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Biomedical subjects

A U Buzdar

Publications and source records attributed to A U Buzdar.

At least 19 recordsLinked to original sources
PubMed1992

Carcinoma of the male breast.

The natural history and current management of carcinoma of the breast in men is reviewed. Articles published from 1942 to 1992 on the natural history, clinical manifestations, diagnosis, and treatment of carcinoma of the breast in men were identified using CANCERLINE and MEDLINE. Carcinoma of the breast affects approximately 1000 men per year in the United States; 300 men per year will die of metastatic disease. The mean age at diagnosis is 59 years. The causes of breast cancer in men are unknown. The most common clinical manifestation of breast cancer in men is a painless, firm subareolar mass or a mass in the upper outer quadrant of the breast. Diagnosis can be confirmed by fine-needle aspiration or surgical biopsy. Infiltrating ductal carcinoma is the predominant histologic type. Treatment is similar to that of women with breast cancer. Men with axillary nodal metastasis should receive adjuvant systemic combination chemotherapy or tamoxifen, or both, after primary surgical treatment. Because most men with carcinoma of the breast have estrogen- and progesterone-receptor-positive tumors, distant metastatic disease should be treated initially with hormonal therapies. The epidemiology, prognostic factors, survival by stage, pattern of metastasis, and response to treatment in men are similar to those in women with breast carcinoma. The data suggest, however, that breast cancers in men are more likely to respond to hormonal manipulation.

Breast Neoplasms↗
PubMed1992

Clinical course of patients with breast cancer with ten or more positive nodes who were treated with doxorubicin-containing adjuvant therapy.

Between 1974 and 1986, 283 patients with ten or more positive nodes were treated in four prospective trials using doxorubicin-containing adjuvant chemotherapy. At a median follow-up of 92 months, 182 patients had had a recurrence, and 158 died. An estimated 41% and 37% were disease-free at 5 and 7 years, respectively. Patients with ten positive nodes had a significantly better disease-free survival than those with more than ten such nodes (P = 0.04). The disease-free survival rate and overall survival rate were not influenced by the estrogen receptor status of the tumor, patient age, or disease stage. Long-term data on a large number of patients treated at this institute showed the natural history of this subgroup of patients. Approximately 30% of patient survived disease-free at 10 years after treatment with the systemic therapies used in these protocols. Newer approaches are needed to alter the prognosis of this subgroup of patients further.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

A randomized trial of two dosage schedules of mitomycin C in advanced breast carcinoma.

For mitomycin C (MMC), an effective agent in the treatment of metastatic breast cancer, the optimal dosing strategy in responding patients must be defined because of the dose-limiting, long-term hematologic toxic effects. Sixty-seven patients received treatment for metastatic breast cancer (MMC 20 mg/m2, intravenously) and then were selected randomly to receive either "standard doses" (SD) (20 mg/m2, intravenously) or "low doses" (LD) (5 mg/m2, intravenously) of MMC every 6 weeks. The primary objective was to show that the LD regimen would result in fewer toxic effects and at least equal disease control. Response rates in the two arms were similar: there were no complete responses and five partial responses (15%) in the SD group and two complete responses and six partial responses (24%) in the LD group (P = 0.332). In the SD and LD groups, median times to progression (11 versus 12 weeks, respectively), response duration (10 versus 6 1/2 weeks, respectively), and survival (26 versus 26 weeks, respectively) were similar. The hematologic toxicity was significantly less in the LD group. Nine patients in the LD group were treated with SD at disease progression, and one complete response was observed. It is concluded that, in this group of patients, administration of MMC in LD, compared with SD, resulted in fewer hematologic toxic effects and similar disease control.

Adult↗
PubMed1992

Complications associated with indwelling catheters.

Between 1983 and 1985, 170 consecutive patients received doxorubicin-containing adjuvant chemotherapy through central venous catheters, and four via a long indwelling catheter in the antecubital fossa. The objective of this retrospective study is to determine the acute and chronic complications associated with indwelling catheters. Ninety-four (56%) patients did not experience any complications. The incidence of acute complications was 2%, which included three pneumothorax. Twenty-nine (17%) patients experienced chronic complications. Of those, 20 (12%) developed infectious complications, and 9 (19%) developed thrombus. In addition, 12 (7%) developed multiple complications, and 32 (19%) patients had other local complications at the catheter site, which included allergic reactions and catheter breakage. Each of these complications was resolved with appropriate treatment. None of the patients died from complications of the indwelling catheter.

Bacterial Infections↗
PubMed1992

Adjuvant therapy with escalating doses of doxorubicin and cyclophosphamide with or without leukocyte alpha-interferon for stage II or III breast cancer.

PURPOSE: A prospective study in breast cancer patients was undertaken to determine whether escalating doses of doxorubicin and cyclophosphamide would result in a higher fraction of patients free of disease, and to evaluate the role of leukocyte alpha-interferon. PATIENTS AND METHODS: Between 1982 and 1986, 319 consecutive patients with stage II or III breast cancer with one or more positive nodes were assigned randomly to receive adjuvant chemotherapy that consisted of escalating doses of doxorubicin and cyclophosphamide in combination with vincristine and prednisone or the same chemotherapy regimen followed by 1 year of leukocyte alpha-interferon. Doxorubicin was administered by 72-hour continuous infusion through a central venous catheter (maximum total cumulative dose, 430 mg/m2). All patients with positive or unknown estrogen receptor status were also given tamoxifen for 1 year. RESULTS: The median follow-up was 71 months (range, 35 to 99 months). Correlation of disease-free survival (DFS) with dose-intensity of cyclophosphamide and doxorubicin showed no improvement in DFS for patients who were able to receive escalated drug doses compared with those who were not. Doxorubicin administered by continuous infusion was associated with a negligible risk of cardiotoxicity in this study despite the administration of higher accumulative doses than in our previous adjuvant therapy studies. The DFS rates of patients who did and those who did not receive leukocyte alpha-interferon were similar. CONCLUSIONS: In this study, there was no real evidence that higher drug dose intensity was associated with longer DFS. Leukocyte alpha-interferon as it was used in this study had no therapeutic value. Doxorubicin administered by infusion was associated with a reduced risk of cardiotoxicity.

Adult↗
PubMed1992

Inflammatory breast cancer: a review.

PURPOSE: The natural history of inflammatory breast cancer and the recent advances in its management were reviewed. DESIGN: The English medical literature from 1924 to 1990 was reviewed using the Cancerline and Medline retrieval systems, and through a manual review of bibliographies of identified articles. RESULTS: The majority of patients with inflammatory breast cancer treated only with local therapies died 18 to 24 months after diagnosis. A combined modality approach with chemotherapy, surgery, and radiation therapy has improved disease-free and overall survival rates for inflammatory breast cancer. Approximately 35% to 55% of patients treated with combined modality regimens remain disease-free and alive at 5 years. CONCLUSION: Induction combination chemotherapy administered with radiation therapy, mastectomy, both, or with additional chemotherapy favorably alters the natural history of inflammatory breast cancer. New drug combinations and high-dose chemotherapy with autologous bone marrow support are being evaluated to improve further patient survival.

Breast Neoplasms↗
PubMed1991

Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer.

Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).

Adult↗
PubMed1991

Phase II evaluation of interferon added to tamoxifen in the treatment of metastatic breast cancer.

This phase II trial evaluated the clinical role of interferon (IFN) in overcoming tamoxifen (TAM) resistance in breast cancer. Twenty women and 1 man received recombinant alpha interferon (5 million units per meter squared intramuscularly, 5 times per week) plus TAM (10 mg orally, twice daily) for the treatment of metastatic breast cancer, either after failing tamoxifen therapy or as frontline hormonal therapy. Of the 9 evaluable patients with disease progression after an objective response to TAM, there were no partial or complete responses with the addition of IFN. Ten evaluable patients received TAM plus IFN as frontline hormonal therapy with 2 complete and 3 partial responses for an overall response rate (RR) of 50% (95% confidence interval = 19-81), a 71% RR for ER-positive patients (95% confidence interval = 29-96) and no responses in ER-unknown patients. Sixteen patients required dose reductions of IFN and 8 patients discontinued therapy due to toxicity. It is unlikely that the RR for TAM plus IFN is greater that than seen with TAM alone, or that the addition of IFN to TAM therapy can overcome clinical TAM resistance.

Breast Neoplasms↗
PubMed1991

Current status of adjuvant therapy of early breast cancer.

Adjuvant therapy in operable breast cancer (stage I and II) can significantly reduce the risk of recurrences and improve survival. In stage I disease, 20-30% of patients will eventually recur. Several prognostic factors may help in identifying poor prognostic subgroups of stage I patients, including ER and PR status, flow cytometry data, nuclear grade, neu oncogene expression, and perhaps haptoglobin-related protein, Cathepsin-D, and Ki-67 expression. Single-agent chemotherapy and oophorectomy have not resulted in prolongation of survival. Combination chemotherapy regimens are superior to single agents, and doxorubicin-containing regimens may be superior to non-doxorubicin-containing regimens. Tamoxifen is effective in improving survival in patients who are ER positive, particularly those women older than 50 years. It appears that six cycles of an effective regimen is as effective as more prolonged administration of the same drugs, and drugs should be given at the optimal dose rate. Preliminary results of alternating non-cross-resistant chemotherapy regimens show promise, but additional data are needed to determine its impact on survival.

Antineoplastic Agents↗
PubMed1991

Recent advances in the treatment of breast cancer.

Multidisciplinary efforts have defined a number of prognostic factors and newer strategies to improve the outcome of patients with breast cancer. Conservative surgery has led to improved functional and cosmetic results. The development of a number of effective adjuvant regimens has led to improved survival. In patients with stage I disease, several biological characteristics of tumor have been identified that are associated with increased risk of relapse. A multimodality approach to patients with locally advanced disease and inflammatory cancer has resulted in improved survival. A number of hormonal and cytotoxic drug contaminations can palliate metastatic disease, with a small fraction of patients remaining in extended remission. Dose-intensive programs may lead to further improvements in survival of selected patients with this disease.

Breast Neoplasms↗
PubMed1991

Indium-111-labeled B72.3 monoclonal antibody in the detection and staging of breast cancer: a phase I study.

Sixteen patients with primary breast cancer were studied with a pancarcinoma monoclonal antibody B72.3, an IgG1 molecule directed against tumor-associated glycoprotein (TAG-72) present in several tumors. Five millicuries of 111In was used to label 0.2 mg (six patients), or 2 mg (six patients), or 20 mg using the site-directed bifunctional DTPA method (at carbohydrate moiety). Digital, planar, and SPECT images were obtained at 2, 48, 72 and 96 hr when possible. HAMA levels were obtained before the Mab infusion and at 1, 3, and 6 wk postinfusion. Fourteen of 14 known primary breast lesions were detected by imaging (100% sensitivity). Two fibrocystic lesions were negative. Seven of 14 patients had lymph node metastases by histologic methods, but all were missed by radioimmunoscintigraphy. Tumor uptake of Mab ranged 0.00054%-0.0038% of the ID/g. The tumor-to-normal breast tissue ratio was 4.3 +/- 0.91 (mean +/- s.e.m.). Lymph nodes localization of 111In-B72.3 by tissue analysis was similar for tumor-bearing and normal nodes (0.0039 +/- 0.0023 versus 0.0025 +/- 0.0019). Pharmacokinetics revealed mean plasma half-life of 33.3-41.2 hr for the different doses. There was no statistical difference between any of the pharmacokinetic parameters of different doses. HAMA was positive only in 17% of the patients. The study suggests that this antibody has 100% sensitivity for primary breast cancers, but very poor detection rate of metastatic lesions in axillary lymph nodes; thus making it of questionable value in the initial staging process of this disease.

Antibodies, Monoclonal↗
PubMed1990

Pregnancy and offspring after adjuvant chemotherapy in breast cancer patients.

A retrospective review of 227 consecutive breast cancer patients who were 35 years of age or younger and who had been given doxorubicin-containing adjuvant chemotherapy was conducted to determine the frequency of pregnancy and its effect on the clinical course of the disease. Also, the status of the newborn was evaluated. There were 33 pregnancies in 25 patients (10 pregnancies were terminated, 2 patients had spontaneous abortions, and 19 patients gave birth to full-term offspring without fetal malformation). Two patients were still pregnant at the time of this report. The median interval between the completion of chemotherapy and pregnancy was 12 months. Eight patients who became pregnant experienced temporary amenorrhea during chemotherapy. Of the 25 patients who became pregnant, recurrent disease subsequently developed in 7 and 3 died. A patient's disease-free and overall survival status was not adversely effected by pregnancy. These data illustrate that in a sizeable fraction of patients 35 years of age or younger treated with adjuvant doxorubicin-containing therapy, ovarian function remained intact and subsequent pregnancy did not affect the disease-free or overall survival of the patients.

Abortion, Incomplete↗
PubMed1990

Is chemotherapy effective in reducing the local failure rate in patients with operable breast cancer?

To evaluate the role of chemotherapy in local control of primary breast cancer, the incidence of local failure was evaluated in 768 patients treated with surgery and adjuvant, combination chemotherapy that contained fluorouracil, doxorubicin, and cyclophosphamide (FAC) at our institute between 1974 and 1982. Of these patients, 429 received postoperative irradiation (XRT) before adjuvant therapy. A group of 178 historical control patients had mastectomies and received irradiation after surgery without chemotherapy. The rates of locoregional recurrence alone in the three groups were as follows: FAC, 12%; FAC plus XRT, 5%; and XRT, 10%. The difference in recurrence rates between the FAC group and the FAC plus XRT subgroup was significant (P less than 0.01). Local failure rates were evaluated by stage and nodal status; patients with Stage III disease and those with four or more disease-positive nodes had a higher incidence of local failure than did patients with Stage II disease or those who had one to three positive nodes. Systemic chemotherapy and local therapies resulted in 50% local control at the time of locoregional recurrence in patients treated with FAC, whereas local control was achieved in 18% of patients with local recurrence in the XRT subgroups. Overall life-time local control of disease was similar whether irradiation was administered initially (in the period after operation) or at the time of local recurrence. Irradiation after mastectomy remains an integral part of a combined modality approach in selected groups of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Acute superior vena caval thrombosis after central venous catheter removal: successful treatment with thrombolytic therapy.

The use of central venous catheters for the administration of cancer chemotherapy has become commonplace, but a variety of potential complications related to catheter use have been clinically recognized. We report a patient in whom acute superior vena cava thrombosis developed after removal of a central venous catheter used to administer chemotherapy for breast cancer. Prompt clinical recognition and therapy resulted in resolution of the thrombus, both clinically and radiographically.

Acute Disease↗