Inclusion of taxanes, particularly weekly paclitaxel, in preoperative chemotherapy improves pathologic complete response rate in estrogen receptor-positive breast cancers.

BACKGROUND: We examined if inclusion of a taxane and more prolonged preoperative chemotherapy improves pathologic complete response (pCR) rate in estrogen receptor (ER)-positive breast cancer compared with three to four courses of 5-fluorouracil, doxorubicin, cyclophosphamide (FAC). PATIENTS AND METHODS: Pooled analysis of results from seven consecutive neo-adjuvant chemotherapy trials including 1079 patients was carried out. These studies were conducted at MD Anderson Cancer Center from 1974 to 2001. Four hundred and twenty-six (39.5%) patients received taxane-based neo-adjuvant therapy. pCR rates and survival times were analyzed as a function of chemotherapy regimen and ER status. Multivariate logistic and Cox regression analysis were carried out to identify variables associated with pCR and survival. RESULTS: Patients with ER-negative cancer had higher overall pCR rate than patients with ER-positive tumors (20.1% versus 4.9%, P < 0.001). In ER-negative patients, the pCR rates were 29% and 15% with and without a taxane (P < 0.001). In ER-positive patients, the pCR rates were 8.8% and 2.0% with and without a taxane (P < 0.001). In multivariate analysis, clinical tumor size (P < 0.001), ER-negative status (P < 0.001) and inclusion of a taxane (P = 0.01) were independently associated with pCR. For patients with pCR, survival was similar regardless of ER status or the type of regimen that induced pCR. CONCLUSION: pCR rates increased for patients with both ER-positive and ER-negative tumors as regimens started to include a taxane and became longer. This indicates that a subset of patients with ER-positive breast cancer benefits from more aggressive chemotherapy, similarly to patients with ER-negative tumors.

Choroid plexus cysts in the mid-trimester fetus--practical application suggests superiority of an individualized risk method of counseling for trisomy 18.

OBJECTIVES: Analysis of a referral population of patients with choroid plexus cysts (CPCs) was performed to compare an average risk method of counseling to an individualized risk method. METHODS: A total of 395 patients referred to a Prenatal Diagnosis Center were included, of whom 341 had isolated CPCs and 54 had associated ultrasound abnormalities. For isolated CPCs, an average risk of 1/150 for aneuploidy was compared to an individualized risk assessment [prior risk as determined by maternal age or serum screening multiplied by the likelihood ratio established by Gupta et al. (1997)]. Accuracy, cost, and procedure-related losses were assessed. RESULTS: Both methods resulted in 100% sensitivity. The individualized method resulted in greater specificity, decreased costs, and (theoretically) fewer procedure-related pregnancy losses. CONCLUSIONS: An individualized risk method of counseling utilizing the likelihood ratios established by Gupta et al. (1997) was superior to an average risk method for assessing trisomy 18 risk in the setting of CPC detected in mid-trimester.

Factors predictive of outcome in patients with breast cancer refractory to neoadjuvant chemotherapy.

PURPOSE: The purpose of this study was to determine the clinical, pathological, and treatment factors that are predictive of local-regional recurrence and overall survival for patients with breast cancer that is refractory to neoadjuvant chemotherapy. PATIENTS AND METHODS: This study analyzed the data of the 177 breast cancer patients treated on our institutional protocols who had less than a partial response to neoadjuvant chemotherapy. The initial clinical stage of disease was II in 27%, III in 69%, and IV (supraclavicular lymph node involvement) in 4%. Surgery was performed in 94% of the patients, and 77% of these patients also received adjuvant chemotherapy. RESULTS: After a median follow-up of 5.2 years, 106 patients experienced disease recurrence, with 98 of these having distant metastases and 45 having local-regional recurrence. The 5- and 10-year overall survivals for the entire group were 56% and 33%, respectively. The factors that were independently associated with a statistically significant poorer overall survival in a Cox regression analysis were pathologically involved lymph nodes after surgery, estrogen receptor-negative disease, and progressive disease during neoadjuvant chemotherapy. The 5-year overall survival for patients with pathologically negative lymph nodes ranged from 84% (estrogen receptor-positive disease) to 75% (estrogen re-ceptor-negative disease), compared with rates for patients with pathologically positive lymph nodes of 66% (estrogen receptor-positive disease) and 40% (estrogen receptor-negative disease). The 5-year survival of patients with progressive disease was only 19%. The 5- and 10-year local-regional recurrence rates for the 177 patients were 27% and 34%, respectively. Significant factors on Cox analysis that predicted for local-regional recurrence were four or more pathologically involved lymph nodes and estrogen receptor-negative disease. For the 105 patients treated with surgery and postoperative radiation therapy, the 10-year local-regional recurrence rates for the subgroups with 0, 1, or 2 of these factors were 12%, 25%, and 44%, respectively. CONCLUSIONS: For patients with a poor response to neoadjuvant chemotherapy, conventional treatments achieve reasonable outcomes in those with lymph node-negative disease or estrogen receptor-positive disease. However, more active systemic and local therapies are needed for patients with estrogen receptor-negative disease and positive lymph nodes and for those with clinical evidence of progressive disease during neoadjuvant chemotherapy.

Traumatic Brain Injury Collaborative Planning Group: a protocol for community intervention.

OBJECTIVE: The Traumatic Brain Injury Collaborative Planning Group was formed in December 1992 to address service gaps and better use agencies and their programs to meet the specialized needs of individuals with traumatic brain injury (TBI). SETTING: The group meetings served as the interagency link between service providers for comprehensive planning and problem solving. OUTCOME MEASURES: This article focuses on the three main tasks of this group: (1) interagency case planning among participating agencies; (2) provision of training and networking opportunities for service providers working with this population; (3) development of creative funding mechanisms for community education and support services to assist individuals to live and work in the community. METHODS: The methods used to organize the collaborative, direct it toward the three main tasks, and maintain it without any agency funding are outlined. RESULTS: Data collected about the 21 persons served in the past 3 years is provided, and protocol forms are shared. CONCLUSION: This model of collaboration throughout a countywide area has been used as a basis for similar development in several other states.

Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: The University of Texas M.D. Anderson Cancer Center experience.

PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy. PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor-positive tumors received tamoxifen for 5 years. RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred. CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.

Combined modality treatment of locally advanced breast carcinoma in elderly patients or patients with severe comorbid conditions using tamoxifen as the primary therapy.

BACKGROUND: The purpose of the current study was to evaluate the objective response rate and possibility of breast-conserving surgery using neoadjuvant tamoxifen in the multimodality treatment, including surgery and radiotherapy, of elderly or frail patients with locally advanced breast carcinoma. METHODS: Forty-seven patients age > 75 years or age < 75 years with comorbid conditions and locally advanced breast carcinoma were treated with neoadjuvant tamoxifen (20 mg/day) for 3-6 months. This was followed by surgery and radiotherapy when feasible and adjuvant tamoxifen for 5 years or until disease recurrence. RESULTS: The median age of the patients was 72 years (range, 48-86 years). Approximately 22% had T3 lesions, 57% had T4 lesions, 22% were Stage II (AJCC Manual for Staging Cancer, 3rd edition), and 78% were Stage III. Eighty percent were estrogen receptor positive. After 6 months of treatment with neoadjuvant tamoxifen, a response rate of 47% was observed, including a complete response rate of 6%. Twenty-nine patients (62%) were rendered free of disease by surgery, including 5 with breast-conserving procedures. After a median follow-up of 40 months, 23 patients (49%) remained disease free. The median survival time had not been reached at the time of last follow-up. No major toxicity was observed, with the exception of one patient who developed a possible tamoxifen-related Stage I endometrial carcinoma. The estimated 2-year and 5-year progression free and overall survival rates were 50% and 41%, and 83% and 59%, respectively. CONCLUSIONS: The results of the current study show that neoadjuvant tamoxifen was effective in the treatment of elderly or frail patients with locally advanced breast carcinoma with estrogen receptor positive tumors, and resulted in a reasonable response rate, including complete responses and good overall survival.

Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma.

BACKGROUND: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. PATIENTS AND METHODS: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. RESULTS: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy. CONCLUSIONS: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.

Acute electrocardiographic changes after pneumonectomy.

BACKGROUND: Postpneumonectomy electrocardiographic (ECG) changes have not been well-defined. METHODS: We reviewed the clinical data and the preoperative and postpneumonectomy ECGs of 15 patients who had pneumonectomy. RESULTS: All postpneumonectomy ECGs showed a higher heart rate and two (13%) showed diffuse ST elevation. Four patients (27%) had transient atrial arrhythmias. Five patients (33%) had some ECG findings of acute cor pulmonale. A leftward shift of the QRS axis occurred after left pneumonectomy. The precordial transitional zone shifted counterclockwise after right pneumonectomy. CONCLUSIONS: Except for one case of septal myocardial infarction, postpneumonectomy ECG changes appeared to result from the pneumonectomy and not from cardiopulmonary disease. Recognition of expected postpneumonectomy ECG findings will help avoid confusing these changes with acute cardiac and pulmonary events, which should reduce patient morbidity and costs.

Phase II study of paclitaxel in patients with metastatic breast carcinoma refractory to standard chemotherapy.

BACKGROUND: The authors conducted a single institution Phase II clinical trial to determine whether paclitaxel had antitumor activity in patients with metastatic breast carcinoma that was refractory to standard chemotherapy. METHODS: Patients with metastatic breast carcinoma were eligible for the study if they had disease progression after at least 2 prior chemotherapy regimens. Patients who had received three prior regimens were treated in a separate cohort. All patients were required to have received doxorubicin in the past and were not eligible if they had received prior therapy with paclitaxel. The starting dose of paclitaxel for low risk patients was 175 mg/m2, administered as a 24-hour continuous infusion; the starting dose of paclitaxel was 150 mg/m2 for patients who had received > or = 3 prior regimens. Therapy was given every 3 weeks and continued for at least 2 courses unless there was evidence of rapidly progressing disease, for at least 3 courses if there was no change in disease and Grade 3 or 4 (based on National Cancer Institute toxicity criteria) toxicity was not noted, and for 6 courses beyond the maximum response in patients who demonstrated complete or partial responses and showed no evidence of disease progression. RESULTS: Sixty-eight of 69 patients entered in the study were evaluable for response: 35 patients who had received 2 prior chemotherapy regimens for Stage IV disease and 33 patients who had received > or =3 prior regimens. A partial response was observed in 7 patients who had received 2 prior regimens, for an objective response rate of 20% (95% confidence interval [95% CI], 14-26%). In the group who had received > or = 3 prior regimens, a total of 6 partial responses were observed, for an objective response rate of 18% (95% CI, 12-23%). The median response duration was 8.2 months (range, 2.7-10.1 months) for the group who had received 2 prior regimens and 5.8 months (range, 2.1-9.5 months) for patients who received > or = 3 prior regimens. Responses were noted in patients with anthracycline-resistant tumors. CONCLUSIONS: Paclitaxel was active in heavily pretreated patients with metastatic breast carcinoma, including anthracycline-resistant breast carcinoma.

Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer.

PURPOSE: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. PATIENTS AND METHODS: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m(2)) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. RESULTS: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. CONCLUSION: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non-cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up.

Paclitaxel by 24-hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: phase I results.

PURPOSE: We and others have demonstrated the antineoplastic efficacy of paclitaxel as a single agent in metastatic breast cancer. We performed this phase I trial to evaluate the combination of paclitaxel with doxorubicin. PATIENTS AND METHODS: Eligible patients had measurable or evaluable metastatic breast cancer for which this was the initial cytotoxic treatment. They may have received adjuvant chemotherapy with other drugs. The study had four parts. In part 1, the patients received paclitaxel by 24-hour infusion followed by doxorubicin by 48-hour infusion. The paclitaxel dose was to be escalated from a starting dose of 125 mg/m2, and the doxorubicin dose was to remain constant at 60 mg/m2 with treatment repeated every three weeks. The results of part 1 prompted part 2 which was a study of the reverse sequence. Part 3 was a formal study of pharmacology and has been reported (J Clin Oncol 14: 2713-21, 1996). In part 4, patients received doxorubicin 50 mg/m2 by bolus followed by paclitaxel 150 mg/m2 by 24-hour infusion for courses 1 and 2. In all subsequent courses doxorubicin was administered by 48-hour infusion. All patients in all four parts of the study had baseline cardiac scans. All patients received standard premedication for paclitaxel. RESULTS: Forty-eight patients were treated in all four parts of the study. In part 1 (10 patients), the maximum tolerated dose (MTD) was paclitaxel 125 mg/m2/24 hours followed by doxorubicin 48 mg/m2/48 hours as defined by dose-limiting mucositis and neutropenic fever which occurred at the starting dose. For part 2 (21 patients), the MTD was doxorubicin 60 mg/m2/48 hours followed by paclitaxel 160 mg/m2/24 hours. In part 4 (seven patients), the MTD was doxorubicin 50 mg/m2/bolus followed by paclitaxel 135 mg/m2/24 hours. In parts 2 and 4, the dose-limiting toxic effect was neutropenia. Of the entire cohort of 48 patients, seven (15%) had a complete response (one persists at five years without intervening therapy), 26 (54%) had a partial response for an objective response rate of 69% (95% confidence interval (95% CI): 54%-81%). The median follow-up of all living patients is 38+ months (range 20+ to 62+); the median response duration is seven months (range 2-33.7+); the median overall survival is 20.5 months (range 5-54+). The median time to progression is 9.6 months (range 1-33.7+ months). Two patients developed congestive heart failure, one at 24 months after her final dose of doxorubicin which amounted to a cumulative lifetime total doxorubicin dose of 870 mg/m2, one after a total of 660 mg/m2. In both, cardiac symptoms were controlled with medications. CONCLUSIONS: The combination of paclitaxel/24 hours with doxorubicin/48 hours is an effective antineoplastic treatment for metastatic breast cancer. However, the incidence of complete response, the median overall survival, and time to progression were not greater than for standard doxorubicin-based combinations. Additionally, a sequence-dependent interaction between paclitaxel and doxorubicin, given in the schedule described here, was defined. Other strategies and schedules should be evaluated to maximize the antineoplastic efficacy of these two potent agents.

Capecitabine: nursing implications of a new oral chemotherapeutic agent.

PURPOSE/OBJECTIVES: To describe the new oral chemotherapeutic agent capecitabine (Xeloda, Roche Laboratories Inc., Nutley, NJ) and key concepts driving its development and to delineate the nursing impact of patient-administered, home-based chemotherapies. DATA SOURCES: Published papers, investigational materials, package inserts, and clinical experience. DATA SYNTHESIS: Capecitabine recently was approved to treat metastatic breast cancer refractory to paclitaxel and anthracycline-containing regimens. Efficacy has been demonstrated. However, although the current regimen is well-tolerated, > or = 40% of patients require dose modification because of grade 2 or greater toxicity, usually hand-foot syndrome or gastrointestinal symptoms. CONCLUSIONS: Capecitabine frees nurses from infusion-related workload, allowing and demanding a new type and level of patient education. Such education emphasizes compliance with the treatment plan and prevention, timely recognition, and management of toxicities. These practice changes also challenge nurses to advocate for reimbursement of educational practices. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses will play more of a central role as use of patient-administered, home-based therapies increases. Nurses must enhance their patient-education and telephone symptom-management skills and help to secure reimbursement for such activities.

Doxorubicin-induced congestive heart failure in elderly patients with metastatic breast cancer, with long-term follow-up: the M.D. Anderson experience.

PURPOSE: Correlation between aging and doxorubicin-induced congestive heart failure in patients with metastatic breast cancer was studied to determine whether doxorubicin-induced congestive heart failure in elderly patients with metastatic breast cancer is a clinically significant issue. METHODS: This was a retrospective study with a median follow-up of 16.8 years. The setting was a comprehensive cancer center in a large city. A group of 682 consecutive patients with metastatic breast cancer presented to The University of Texas M.D. Anderson Cancer Center between 1973 and 1980. All patients received doxorubicin by bolus infusion. Patients in group 1 (n = 538) were aged 50 to 64 years; patients in group 2 (n = 144) were aged 65 years and older. Medical records of all patients were reviewed. Patients who had congestive heart failure were identified and analyzed. The diagnosis of doxorubicin-induced congestive heart failure was made and confirmed by a cardiologist at the time of its development. The main outcome measure was the cumulative probability of developing doxorubicin-induced congestive heart failure in elderly patients with metastatic breast cancer compared to a younger age group. RESULTS: In group 1, 33 patients, and in group 2, 13 patients developed doxorubicin-related congestive heart failure. The cumulative doses of doxorubicin administered to patients with congestive heart failure were 410 mg/m2 (range 150-550 mg/m2) and 400 (range 100-570 mg/m2), respectively. The time interval from the last date of doxorubicin treatment to the development of congestive heart failure was, respectively, 5 months (range < 1-65 months) and 9 months (range < 1-28 months). There was no statistically significant difference between the two congestive heart failure subgroups, nor were we able to identify risk factors that could have increased the risk of congestive heart failure among these patients. CONCLUSION: Older patients with metastatic breast cancer and no significant comorbidity can be treated with doxorubicin-based chemotherapy with no added risk of developing congestive heart failure beyond that in the younger age group.

Diode verification of routine electron-beam treatments.

A platinum doped n type commercial silicon electron diode/electrometer system was evaluated for use in our comprehensive external beam radiotherapy quality assurance program. Directional dependence of diode response was investigated by positioning the diode at the radiation isocenter and recording the response versus beam incident direction. Dose rate response was examined by testing for nonidealities in inverse square law behavior. Energy dependence of response was explored using 6-21 MeV beams. Dose response linearity was investigated from 50-800 cGy. Radiation perturbation was measured using localization film. Finally, the system was evaluated for initial treatment quality assurance in a number of clinical cases (N = 34). The diode response exhibited +/- 5% variation within +/- 20 degrees of the detector's marked "preferred" direction for the 6 MeV beam. Higher energy electron beams exhibited much less directional dependence. Dose rate response was found constant from 178-326 cGy/min (or 96-130 cm SSD). Energy dependence of response was constant within +/- 5.5% from 6-21 MeV. Dose response was linear (r2 = 0.999). Radiation field perturbation was significant at the depth of dose maximum (dmax). The maximum perturbation measured was -12.5% at dmax using the 6 MeV beam. Clinical trials of the system demonstrated that the diodes could be utilized for initial treatment quality assurance. The system proved effective for routine initial treatment electron beam in vivo dosimetry when the directional and energy dependent limitations of the system were respected.

Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference.

BACKGROUND: The authors report results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with doxorubicin-containing combination chemotherapy at a single institution; this report is meant to serve as a reliable reference for single-arm studies of newer therapies in this patient population. METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast carcinoma were evaluated. RESULTS: The response rate was 65.0% (95% confidence interval [CI]: 62.5-67.3%), complete response (CR) rate was 16.6% (95% CI: 14.8-18.6%), and partial response (PR) rate was 48.5% (95% CI: 46.0-50.9%). Median progression free survival (PFS) was 11.5 months (95% CI: 10.9-12.3 months) and median overall survival (OS) was 21.3 months (95% CI: 20.3-22.7 months). Survival correlated with response to therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the patients who achieved CR (n=263) and 14 and 24.6 months, respectively, for PR patients (n=766). The median OS of patients who had progressive disease during chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number of organs involved and especially with tumor burden. Patients with hormone receptor-positive tumors had a similar response rate to that of patients with hormone receptor negative tumors but had significantly longer PFS (medians of 14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months, respectively). CONCLUSIONS: In patients with metastatic breast carcinoma, doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of 16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all responders and 22.4 months and 41.8 months, respectively, for those who had CR.

Clinical course of breast cancer patients with metastases confined to the lungs treated with chemotherapy. The University of Texas M.D. Anderson Cancer Center experience and review of the literature.

PURPOSE: To evaluate the clinical course of patients with a metastatic breast cancer (MBC) confined to the lungs and treated with doxorubicin/cyclophosphamide-containing chemotherapy (DC-CT). PATIENTS AND METHODS: Between 1973 and 1985, 1581 patients with MBC were treated with DC-CT at M.D. Anderson Cancer Center. Data for 88 patients (5.6%) with metastases confined to the lungs were reviewed to correlate various clinical characteristics with response to treatment and survival. RESULTS: The overall response rate was 76% with 33% achieving complete response (CR). The median overall survival time was 22 months (range 1-210). The 10-year survival rate was 9%. The overall response and CR rates were higher for the patients with metastases confined to the lungs (76% and 33%. respectively) than for the remainder of MBC patients (64% and 14%; P < 0.01). The 10-year survival rate was also higher (9% versus 3%, P < 0.01), but there were no differences in median overall survival rate. CONCLUSIONS: This retrospective analysis demonstrated that patients with metastases confined to the lungs treated with DC-CT had a high objective response rate, especially high CR rates, and a median survival comparable to that of our entire population of MBC patients. A small but clinically significant percentage of patients had prolonged survival. Therefore, not all visceral sites are indicators of poor prognosis.

Acanthosis Nigricans as an early clinical proxy marker of increased risk of type II diabetes.

Diabetes affects 6% of the national population, yet approximately 50% of persons with diabetes remain undiagnosed and receive no treatment. In specific populations, Acanthosis Nigricans (AN) may serve as an early clinical proxy marker of increased risk of type II diabetes. The results of this pilot project to screen selected school age students in New Mexico for AN indicate that a large number of these students may be at increased risk for developing type II diabetes as young adults. The future burden of diabetes on individuals, families, communities, and health care systems may be greater than previously recognized.

The prognostic significance of sialyl-Tn antigen in women treated with breast carcinoma treated with adjuvant chemotherapy.

BACKGROUND: Sialyl-Tn (STn) represents an aberrantly glycosylated mucin epitope that is expressed in breast carcinoma and other adenocarcinomas and is an important factor in the development of novel immunotherapeutic approaches. The primary aim of the current study was to investigate the influence of STn expression on the prognoses of patients with breast carcinoma. METHODS: A cohort of 207 women diagnosed with invasive breast carcinoma who were treated with anthracycline-containing adjuvant chemotherapy and were enrolled in a randomized clinical trial were studied. Expression of STn was determined by an immunohistochemical procedure in which the B72.3 monoclonal antibody was used. Kaplan-Meier and Cox proportional regression survival analyses were used to compare low STn and high STn patients. RESULTS: Forty-eight (23%) of the 207 specimens demonstrated high STn staining (>25% cells were immunoreactive). During a median follow-up of 5 years, high STn patients had worse disease free survival than low STn patients (55% vs. 74%, respectively; P = 0.03). High STn expression was significantly associated with age (P = 0.04) but not with other conventional prognostic markers. In multivariate analysis using the Cox regression model, high STn emerged as an independent prognostic indicator for disease free survival (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.09-3.73) and for overall survival (HR, 2.16; 95% CI, 0.95-4.92). CONCLUSIONS: The results of this study suggest that STn may be a valuable marker for identifying women at high risk of developing recurrent breast carcinoma who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.

Phase I/II study of dose-intense doxorubicin/paclitaxel/cyclophosphamide with peripheral blood progenitor cells and cytokine support in patients with metastatic breast cancer.

Relapse following complete remission achieved with a single course of high-dose chemotherapy continues to be the main cause of treatment failure in patients with metastatic breast cancer. A phase I/II trial was initiated that combined the two most active drugs against breast cancer, doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with cyclophosphamide, and delivered four cycles of these drugs with peripheral blood progenitor cells (PBPCs) and granulocyte colony-stimulating factor support in an outpatient setting. Patients with untreated metastatic breast cancer received two cycles of doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2. During recovery from the second cycle, PBPCs were harvested. Responding patients were then admitted for a day to receive escalating-dose doxorubicin, paclitaxel, and cyclophosphamide followed by PBPC reinfusion on day 3 as outpatients. Seventeen patients have been enrolled to date. Ten patients completed treatment and received 34 cycles of high-dose chemotherapy every 21 days (range, 21 to 28 days). The median age was 47 years (range, 26 to 56 years) and the median number of metastatic sites was two (range, one to three). Five patients had received adjuvant chemotherapy (four cyclophosphamide/methotrexate/5-fluorouracil and one mitoxantrone-based). The most common toxic reactions were nausea and vomiting (75% of courses) and neurosensory (50% of courses). No patients had a decreased ejection fraction or overt congestive heart failure. Ten patients underwent cardiac biopsy (median doxorubicin, 253 mg/m2; range, 120 to 312 mg/m2); only one showed grade 1 cytotoxic changes with doxorubicin 240 mg/ m2. Six patients were admitted for neutropenic fever. Eight of 10 patients responded (two pathologically confirmed complete remissions in liver). At these doses, four cycles of doxorubicin, paclitaxel, and cyclophosphamide with PBPC and granulocyte colony-stimulating factor support every 21 days was well tolerated and showed evidence of activity. Enrollment at higher dose levels continues so that maximum tolerated dose can be defined.