Biomedical subjects

Barbara L Smith

Publications and source records attributed to Barbara L Smith.

24 records · Page 2Linked to original sources

PubMed2003

Dose-volume analysis of radiotherapy for T1N0 invasive breast cancer treated by local excision and partial breast irradiation by low-dose-rate interstitial implant.

PURPOSE: To evaluate the toxicity of partial breast irradiation (RT) using escalating doses of low-dose-rate interstitial implant as the sole adjuvant local therapy for selected T1N0 breast cancer patients treated by wide local excision. The results of a European Organization for Research and Treatment of Cancer study have demonstrated a significant local control benefit using external beam RT to 65 Gy compared with 50 Gy. Thus, the tolerance of escalating doses of partial breast RT should be determined, because this approach may become a standard treatment for patients with early-stage breast cancer. METHODS AND MATERIALS: Between 1997 and 2001, 48 patients with T1N0M0 breast cancer were enrolled into an institutional review board-approved Phase I/II protocol using low-dose-rate brachytherapy implants after wide local excision and lymph node staging surgery. Brachytherapy was started 3-4 days after surgery at a dose rate of 50 cGy/h, using (192)Ir sources evenly spaced to cover 3 cm around the resection margins. Typically, 2-3 planes were used, with a median of 14 catheters (range 10-16). The total dose was escalated in three groups: 50 Gy (n = 19), 55 Gy (n = 16), and 60 Gy (n = 13). The implant volume was calculated and used to classify patients into quartiles: 76-127 cm(3) (n = 12), 128-164 cm(3) (n = 12), 165-204 cm(3) (n = 12), and >204 cm(3) (n = 12). Cosmesis, patient satisfaction, treatment-related complications, mammographic abnormalities, rebiopsies, and disease status were recorded at each scheduled patient visit. RESULTS: The median follow-up for all patients was 23.1 months (range 2-43). Very good to excellent cosmetic results were observed in 91.8% of patients. Ninety-two percent of patients were satisfied with their cosmetic outcome and said they would choose brachytherapy again over the standard course of external beam RT. Six perioperative complications occurred: two developed bleeding at the time of catheter removal, two had abscesses, one developed a hematoma, and one had a nonhealing sinus tract requiring surgical intervention. Significant fibrosis (moderate-to-severe scarring and thickening of the skin and breast) was noted in only 4 patients; 1 had received 55 Gy and 3 had received 60 Gy. Abnormal posttreatment mammograms were seen in 19 patients. Eight patients underwent rebiopsy for abnormalities found either by mammography or on physical examination; all proved to be fat necrosis or post-RT changes. The rebiopsy rates appeared to correlate with doses >/=55 Gy (6 [75%] of 8 compared with 29 [60%]of 48 overall) and implant volumes >/=128 cm(3) (7 [87.5%] of 8 compared with 36 [75%] of 48 overall). To date, no local, regional, or distant recurrences have been observed. CONCLUSION: Low-dose-rate implants up to 60 Gy were well-tolerated overall. With an implant dose of 60 Gy, the incidence of posttreatment fibrosis (25%) appeared to be increased. Only the long-term follow-up of this and other implant studies will allow an understanding of the total radiation dose necessary for tumor control and the volume of breast that requires treatment.

Adult↗

PubMed2003

Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741.

PURPOSE: Using a 2 x 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. PATIENTS AND METHODS: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A x 4 (doses) --> T x 4 --> C x 4 with doses every 3 weeks, (II) sequential A x 4 --> T x 4 --> C x 4 every 2 weeks with filgrastim, (III) concurrent AC x 4 --> T x 4 every 3 weeks, or (IV) concurrent AC x 4 --> T x 4 every 2 weeks with filgrastim. RESULTS: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P =.010), and OS (RR = 0.69; P =.013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. CONCLUSION: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.

Adult↗

PubMed2003

Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: a pilot study.

PURPOSE: Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast cancer. We conducted a pilot study of preoperative trastuzumab and paclitaxel, followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer. PATIENTS AND METHODS: Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially. RESULTS: Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment. CONCLUSION: Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy.

Adult↗

PubMed2002

Model-based predictions of BRCA1/2 mutation status in breast carcinoma patients treated at an academic medical center.

BACKGROUND: Women with an existing breast carcinoma diagnosis who are found to carry a BRCA1/2 mutation have a substantial risk of developing both a contralateral breast carcinoma and ovarian carcinoma. In a newly diagnosed breast carcinoma patient, this genetic information may influence the management of her disease. To assess the volume of patients who may need genetic services at the time of diagnosis, the authors determined the proportion of women with newly diagnosed breast carcinoma at the study institution who would be eligible for genetic testing. METHODS: Fifty consecutive women with new breast carcinoma who were attending a multidisciplinary clinic were interviewed. Detailed, three-generation pedigrees were collected for each patient by a genetic counselor. Three commonly used probability models were used to calculate each woman's predicted risk of harboring a germline BRCA1/2 mutation. RESULTS: Eleven of 50 patients (22% [95% confidence interval, 12-36%]) were calculated to have a > or = 10% probability of carrying a BRCA1/2 mutation by at least one mathematic model and should have been offered genetic counseling that included the discussion of genetic testing. There were considerable discrepancies between probability calculations among the three mathematic models. One of the 11 patients who was eligible for genetic testing pursued genetic counseling within 12 months of diagnosis. CONCLUSIONS: At a large academic medical center, a substantial proportion of unselected women attending a multidisciplinary clinic were found to have a > or = 10% risk of carrying a BRCA1/2 mutation. The actual number of patients eligible to receive BRCA1/2 genetic testing outweighs the number of patients seen for genetic counseling at the study institution. Finally, limited correlation was found between current predictive models.

Academic Medical Centers↗

PubMed2002

Mammography at a crossroad. How do physicians reconcile conflicting study results with the biologic truths of breast cancer?

The value of routine mammography screening for breast cancer has been the subject of heated debate for much of the last decade. Ten years ago, a baseline mammogram was recommended for women at age 35, and annual mammograms were recommended after age 40. These guidelines were based on the results of mammography trials in Europe and the United States in which a 30% reduction in breast cancer deaths was seen among women who underwent screening.

Adult↗

PubMedDate not supplied

Surgical treatment options in young women with breast cancer.

The diagnosis of breast cancer in young women presents particular challenges in surgical decision making and treatment. These challenges arise from concurrent genetic or other risk factors, potentially more aggressive tumor biology, larger tumor size, and psychosocial factors unique to young women. Local recurrence and survival rates for breast-conserving surgery compared to mastectomy are reviewed and strategies for reducing local recurrence after breast conserving therapy are discussed. Options for incorporating genetic testing and counseling into surgical management are presented. Management of young women with BRCA gene mutations, with a positive family history without a risk gene mutation, and with a history of mantle irradiation for Hodgkin's disease is discussed.

Adult↗