Biomedical subjects

Kelly K Hunt

Publications and source records attributed to Kelly K Hunt.

At least 19 recordsLinked to original sources

PubMed2007

Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen.

PURPOSE: Findings from our previously published phase III randomized trial showed a high pathologic complete remission (CR) rate in patients with human epidermal growth factor receptor 2-positive breast cancer after the concurrent administration of trastuzumab and paclitaxel, followed by concurrent trastuzumab and 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) preoperative chemotherapy. The safety and efficacy data of initial population were updated, with inclusion of additional experience with the same therapy. STUDY DESIGN: The initial randomized study population of 42 patients were randomly assigned to either four cycles of paclitaxel followed by four cycles of FEC or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. All data were updated through November 2005. RESULTS: Pretreatment characteristics of the initial patients and of the second cohort were similar. In the second cohort, pathologic CR rate was 54.5% (95% confidence interval, 32.2-75.6%) and the pathologic CR rate among all patients treated with chemotherapy plus trastuzumab was 60% (95% confidence interval, 44.3-74.3%). Three patients in the chemotherapy only group have recurred, and one has died. There has been no recurrences in the patients randomized to chemotherapy plus trastuzumab, and the estimated disease-free survival at 1 and 3 years was 100% (P = 0.041). In additional cohort treated with chemotherapy and trastuzumab at the median follow-up of 16.3 months, no patients had recurred. No new safety concerns were observed in this study. CONCLUSION: Our expanded cardiac safety data and the updated efficacy data showed that the natural history of this subset of breast cancer patients can be substantially modified by this treatment approach.

Adult↗

PubMed2007

Surgical resection of gastrointestinal stromal tumors after treatment with imatinib.

BACKGROUND: Surgical resection of gastrointestinal stromal tumors (GISTs) has been the most effective therapy for these rare tumors. Imatinib has been introduced as systemic therapy for locally advanced and metastatic GIST. In this study, the surgical resection rates and long-term outcomes of patients treated with preoperative imatinib for locally advanced primary, recurrent, or metastatic GISTs were evaluated. METHODS: Patients were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection. RESULTS: Forty-six patients underwent surgery after treatment with imatinib. Eleven were treated for locally advanced primary GISTs for a median of 11.9 months, followed by complete surgical resection. All eleven were alive at a median of 19.5 months, and ten were free of disease. Thirty-five patients were treated for recurrent or metastatic GIST. Of these, eleven underwent complete resection. Six of the eleven patients had recurrent disease at a median of 15.1 months. All eleven patients were alive at a median of 30.7 months. Patients with a partial radiographic tumor response to imatinib had significantly higher complete resection rates than patients with progressive disease (91% vs. 4%; P < .001). Of the 24 patients with incomplete resection, 18 initially responded to imatinib but were unable to undergo complete resection after they progressed before surgery. CONCLUSIONS: Preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs. Early surgical intervention should be considered for imatinib-responsive recurrent or metastatic GIST, since complete resection is rarely achieved once tumor progression occurs.

Adult↗

PubMed2006

Is intraoperative touch imprint cytology of sentinel lymph nodes in patients with breast cancer cost effective?

BACKGROUND: Sentinel lymph nodes (SLNs) are generally evaluated postoperatively, requiring 5-7 days for assessment. SLNs can also be evaluated intraoperatively by using touch imprint cytology (TIC), thus providing the surgeon immediate feedback and allowing for concurrent completion node dissection (CND) for positive SLNs. The authors hypothesized that TIC, when compared with standard postoperative SLN assessment alone, would permit a cost-effective evaluation of SLNs in patients with clinically node-negative breast cancer. METHODS: A decision-analysis model was created to compare TIC with standard postoperative SLN assessment alone. Sensitivity and specificity of TIC were determined prospectively from 342 patients who underwent SLN biopsy assessed by both techniques. Short-term health states associated with surgical staging were defined, and utilities were estimated using EuroQol-5D. Base-case analysis was performed to estimate quality-adjusted life years and the incremental cost-effectiveness ratio. Sensitivity analyses were performed to examine stability of model parameters. RESULTS: For each tumor stage, TIC was cost effective, and for patients with larger tumors (T3 and T4), TIC was the dominant strategy. The analysis was robust to changes in sensitivity and specificity of TIC, prevalence of metastasis, probability of complications, and cost. However, when utility associated with standard SLN assessment was 0.9 or greater, this became the preferred strategy. CONCLUSIONS: TIC is cost effective for assessing SLN metastasis intraoperatively. For patients with larger tumors, it is not only more effective, but also less costly than standard SLN assessment alone. TIC may be particularly useful for patients who experience significant anxiety while awaiting results of standard SLN assessment.

Algorithms↗

PubMed2006

Retroperitoneal soft tissue sarcoma: an analysis of radiation and surgical treatment.

PURPOSE: To evaluate the clinical outcomes of patients with localized retroperitoneal soft tissue sarcoma (STS) treated with complete surgical resection and radiation. METHODS AND MATERIALS: The medical records of 83 patients were reviewed retrospectively. Sixty patients presented with primary disease and the remaining 23 had recurrence after previous surgical resection. RESULTS: With a median follow-up of 47 months, the actuarial overall disease-specific survival (DSS), distant metastasis-free survival, and local control (LC) rates were 44%, 67%, and 40%, respectively. Of the 38 patients dying of disease, local disease progression was the sole site of recurrence for 16 patients and was a component of progression for another 11 patients. Multivariate analysis indicated that histologic grade was associated with the 5-year rates of DSS (low-grade, 92%; intermediate-grade, 51%; and high-grade, 41%, p = 0.006). Multivariate analysis also indicated an inferior 5-year LC rate for patients presenting with recurrent disease, positive or uncertain resection margins, and age greater than 65 years. The data did not suggest an improved local control with higher doses of external-beam radiation (EBRT) or with the specific use of intraoperative radiotherapy (IORT). Radiation-related complications (10% at 5 years) developed in 5 patients; all had received their EBRT postoperatively. CONCLUSIONS: Although preoperative radiation therapy and aggressive surgical resection is well tolerated in patients, local disease progression continues to be a significant component of disease death. In this small cohort of patients, the use of higher doses of EBRT or IORT did not result in clinically apparent improvements in outcomes.

Adult↗

PubMed2006

Locoregional control of clinically diagnosed multifocal or multicentric breast cancer after neoadjuvant chemotherapy and locoregional therapy.

PURPOSE: The purpose was to assess whether patients with clinical multifocal or multicentric (MFMC) breast cancer determined by mammogram, ultrasound, or physical examination have inferior outcome compared with patients with clinical unicentric lesions. PATIENTS AND METHODS: We retrospectively analyzed 706 consecutive patients with stages I-III breast cancer treated at the M.D. Anderson Cancer Center (Houston, TX) from 1976 to 2003 who received neoadjuvant anthracycline-based chemotherapy followed by breast conservation therapy (BCT), mastectomy alone, or mastectomy plus postmastectomy radiation therapy. RESULTS: The mean follow-up was 66 months. At presentation, 97 of 706 patients had clinically MFMC disease (13.7%). The 5-year rate of locoregional failure was 10% for unicentric disease compared with 7% for MFMC disease (P = .78). Subset analyses of patients by treatment groups confirmed no statistical difference in locoregional control regardless of the type of locoregional treatment. Among patients with multifocal disease treated with BCT, there were no in-breast recurrences and one supraclavicular recurrence. Five-year disease-free survival and overall survival was equivalent between patients with MFMC and unicentric breast cancers. CONCLUSION: Patients with clinical MFMC breast cancer at the time of diagnosis treated with neoadjuvant chemotherapy followed by locoregional therapy have similar 5-year rates of locoregional control, disease-free survival, and overall survival as those with unicentric disease. Clinically detected MFMC disease did not predict for inferior outcome.

Adult↗

PubMed2006

Predictors of invasion in patients with core-needle biopsy-diagnosed ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy in ductal carcinoma in situ.

BACKGROUND: Among patients with core-needle biopsy (CNB)-diagnosed ductal carcinoma in situ (DCIS), the guidelines for the selection of patients to undergo sentinel lymph node (SLN) biopsy are not well defined, and many patients with no invasion undergo an unnecessary SLN biopsy. The objective of this study was to identify the predictors of invasion in patients with CNB-diagnosed DCIS and, thus, to help determine the most appropriate candidates for SLN biopsy. METHODS: The authors retrospectively evaluated 200 consecutive patients with CNB-diagnosed DCIS who underwent final excision at their institution between May 1, 2002 and June 30, 2005. Demographic data, the size and type of lesion on imaging studies, histologic features of DCIS on CNB, the number of cores taken, and the number of cores involved by DCIS were correlated with invasion on excision and SLN biopsy outcome. RESULTS: Forty-one of 200 patients (21%) had invasive carcinoma diagnosed on final excision. Parameters that correlated with invasion were a mass lesion, lesion size >1.5 cm, high nuclear grade, and the presence of lobular cancerization on CNB. A multivariate logistic regression model was developed to predict invasion. At the time of breast surgery, 103 of 200 patients (52%) underwent SLN biopsy, and 34 had invasion diagnosed on final excision. Three patients had 1 positive SLN each. CONCLUSIONS: A mass lesion, lesion size >1.5 cm, and the presence of lobular cancerization on CNB were significant, independent predictors of invasion in patients with DCIS. The authors recommended the inclusion of these predictors in the guidelines for selecting patients for SLN biopsy to reduce the number of unnecessary procedures.

Biopsy, Needle↗

PubMed2006

Selective use of sentinel lymph node surgery during prophylactic mastectomy.

BACKGROUND: Patients with invasive cancer identified at the time of prophylactic mastectomy (PM) will require axillary lymph node dissection for staging; therefore, many surgeons advocate sentinel lymph node (SLN) surgery at the time of PM. The current study investigates the invasive cancer rate in PM and evaluates factors associated with invasive cancer to guide SLN surgery use. METHODS: Patients undergoing PM at the M. D. Anderson Cancer Center between January 2000 and July 2005 were identified from a prospective database. Clinical, radiographic, and pathologic data were collected. RESULTS: A total of 409 patients (436 PM cases) were identified; 382 underwent contralateral PM (CPM) and 27 underwent bilateral PM (BPM). Cancer was identified in 22 of 436 PM cases (5%). Of these, 14 patients (64%) had ductal carcinoma in situ (DCIS). Only 8 patients (1.8%) had invasive cancer, with a mean tumor size of 5 mm (range, 2-9 mm). There was no difference in the occult cancer rate between CPM and BPM. No cases of invasive cancer were identified in the 23 patients with BRCA mutations. Significantly increased risk of invasive cancer in the PM breast was seen in postmenopausal patients (3.7%; P = .007), patients age >60 years (7.5%; P = .008), and patients with history of invasive lobular carcinoma (9.7%; P = .0002) or lobular carcinoma in situ (LCIS) (7.7%; P = .008). CONCLUSIONS: The frequency of cancer in PM is very low and the majority represents DCIS. Therefore, routine use of SLN surgery in all patients undergoing PM is not warranted. However, patients at higher risk for whom SLN surgery should be considered include older women and patients with a history of lobular cancer or LCIS.

Adult↗

PubMed2006

Development and validation of nomograms for predicting residual tumor size and the probability of successful conservative surgery with neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) increases the likelihood that breast conservation therapy for breast cancer patients will be successful. There is no available nomogram to predict breast conservation after NACT. The aim of the current study was to develop and validate nomograms for predicting residual tumor size and probability of a patient becoming eligible for breast conservation surgery after NACT. METHODS: A total of 1147 patients treated at M. D. Anderson Cancer Center (Houston, TX) and the Institut Gustave Roussy (Villejuif, France) who received anthracycline with or without paclitaxel NACT were included in the analysis. Clinicopathologic data from 1 series were used to construct logistic regression models for breast conservation and residual tumor size < 3 cm after NACT and were validated on an independent series. RESULTS: The discrimination and the calibration of the nomogram for predicting the probability of residual tumor size < 3 cm after anthracycline-based NACT were good when applied to the validation set (concordance index = 0.79; U-index = 10(-3)). The discrimination of the nomogram for predicting eligibility for breast conservation therapy was also good (concordance index = 0.67). However, the calibration had to be adjusted to take into account global rates of breast conservation surgery. A second nomogram adapted to preoperative chemotherapy regimens containing paclitaxel was established. The concordance index of the nomogram for predicting breast conservation was 0.71 (P < 10(-6)) for the independent dataset and the calibration was also good. The confrontation of both nomograms showed that predictions were highly correlated (r = 0.97), suggesting that eligibility for breast conservation therapy was independent of the preoperative chemotherapy regimen used. CONCLUSIONS: Nomograms were developed for breast cancer patients who received NACT to predict residual tumor size and whether the patient would thus become eligible for breast conservation therapy. These tools may be useful when counseling patients about treatment options, and a web-based interface is now available to help guide patients and physicians in these decisions.

Anthracyclines↗

PubMed2006

Accuracy of the combination of mammography and sonography in predicting tumor response in breast cancer patients after neoadjuvant chemotherapy.

BACKGROUND: Residual tumor size after neoadjuvant chemotherapy is an important consideration in surgical planning. We examined the accuracy of the combination of mammography and sonography in predicting pathologic residual tumor size. METHODS: Tumor size was evaluated by physical examination, mammography, and sonography at diagnosis and before surgery in 162 breast cancer patients who received neoadjuvant chemotherapy. Agreement between the predicted and the pathologic responses and the predicted and the pathologic tumor sizes was calculated. The effect of invasive lobular carcinoma, high nuclear grade, hormone receptor positivity, and the presence of an extensive intraductal component on the accuracy of mammography and sonography in predicting pathologic residual tumor size was analyzed. RESULTS: Forty-two patients (25.9%) had a pathologic complete response (pCR). Overall agreement between predicted and pathologic responses was 53% for physical examination, 67% for mammography plus sonography, and 63% for physical examination plus mammography and sonography. The sensitivity of mammography and sonography in predicting pCR was 78.6%, and the specificity was 92.5%; the accuracy was 88.9%. Residual tumor size determined by mammography and sonography correlated with pathologic residual tumor size (r = .662); pathologic tumor size was within .5 cm of predicted in 69.1% of patients. Multivariate analysis showed that pathologic residual tumor size was underestimated for lobular carcinoma and overestimated for poorly differentiated tumors. CONCLUSIONS: The combination of mammography and sonography has a high accuracy in predicting pCR after neoadjuvant chemotherapy. Agreement of residual tumor size in mammography and sonography with pathologic residual tumor size was moderate.

Adult↗

PubMed2006

The safety of breast-conserving surgery in patients who achieve a complete pathologic response after neoadjuvant chemotherapy.

BACKGROUND: The objectives of this study were to determine the locoregional recurrence (LRR) rate and to evaluate the correlation between surgical resection volume (RV) and LRR in patients with breast cancer who underwent segmental mastectomy after achieving a pathologic complete response (pCR) on neoadjuvant chemotherapy. METHODS: The authors reviewed the outcomes of all 109 patients who underwent segmental mastectomy after the complete eradication of invasive disease by neoadjuvant chemotherapy at their institution between 1987 and 2002. LRRs were recorded, and RVs after segmental mastectomy were calculated and categorized as small, medium, or large. RESULTS: At a median follow-up of 6.6 years, 3 patients (2.7%) developed LRR. In 2 of those patients, the recurrence was located in the ipsilateral breast; in the other patient, the recurrence was located in the supraclavicular lymph nodes with synchronous distant metastases. The median RV was 73.12 cm3 (range, 2.82-451.51 cm3). Large RVs (>125 cm3) were less common than small RVs (up to 70 cm3) or medium RVs (between 70 cm3 and 125 cm3; P = .009 and P<.0001, respectively). One patient with a small RV had an LRR at 4 years, and 2 patients with medium RVs had LLRs at 2.3 years and 6 years, respectively. The 5-year and 10-year LRR-free survival rates were 98.1% and 96.5%, respectively, and the corresponding overall survival rates were 96% and 92%, respectively. CONCLUSIONS: Segmental mastectomy was associated with excellent locoregional control in patients who achieved a pCR after neoadjuvant chemotherapy. Prospective studies are needed to examine whether decreasing the RVs in this patient population leads to an increased LRR rate.

Adult↗

PubMed2006

The effect of preoperative radiotherapy and reconstructive surgery on wound complications after resection of extremity soft-tissue sarcomas.

BACKGROUND: Major wound complications (MWCs) are frequent after preoperative radiotherapy (RT) for extremity soft-tissue sarcoma (STS). We examined the rate of MWCs at a single institution with readily available reconstructive surgery. METHODS: The medical records of consecutively treated extremity STS patients treated with preoperative external-beam RT and surgical resection from June 1996 through February 2003 were reviewed. Patients underwent RT (median 50 Gy), followed by resection 4-8 weeks later. Patients believed to be at higher risk for MWC underwent wound closure by the reconstructive surgery service (RSS). MWCs included secondary operation, invasive procedure, hospital readmission, or persistent deep packing or dressing changes. RESULTS: A total of 173 patients underwent preoperative RT. Median age was 54 years; 51% were female; 80% had lower extremity STS. Wound closure was performed by the primary surgeon in 91 cases (53%). The RSS performed wound closure in the remaining 82 patients (47%). One or more MWCs occurred in 55 patients (32%). Wound complications were more likely in patients with lower extremity (49/138, 36%) than upper extremity (6/35, 17%) STS (P = 0.03). Among patients with lower-risk wounds closed by the primary surgical team, 29 (32%) experienced MWC, whereas in the higher-risk patients closed by the RSS, MWC occurred in 26 (32%). CONCLUSIONS: MWCs are frequent after preoperative RT and occur more commonly in patients with lower extremity tumors. The MWC rate observed in a single-institution setting was comparable to that observed in the preoperative therapy arm of a multicenter Canadian trial. Patients believed to be at higher risk for MWCs undergoing RSS closure have MWC rates comparable to those with lower-risk wounds closed by the primary team.

Adolescent↗

PubMed2006

Comparative analysis of sentinel lymph node operation in male and female breast cancer patients.

BACKGROUND: Male breast cancer accounts for < 1% of breast cancers. Sentinel lymph node (SLN) operation is commonly used in the evaluation of female breast cancer patients. The purpose of this study was to determine whether SLN operation is as feasible and accurate in male patients compared with female patients. STUDY DESIGN: Between 1999 and 2005, 30 men and 2,784 women underwent SLN operation. Clinical and pathologic data were reviewed and statistical analysis performed. RESULTS: Men presented at an older age (p = 0.005) and with larger tumors than women (p = 0.04). The SLN was identified in 100% of men and in 98.3% of women (p = NS). The mean number of SLNs harvested was 3.5 in men and 3.0 in women (p = NS). The incidence of positive SLNs was higher in men (37.0% versus 22.3%), although this did not reach statistical significance (p = 0.1). In patients with a positive SLN there were additional non-SLNs positive in 62.5% of men, compared with 20.7% in women (p = 0.01). The median size of the largest lymph node metastasis was 10 mm in men and 3 mm in women (p = 0.03). CONCLUSIONS: SLN operation in clinically node-negative men is feasible and accurate. Male breast cancer patients present at an older age and with larger tumors than female breast cancer patients. Male patients have higher nodal tumor burden reflected in a larger size of nodal metastasis and increased risk of harboring additional disease in axillary lymph nodes when the SLN is positive. Intraoperative SLN evaluation should be considered in the surgical management of male breast cancer.

Adenocarcinoma↗

PubMed2006

Comparison of risk of local-regional recurrence after mastectomy or breast conservation therapy for patients treated with neoadjuvant chemotherapy and radiation stratified according to a prognostic index score.

PURPOSE: We previously developed a prognostic index that stratified patients treated with breast conservation therapy (BCT) after neoadjuvant chemotherapy into groups with different risks for local-regional recurrence (LRR). The purpose of this study was to compare the rates of LRR as a function of prognostic index score for patients treated with BCT or mastectomy plus radiation after neoadjuvant chemotherapy. METHODS: We retrospectively analyzed 815 patients treated with neoadjuvant chemotherapy, surgery, and radiation. Patients were assigned an index score from 0 to 4 and given 1 point for the presence of each factor: clinical N2 to N3 disease, lymphovascular invasion, pathologic size>2 cm, and multifocal residual disease. RESULTS: The 10-year LRR rates were very low and similar between the mastectomy and BCT groups for patients with an index score of 0 or 1. For patients with a score of 2, LRR trended lower for those treated with mastectomy vs. BCT (12% vs. 28%, p=0.28). For patients with a score of 3 to 4, LRR was significantly lower for those treated with mastectomy vs. BCT (19% vs. 61%, p=0.009). CONCLUSIONS: This analysis suggests that BCT can provide excellent local-regional treatment for the vast majority of patients after neoadjuvant chemotherapy. For the few patients with a score of 3 to 4, LRR was >60% after BCT and was <20% with mastectomy. If these findings are confirmed in larger randomized studies, the prognostic index may be useful in helping to select the type of surgical treatment for patients treated with neoadjuvant chemotherapy, surgery, and radiation.

Adult↗

PubMed2006

Use of lymphoscintigraphy defines lymphatic drainage patterns before sentinel lymph node biopsy for breast cancer.

BACKGROUND: Lymphoscintigraphy (LSG) can identify lymphatic drainage patterns before sentinel lymph node (SLN) biopsy is performed in patients with early-stage breast cancer, but the importance of extraaxillary SLNs seen on LSG is unknown. We assessed whether drainage patterns seen on LSG were associated with histologic findings in axillary SLNs recovered at SLN biopsy. STUDY DESIGN: From a prospectively maintained database, we identified 1,201 clinically node-negative patients with invasive breast cancer who underwent preoperative LSG and axillary SLN biopsy. Patient and tumor characteristics, LSG results, and final SLN pathology results were examined. RESULTS: LSG showed drainage to internal mammary (IM) nodes in 1.6% of patients, axillary nodes in 68.1%, both IM and axillary nodes in 19.8%, and no drainage in 10.3%. Drainage to IM nodes was observed for tumors in all quadrants of the breast. Patients with IM drainage had a younger median age than patients without IM drainage (51.8 versus 58.3 years, respectively; p < 0.001). The intraoperative axillary SLN identification rate was higher when axillary drainage was observed on LSG than when it was not observed (98.7% versus 93.0%, respectively; p < 0.001), but the LSG drainage pattern was not associated with pathologic status of the SLN or number of metastatic SLNs. At a median followup of 32 months, 4 patients had regional nodal recurrence. CONCLUSIONS: Almost one-fourth of patients had lymphatic drainage to the extraaxillary lymph nodes, particularly the IM nodes, seen on LSG. Extraaxillary drainage seen on LSG did not preclude identification of axillary SLNs at operation. Longterm followup of patients with lymphoscintigraphic evidence of extraaxillary drainage is needed to determine whether regional and systemic recurrence patterns differ in these patients.

Adult↗

PubMed2006

Human interleukin 24 (MDA-7/IL-24) protein kills breast cancer cells via the IL-20 receptor and is antagonized by IL-10.

The melanoma differentiation-associated gene-7 (mda-7/IL-24) is a unique member of the interleukin 10 (IL-10) family of cytokines, with ubiquitous tumor cell pro-apoptotic activity. Recent data have shown that IL-24 is secreted as a glycosylated protein and functions as a pro-Th1 cytokine and as a potent anti-angiogenic molecule. In this study, we analyzed the activity of Ad-mda7 and its protein product, secreted IL-24, against human breast cancer cells. We show that Ad-mda7 transduction of human breast cancer cells results in G(2)/M phase cell cycle arrest and apoptotic cell death, which correlates with secretion of IL-24 protein. Neutralizing antibody against IL-24 significantly inhibited Ad-mda7 cytotoxicity. IL-24 and IL-10 both engage their cognate receptors on breast cancer cells resulting in phosphorylation and activation of STAT3, however, IL-10 receptor binding failed to induce cell killing, indicating that tumor cell killing by IL-24 is independent of STAT3 phosphorylation. Treatment with exogenous IL-24 induced apoptosis in breast cancer cells and this effect was abolished by addition of anti-IL-24 antibody or anti-IL-20R1, indicating that bystander cell killing is mediated via IL-24 binding to the IL-20R1/IL-20R2 heterodimeric receptor complex. Co-administration of the related cytokine IL-10 inhibited killing mediated by IL-24 and concomitantly inhibited IL-24 mediated up-regulation of the tumor suppressor proteins, p53 and p27(Kip1). In summary, we have defined a tumor-selective cytotoxic bystander role for secreted IL-24 protein and identified a novel receptor-mediated death pathway in breast cancer cells, wherein the related cytokines IL-24 and IL-10 exhibit antagonistic activity.

Apoptosis↗

PubMed2006

Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <or=55 years.

DNA double-strand breaks (DSBs) may lead to genomic instability and cancer if unrepaired. Nijmegen breakage syndrome 1 (NBS1) protein is one of the key proteins that participates in recognition and repair of DSBs in humans. We hypothesized that polymorphisms of NBS1 are associated with breast cancer risk. We selected three NBS1 haplotype-tagging polymorphisms (i.e. 924T>C, 8360G>C and 30537G>C) to represent all common (>or=5%) haplotypes reported in the National Institute of Environmental Health Sciences database and to reconstruct haplotypes. In a hospital-based case-control study of 421 non-Hispanic white patients with sporadic breast cancer ( C polymorphism. Furthermore, the derived haplotypes were associated with risk in a dose-response manner as the number of variant (risk) alleles (i.e. 8360C, 924C or 30537C) increased (adjusted OR = 1.07, 95% CI = 0.78-1.46 for 1-2 variant alleles; adjusted OR = 2.47, 95% CI = 1.48-4.14 for 3-6 variant alleles; P(trend) = 0.006). These findings suggest that NBS1 polymorphisms and haplotypes may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Large studies are warranted to confirm these findings.

Aged↗

PubMed2006

Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and an intact primary tumor.

BACKGROUND: Currently, therapy for breast cancer patients with stage IV disease and an intact primary tumor is metastasis directed; the primary tumor is treated only when it causes symptoms. A recent review suggested that surgery may improve long-term survival in such patients. We evaluated the effect of surgery in such patients on long-term survival and disease progression. METHODS: We reviewed the records of all breast cancer patients treated at our institution between 1997 and 2002 who presented with stage IV disease and an intact primary tumor. Information collected included demographics, tumor characteristics, site(s) of metastases, type/date of operation, use of radiotherapy, chemotherapy and hormonal therapy, disease progression (time to progression and location of progression) in the first year after diagnosis, and last follow-up. Overall and metastatic progression-free survival were compared between surgery and nonsurgery patients. RESULTS: Of 224 patients identified, 82 (37%) underwent surgical extirpation of the primary tumor (segmental mastectomy in 39 [48%] and mastectomy in 43 [52%]), and 142 (63%) were treated without surgery. The median follow-up time was 32.1 months. After adjustment for other covariates, surgery was associated with a trend toward improvement in overall survival (P=.12; relative risk, .50; 95% confidence interval, .21-1.19) and a significant improvement in metastatic progression-free survival (P=.0007; relative risk, .54; 95% confidence interval, .38-.77). CONCLUSIONS: Removal of the intact primary tumor for breast cancer patients with synchronous stage IV disease is associated with improvement in metastatic progression-free survival. Prospective studies are needed to validate these findings.

Adult↗

PubMed2006

Proteomic analysis of nipple aspirate fluid from women with early-stage breast cancer using isotope-coded affinity tags and tandem mass spectrometry reveals differential expression of vitamin D binding protein.

BACKGROUND: Isotope-coded affinity tag (ICAT) tandem mass spectrometry (MS) allows for qualitative and quantitative analysis of paired protein samples. We sought to determine whether ICAT technology could quantify and identify differential expression of tumor-specific proteins in nipple aspirate fluid (NAF) from the tumor-bearing and contralateral disease-free breasts of patients with unilateral early-stage breast cancer. METHODS: Paired NAF samples from 18 women with stage I or II unilateral invasive breast carcinoma and 4 healthy volunteers were analyzed using ICAT labeling, sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE), liquid chromatography, and MS. Proteins were identified by sequence database analysis. Western blot analysis of NAF from an independent sample set from 12 women (8 with early-stage breast cancer and 4 healthy volunteers) was also performed. RESULTS: 353 peptides were identified from tandem mass spectra and matched to peptide sequences in the National Center for Biotechnology Information database. Equal numbers of peptides were up- versus down-regulated. Alpha2HS-glycoprotein [Heavy:Light (H:L) ratio 0.63] was underexpressed in NAF from tumor-bearing breasts, while lipophilin B (H:L ratio 1.42), beta-globin (H:L ratio 1.98), hemopexin (H:L ratio 1.73), and vitamin D-binding protein precursor (H:L ratio 1.82) were overexpressed. Western blot analysis of pooled samples of NAF from healthy volunteers versus NAF from women with breast cancer confirmed the overexpression of vitamin D-binding protein in tumor-bearing breasts. CONCLUSION: ICAT tandem MS was able to identify and quantify differences in specific protein expression between NAF samples from tumor-bearing and disease-free breasts. Proteomic screening techniques using ICAT and NAF may be used to find markers for diagnosis of breast cancer.

Biomarkers, Tumor↗