Biomedical subjects

D Kay Blanchard

Publications and source records attributed to D Kay Blanchard.

5 recordsLinked to original sources

PubMed2006

Cytotoxic gene therapy for human breast cancer in vitro.

BACKGROUND: Transcription factor PDX-1 is expressed by human pancreatic and breast cancers. Although cytotoxicity of PDX-1-directed RIP-TK/GCV gene therapy to pancreatic cancer cells has been demonstrated, the efficacy of this treatment in breast cancer cells is unknown. The purpose of this study was to determine the expression of PDX-1 and its effect on RIP activation in two human breast cancer cell lines, AU565 and T47D. We also investigated the efficacy of RIP-TK/GCV gene therapy and examined whether exogenous PDX-1 to would enhance its cytotoxic effect. MATERIALS AND METHODS: RT-PCR was used to determine PDX-1 expression. Gene constructs RSVLacZ and RIPLacZ were used for transient transfection and LacZ expression was determined using reporter assays. T47D cells were also transfected with adenoviral vectors. Cells were transfected with RIP-TK and the suboptimal level of GCV was determined for each cell line. Following GCV treatment, cytotoxicity was measured using MTS assays. The effect of exogenous PDX-1 on LacZ expression and RIP-TK cytotoxicity was determined. RESULTS: PDX-1 mRNA was expressed in human breast cancer cells and activated the RIP. Exogenous PDX-1 enhanced LacZ expression in AU565 cells but not in T47D cells. Adenoviral transfection was more efficient in T47D cells than non-viral transfection. RIP-TK treatment was cytotoxic to AU565 and T47D cells and this effect was enhanced by exogenous PDX-1 with both transfection methods. CONCLUSIONS: RIP-TK/GCV therapy is cytotoxic to human breast cancer cells and exogenous PDX-1 enhances cytotoxicity. In vivo studies are necessary to determine the tumor specificity and efficacy of this treatment.

Adenoviridae↗

PubMed2004

Retrospective study of women presenting with axillary metastases from occult breast carcinoma.

Although palpable axillary lymphadenopathy is most often related to benign disorders, it may be a harbinger of an underlying advanced malignancy. Fewer than 1% of patients diagnosed with breast cancer initially present with axillary metastases as their only clinical manifestation. This study represents the Mayo Clinic experience with women with occult breast cancer who presented with axillary metastases. Among a group of 44 women undergoing axillary biopsy for a palpable mass, 35 had histologic evidence of a metastatic carcinoma of primary breast cancer origin. Our retrospective analysis focused on the workup, identification, treatment, and outcome of these 35 women. All 35 women had a palpable axillary nodule, no dominant breast mass, and normal mammograms and chest radiographs. Histologic analysis of the axillary node revealed a probable breast cancer in all patients. Long-term follow-up was available for 33 patients (mean 71.5 months, range 4-252 months). Mastectomy was performed as part of the primary treatment in 18 patients (51%), and among them a primary breast tumor was found in 6 (33%). Of the women who underwent mastectomy (n = 18) and for whom follow-up data were available (n = 17), six developed tumor recurrence (35%), and four died of their disease (24%). Among the patients who did not undergo mastectomy (n = 17) as their primary treatment, follow-up revealed that 12 (of 16) patients developed recurrent disease (75%), and 11 patients died of breast carcinoma (69%). Despite extensive clinical and radiologic evaluation, a primary tumor was not initially located in any of the 35 women with axillary metastases from a presumed occult breast carcinoma. As a consequence of aggressive surgical intervention, six primary breast cancers were located in mastectomy specimens, and those 17 patients followed after mastectomy fared significantly better than the 16 patients without mastectomy (p = 0.047).

Adult↗

PubMed2003

Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer.

HYPOTHESIS: Axillary relapse in node-negative patients staged with sentinel lymph node (SLN) biopsy alone is no more frequent than in patients treated with standard axillary dissection. Morbidity is less for patients who had SLN biopsy. DESIGN, SETTING, AND PATIENTS: Between October 14, 1997, and August 31, 2001, 1253 consecutive women with primary invasive breast cancer were prospectively entered into an SLN biopsy database. Completion axillary dissection was performed in 164 patients after SLN biopsy as part of a training protocol. INTERVENTIONS: Patients were contacted by questionnaire or telephone to determine breast cancer relapse; presence of arm lymphedema, arm pain, axillary infection, or seroma formation; and tumor recurrence or death. MAIN OUTCOME MEASURES: chi2 or Fisher exact tests and Wilcoxon rank sum tests were used to analyze categorical and continuous variables. Logistic regression was used to analyze morbidity. RESULTS: Of 1253 women, 894 (71%) were node negative by SLN biopsy alone (n = 730 [82%]) or SLN biopsy and completion axillary dissection (n = 164 [18%]). Questionnaires were completed by 776 patients (87%). Mean +/- SD follow-up was 2.4 +/- 0.9 years. Patients with axillary dissections reported a significantly higher occurrence of arm lymphedema (34%), arm pain (38%), seroma formation (24%), and infection (9%) vs SLN biopsy-only patients (6%, 14%, 7%, and 3%, respectively). One axillary relapse (0.1%) occurred during follow-up of 685 women who underwent SLN biopsy only. CONCLUSIONS: With intermediate-term follow-up, there was 1 axillary recurrence in 685 SLN node-negative women, supporting use of SLN biopsy as an accurate method for staging breast cancer. Biopsy of the SLN was associated with significantly less morbidity than completion axillary dissection.

Aged↗

PubMed2003

Primary nonphylloides breast sarcomas.

BACKGROUND: The prevalence of primary breast sarcoma is low, occurring in fewer than 1% of women with breast malignancies. The purpose of this study was to examine the presentation, treatment, and prognosis of patients presenting with these neoplasms. METHODS: This was a retrospective review of patients with a primary breast sarcoma treated at Mayo Clinic, Rochester, Minnesota, between 1975 and 2001. Follow-up information was obtained. RESULTS: Of the 55 patients, 17 had breast-conserving therapy and 38 women had mastectomy. The mean patient age at presentation was 52 years (range 22 to 82). The types of sarcoma included angiosarcoma (18), malignant fibrous histiocytoma (11), stromal sarcoma (8), liposarcoma (4), leiomyosarcoma (4), dermatofibrosarcoma protuberans (4), osteosarcoma (3), fibrosarcoma (2), and rhabdomyosarcoma (1). Follow-up information was available for 53 patients, with a mean follow-up of 81 months. Twenty-nine of 53 patients (55%) developed recurrent sarcoma, and 23 patients (43%) died of their disease. Twenty-seven patients had no evidence of recurrence, and 3 patients were alive with disease at last follow-up. Overall median survival of patients with breast sarcoma was 58 months. Patients with angiosarcoma had a poorer outcome than other sarcoma patients. Twelve of 18 patients (67%) died of angiosarcoma, compared with 11 of 32 patients (34%) of all other sarcoma patients combined. Of 34 patients who did not receive adjuvant chemotherapy or radiation, 13 died of their disease (38%), as compared with 10 of 16 patients (63%) who did receive adjuvant therapy. CONCLUSIONS: While primary nonphylloides breast sarcomas are rare tumors, their treatment and prognosis are poor. Adjuvant chemotherapy and radiation did not improve survival in this report. Surgical extirpation remains the only effective treatment.

Adult↗

PubMed2002

Radiation-induced breast sarcoma.

BACKGROUND: The purpose of this study was to examine the presentation, treatment, and prognosis of patients with radiation-induced sarcomas after adjuvant radiotherapy for breast cancer. METHODS: This was a retrospective review from 1975 to 2001 of patients who presented with a sarcoma in an irradiated field after surgical treatment for breast cancer. RESULTS: Thirty-four women were included. Six had undergone breast-conserving therapy and 28 had mastectomy for primary breast carcinoma. All patients received postoperative radiation. The mean time to diagnosis of sarcoma was 152 months (range 40 to 372). Twenty-three of 34 patients (68%) had recurrence of the sarcoma after resection, and 22 patients (65%) died of their disease. Patients with no evidence of disease at follow-up had a mean tumor size of 4.2 cm +/- 0.7 (n = 6), compared with 8.1 cm +/- 1.2 (n = 10) for patients who died of their disease (P = 0.030). CONCLUSIONS: Radiation-induced sarcoma is a late complication of definitive treatment for breast carcinoma. The prognosis of such patients is poor, with two thirds dying of their disease. In the present series, improved survival was associated with smaller tumor size at presentation.

Adult↗