. The MDAPI enabled the identification of a small group (4%) of patients who are at high risk for IBTR and LRR and who may benefit from alternative locoregional treatment strategies.

Adult↗
PubMed2005

Significant differences in nipple aspirate fluid protein expression between healthy women and those with breast cancer demonstrated by time-of-flight mass spectrometry.

New approaches are needed for the early detection of breast cancer. Proteomic profiling technologies, such as surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS), may be able to identify tumor markers in biological fluids. The objective of this study was to determine whether there are differences in protein expression patterns in nipple aspirate fluid (NAF) from the cancerous and noncancerous breasts of patients with unilateral breast cancer and the breasts of healthy volunteers. Paired NAF samples were obtained from 23 women with stage I or II unilateral invasive breast carcinoma and five healthy female volunteers. Aliquots of the samples were applied to SELDI Protein-chip arrays (WCX2 and IMAC3-Cu++), and protein expression was analyzed using time-of-flight MS. A total of 463 distinct peaks were detected and analyzed. In breast cancer patients, no differences in protein expression were identified between the breast with the intact primary carcinoma and the contralateral noncancerous breast. Seventeen peaks were overexpressed in cancer-bearing breasts compared to breasts of healthy volunteers (p < 0.0005). When spectra from the nontumor-bearing breasts of breast cancer patients were compared with spectra from breasts of healthy volunteers, two peaks that were overexpressed in breast cancer patients and one peak that was underexpressed in breast cancer patients were detected (p < 0.0027). SELDI-MS was able to identify differences in the phenotypic proteomic profile of NAF samples obtained from patients with early-stage breast cancer and healthy women. Proteomic screening techniques such as SELDI-MS analysis of NAF may be useful for breast cancer screening and diagnosis.

Biopsy, Needle↗
PubMed2005

Sentinel lymph node dissection provides axillary control equal to complete axillary node dissection in breast cancer patients with lobular histology and a negative sentinel node.

OBJECTIVE: Invasive lobular carcinoma (ILC) presents special challenges to treating physicians because of the diffuse infiltrative growth pattern. As sentinel lymph node dissection (SLND) is rapidly replacing axillary lymph node dissection (ALND) in the management of patients with early-stage breast cancer, we sought to evaluate the safety of SLND in providing axillary control in breast cancer patients with lobular histology and a negative sentinel node. METHODS: We identified 239 patients with T1-2,N0,M0 lobular breast cancer from the prospective databases of 2 institutions; all were treated between March 1994 and December 2003. RESULTS: A total of 202 patients had SLND and 37 had SLND followed by ALND. There was no significant difference between the 2 groups with respect to tumor size, presence of lymphovascular invasion, estrogen receptor (ER)/progesterone receptor (PR) and HER-2/neu status, type of breast surgery, margin status, or nuclear grade. Use of chemotherapy, radiation, and hormonal therapy was not significantly different between groups. At a median follow-up of 48 months in the ALND group and 26 months in the SLND group (range 6 to 80 months), none of the 202 patients in the SLND group had experienced an axillary recurrence, while 2 (5.4%) of the 37 patients who underwent ALND had experienced an axillary recurrence. CONCLUSIONS: SLND provided axillary control equivalent to that of ALND for patients with lobular breast cancer. SLND alone appears to be adequate axillary management of patients with lobular breast cancer and a negative sentinel node.

Axilla↗
PubMed2005

Determinants of mastectomy in breast conservation therapy candidates.

BACKGROUND: Although underused, breast conservation therapy (BCT) is an accepted method for treatment of noninvasive and early breast cancer. The purpose of this analysis was to identify factors associated with receiving mastectomy when eligible for BCT. METHODS: From a recent experience, 397 patients at the University of Texas M. D. Anderson Cancer Center presented with clinical stage 0, I, or II breast cancer. Demographics and tumor characteristics of patients who underwent BCT versus mastectomy were compared. RESULTS: Of 293 BCT candidates, 203 patients (69%) underwent BCT and 90 patients (31%) received a mastectomy. Of those 90 patients, 66 patients (73%) had documented concerns about receiving BCT. Multivariate analyses showed that widow status was a factor associated with receiving mastectomy at presentation (P = .04). CONCLUSIONS: The majority of BCT candidates with early stage breast cancer undergo BCT. In our study, widow status was a predictive factor of mastectomy in BCT candidates.

Breast Neoplasms↗
PubMed2005

Patterns of participation and successful patient recruitment to American College of Surgeons Oncology Group Z0010, a phase II trial for patients with early-stage breast cancer.

BACKGROUND: Historically, fewer than 5% of cancer patients enroll in clinical trials and lack of physician participation is a contributing factor. In 1999, the American College of Surgeons Oncology Group (ACOSOG) conducted a multicenter breast cancer trial evaluating the prognostic value of sentinel lymph node (SLN) and bone marrow micrometastases. This report elucidates factors influencing patient accrual. METHODS: Demographics of investigators (N = 198) and their success in accruing patients (N = 5327) were reviewed. ACOSOG Breast Committee members (N = 1136) were surveyed to identify factors influencing participation. RESULTS: Surgeons from 126 institutions participated in Z0010 (academic [48%], teaching-affiliated [20%], and community [29%] practices), and 28% of surgeons accrued 75% of the subjects. Twenty-four percent of surgeons accrued 75% of minority patients. Female surgeons accrued 24% of patients and accounted for 30% of investigators. On survey, 16% of respondents reported no prior experience with clinical trials and a number of factors were identified that influenced participation. CONCLUSIONS: ACOSOG successfully accrued 5327 patients to a SLN trial with surgeon participation from all practice settings. However, significant barriers to participation remain.

Attitude of Health Personnel↗
PubMed2005

Predictors of invasive breast cancer in patients with an initial diagnosis of ductal carcinoma in situ: a guide to selective use of sentinel lymph node biopsy in management of ductal carcinoma in situ.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in patients with an initial diagnosis of ductal carcinoma in situ (DCIS) has not been well defined. The purpose of our study was to determine when the risk of finding invasive disease on final pathology in patients with an initial diagnosis of DCIS was sufficiently high to justify use of SLNB. STUDY DESIGN: The records of 398 consecutive patients from our prospective database with an initial diagnosis of DCIS, treated between July 1999 and December 2002, were analyzed. Associations between clinical and pathologic factors and patient selection for SLNB and outcomes were analyzed for significance using univariate and multivariate analyses. RESULTS: Of the 398 patients, 80 (20%) were found to have invasive disease on final pathology. Multivariate analysis revealed 4 independent predictors of invasive cancer on final pathology: 55 years of age or younger (odds ratio [OR], 2.19; p = 0.024), diagnosis by core-needle biopsy (OR, 3.76; p = 0.006), mammographic DCIS size of at least 4 cm (OR, 2.92; p = 0.001), and high-grade DCIS (OR, 3.06; p = 0.002). A total of 141 patients (35%) underwent SLNB as a component of their initial operation. Multivariate analysis revealed that the presence of comedonecrosis (OR, 2.69; p = 0.007) and larger mammographic DCIS size (OR, 1.18; p = 0.0002) were independent predictors of patients' undergoing SLNB. Of these 141 patients, 103 (73%) were diagnosed by core-needle biopsy, 42 (30%) had invasive disease on final pathology, and 14 (10%) had a positive sentinel lymph node: 12 (86%) by hematoxylin and eosin staining and 2 by immunohistochemistry. The only independent predictor of a positive SLN was the presence of a palpable tumor (OR, 4.28, p = 0.042). Of these 14 patients with a positive sentinel node, only 11 (79%) had invasive cancer on final pathology. CONCLUSIONS: SLNB should not be performed routinely for all patients with an initial diagnosis of DCIS. Risks and benefits of SLNB should be discussed with patients who are younger, are diagnosed by core-needle biopsy, or have large or high-grade DCIS.

Adult↗
PubMed2005

Cyclin E as a prognostic and predictive marker in breast cancer.

Breast cancer is the most common cancer in American women and is second only to lung cancer as the leading cause of death among women with solid tumors. Although chemotherapy and hormonal therapy are widely used in the primary treatment of breast cancer, appropriate selection of patients for such treatment remains challenging. Traditional prognostic factors --such as age, lymph node status, tumor size, tumor grade, and hormone receptor status--have been useful in assessing the risk for development of metastatic disease and these have been incorporated into a program that is available online for risk assessment (www.adjuvantonline.com). Molecular markers have not been incorporated into this schema but certainly have the potential for further refining risk assessment. Once the risk of recurrence is established for each patient, this can then be used to determine the potential effectiveness of hormonal therapy, chemotherapy, or the combination of these treatments. While the use of this web-based system has certainly empowered physicians and patients in making adjuvant therapy decisions, it is inadequate for precise stratification of patient cohorts into responders versus non-responders to systemic agents. Identification of accurate prognostic indicators and predictors of response have the potential to profoundly impact treatment selection for individual patients. Further, identification of prognostic factors with underlying biology that can serve as therapeutic targets will be important for identification and treatment of high-risk patients. Here we discuss the role of cyclin E as a prognostic marker and predictive factor in breast cancer management and the potential to use this marker as a target for therapy.

Biomarkers, Tumor↗
PubMed2005

Role for the double-stranded RNA-activated protein kinase PKR in Ad-TNF-alpha gene therapy in esophageal cancer.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is a cytokine with direct antitumor activity. Clinical trials with TNF-alpha have been limited because of the severe side effects of systemic administration. Gene therapy with an adenoviral vector allows delivery of high local doses of TNF-alpha. Activation of protein kinase R (PKR) has been implicated as a general transducer of apoptosis in response to a variety of different stimuli including TNF-alpha. We, therefore, evaluated the role of PKR in Ad-TNF-alpha-induced apoptosis in esophageal cancer cells. METHODS: A tetracycline-responsive adenoviral vector was used to transfect the TNF-alpha gene (Ad-TNF-alpha) into human esophageal cancer cell lines Bic1, Seg1 and TT, as well as in transformed PKR(+/+) and PKR(-/-) early-passage mouse embryo fibroblasts. Ad-luciferase, Ad-Bak, and mock infection with phosphate buffered saline solution were used as controls. Gene expression was determined by Western blot analysis. Apoptosis was detected by propidium iodide staining and fluorescence-activated cell sorter analysis. RESULTS: Overexpression of TNF-alpha in the lysate was evident in all cell lines treated with Ad-TNF-alpha. Treatment with Ad-TNF-alpha was associated with PKR upregulation and induction of apoptosis. Inhibition of TNF-alpha expression by tetracycline resulted in downregulation of PKR and decreased apoptosis. Transduction of PKR(+/+) and PKR(-/-) mouse embryo fibroblasts with Ad-TNF-alpha demonstrated that Ad-TNF-alpha-induced apoptosis was mediated in part through a PKR-dependent process. CONCLUSIONS: These results suggest that Ad-TNF-alpha-mediated apoptosis in esophageal cancer cell lines is dependent in part on PKR upregulation. Strategies to enhance PKR upregulation may allow increased Ad-TNF-alpha antitumoral activity in the treatment of esophageal cancer.

Adenocarcinoma↗