Biomedical subjects

H B Muss

Publications and source records attributed to H B Muss.

At least 19 recordsLinked to original sources

PubMed2000

HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer.

PURPOSE: An association between the overexpression of proto-oncogene HER-2/neu and resistance to tamoxifen in estrogen receptor (ER)-positive primary and metastatic breast cancer has been suggested. We examine a possible interaction between HER-2/neu or p53 expression and tamoxifen effectiveness in patients with ER-positive, node-positive disease treated with cyclophosphamide, doxorubicin, and fluorouracil in a large adjuvant chemotherapy trial (Cancer and Leukemia Group B [CALGB] 8541). Tamoxifen assignment was not randomized-physician discretion was used for premenopausal and postmenopausal women. Trial protocol then specified assignment to postmenopausal women with ER-positive tumors, although not all took tamoxifen. PATIENTS AND METHODS: CALGB 8541 assessed HER-2/neu expression in patients with ER-positive disease by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and amplification by differential polymerase chain reaction (PCR). IHC assessed expression of p53. Univariate and multivariate proportional hazards models assessed tamoxifen-HER-2/neu status interactions and tamoxifen-p53 status interactions. RESULTS: HER-2/neu status was available for 651 patients with ER-positive disease; 650, 608, and 353 patients were assessed by IHC, PCR, and FISH, respectively. Approximately one half received tamoxifen. Reduction in risk of disease recurrence or death resulting from tamoxifen was approximately 37% (32% with overexpression and 39% with normal expression of HER-2/neu; n = 155 by IHC). The tamoxifen-HER-2/neu status interaction was not significant in multivariate analysis of all three HER-2/neu assessment methods. Tamoxifen-p53 interaction did not significantly predict outcome. CONCLUSION: Disease-free and overall survival benefit of tamoxifen in patients with ER-positive, node-positive breast cancer does not depend on HER-2/neu or p53 status. Our data suggest that neither HER-2/neu nor p53 expression should be used to determine assignment of tamoxifen.

Antineoplastic Agents, Hormonal↗

PubMed2000

The association of increased weight, body mass index, and tissue density with the risk of breast carcinoma in Vermont.

BACKGROUND: Etiologic studies of breast carcinoma have indicated that weight, body mass index (BMI), and breast tissue density are important determinants of a woman's risk for the disease. This study looked at the independent effects of these risk factors. METHODS: Data from the Vermont Breast Cancer Surveillance System (VBCSS), collected between May 1996 and November 1997, were used to identify 529 breast carcinoma cases with no prior history of the disease. Each case was matched to four randomly chosen women of the same age who had mammograms during the same time period and had no biopsy-confirmed breast carcinoma. Logistic regression was used to assess the effects of weight, BMI, and breast tissue density on breast carcinoma risk for pre- and postmenopausal women. RESULTS: Weight and BMI were found to be significantly associated with postmenopausal breast carcinoma after adjustment for breast density, and vice versa. The density-adjusted odds ratio for women weighing over 81 kg, relative to women weighing under 63 kg, was 2.1, with a 95% confidence interval (CI) of 1.3-3.2. Relative to women with breasts consisting entirely of fat, the weight-adjusted odds ratios for women with heterogeneously dense and extremely dense breasts were 2.3 (CI: 1.3-4.3) and 4.5 (CI: 1.9-10.6), respectively. CONCLUSIONS: Among postmenopausal Vermont women, weight, BMI, and breast density were independently associated with breast carcinoma risk. Because breast density and weight or BMI are inversely related, estimates of their independent effects should be used when evaluating a woman's risk for breast carcinoma.

Adult↗

PubMed2000

Clinical research in the older cancer patient.

The opportunities for conducting focused research in older patients with cancer continue to increase and reflect the increasing awareness of the incidence of cancer in older persons. As the population ages, cancer will become more and more a problem of the elderly. Despite the magnitude of this problem, exploration of the unique problems associated with cancer in the aging has only begun. Economic issues, access to care, and the frequency of other serious illness in older patients often make screening and treatment of malignancy in older patients a great challenge. Oncologists and geriatricians must work together to guarantee that appropriate funding is made available for cancer research in the elderly population.

Aged↗

PubMed2000

New strategies for managing metastatic breast cancer.

In 1999, metastatic breast cancer claimed the lives of almost 45,000 women. For the vast majority of patients, metastatic breast cancer is an incurable disease with a median survival of only 2 to 3 years after diagnosis. The major goal of therapy is palliation. New endocrine agents developed during the last several years provide a greater opportunity for response in receptor-positive patients. New chemotherapeutic options have led to the reemergence of single-agent therapy as an effective palliative approach. Clinical trials remain the mainstay of cutting-edge therapy for metastatic breast cancer and should always be considered, if available. This review will focus on major issues in the treatment of metastatic breast cancer, including new endocrine and chemotherapeutic agents and a suggested strategy for patient management.

Antibiotics, Antineoplastic↗

PubMed1999

Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741.

PURPOSE: To investigate whether dose escalation of megestrol acetate (MA) improves response rate and survival in comparison with standard doses of MA. PATIENTS AND METHODS: Three hundred sixty-eight patients with metastatic breast cancer, positive and/or unknown estrogen and progesterone receptors, zero or one prior trial of hormonal therapy, and no prior chemotherapy for metastatic disease were prospectively randomized into three groups. The groups of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day). RESULTS: Patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were included in the analyses. The response rates were 23%, 27%, and 27% for the 160-mg, 800-mg, and 1,600-mg arms, respectively. Response duration correlated inversely with dose. Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively. No significant differences in the treatment arms were noted for time to disease progression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The most frequent and troublesome toxicity, weight gain, was dose-related, with approximately 20% of patients on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm. CONCLUSION: With a median follow-up of 8 years, these results demonstrate no advantage for dose escalation of MA in the treatment of metastatic breast cancer.

Adult↗

PubMed1999

American Society of Clinical Oncology 1998 update of recommended breast cancer surveillance guidelines.

OBJECTIVE: To determine an effective, evidence-based, postoperative surveillance strategy for the detection and treatment of recurrent breast cancer. Tests are recommended only if they have an impact on the outcomes specified by American Society of Clinical Oncology (ASCO) for clinical practice guidelines. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOME: Outcomes of interest include overall and disease-free survival, quality of life, toxicity reduction, and secondarily cost-effectiveness. EVIDENCE: A search was performed to determine all relevant articles published over the past 20 years on the efficacy of surveillance testing for breast cancer recurrence. These publications comprised both retrospective and prospective studies. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS, HARMS, AND COSTS: The possible consequences of false-positive and -negative tests were considered in evaluating a preference for one of two tests providing similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The attached guidelines and text summarize the updated recommendations of the ASCO breast cancer expert panel. Data are sufficient to recommend monthly breast self-examination, annual mammography of the preserved and contralateral breast, and a careful history and physical examination every 3 to 6 months for 3 years, then every 6 to 12 months for 2 years, then annually. Data are not sufficient to recommend routine bone scans, chest radiographs, hematologic blood counts, tumor markers (carcinoembryonic antigen, cancer antigen [CA] 15-5, and CA 27.29), liver ultrasonograms, or computed tomography scans. VALIDATION: The recommendations of the breast cancer expert panel were evaluated and supported by the ASCO Health Services Research Committee reviewers and the ASCO Board of Directors.

Breast Neoplasms↗

PubMed1998

erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer.

BACKGROUND: We have previously reported that high expression of the erbB-2 gene (also known as HER-2/neu and ERBB2) in breast cancer is associated with patient response to dose-intensive treatment with cyclophosphamide, doxorubicin (Adriamycin), and 5-flurouracil (CAF) on the basis of short-term follow-up of 397 patients (set A) with axillary lymph node-positive tumors who were enrolled in Cancer and Leukemia Group B (CALGB) protocol 8541. METHODS: To validate those findings, we conducted immunohistochemical analyses of erbB-2 and p53 protein expression in an additional cohort of 595 patients (set B) from CALGB 8541, as well as a molecular analysis of erbB-2 gene amplification in tumors from all patients (sets A and B). Marker data were compared with clinical, histologic, treatment, and outcome data. RESULTS: Updated analyses of data from set A (median follow-up, 10.4 years) showed an even stronger interaction between erbB-2 expression and CAF dose, by use of either immunohistochemical or molecular data. A similar interaction between erbB-2 expression and CAF dose was observed in all 992 patients, analyzed as a single group. However, for set B alone (median follow-up, 8.2 years), results varied with the method of statistical analysis. By use of a proportional hazards model, the erbB-2 expression-CAF dose interaction was not significant for all patients. However, in the subgroups of patients randomly assigned to the high- or the moderate-dose arms, significance was achieved. When patient data were adjusted for differences by use of a prognostic index (to balance an apparent failure of randomization in the low-dose arm), the erbB-2 expression-CAF dose interaction was significant in all patients from the validation set B as well. An interaction was also observed between p53 immunopositivity and CAF dose. CONCLUSIONS: The hypothesis that patients whose breast tumors exhibit high erbB-2 expression benefit from dose-intensive CAF should be further validated before clinical implementation. Interactions between erbB-2 expression, p53 expression, and CAF dose underscore the complexities of predictive markers where multiple interactions may confound the outcome.

Adult↗

PubMed1998

Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B.

BACKGROUND: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. METHODS: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. RESULTS: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. CONCLUSION: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Endocrine therapy in metastatic breast cancer.

Endocrine therapy represents a mainstay of effective, minimally toxic, palliative treatment for metastatic breast cancer. Research focusing on the mechanism of action of endocrine agents will provide new insights leading to new hormonal approaches in breast cancer treatment. Development of new agents, especially the 'pure' antiestrogens, is of great interest. Combining endocrine therapy with biologic agents, especially antiproliferative compounds, may lead to more effective treatment in the adjuvant as well as the advanced setting. Tables 4 and 5 summarize response rates to the different groups of endocrine agents used in metastatic breast cancer and doses of commonly used agents, respectively. At present, tamoxifen is the drug of choice as first-line endocrine therapy for metastatic breast cancer with no or minimal symptoms in premenopausal or postmenopausal women. Second-line therapy usually consists of megace. Aromatase inhibitors may be used as second- or third-line therapy in postmenopausal women. In premenopausal women, LHRH analogues are a reasonable choice. The other hormonal agents may be beneficial as salvage therapy. More effective endocrine approaches are under development.

Adult↗

PubMed1997

Tamoxifen as initial endocrine therapy for metastatic breast cancer: long term follow-up of two Piedmont Oncology Association (POA) trials.

PURPOSE: To examine the outcomes of endocrine naive patients treated with tamoxifen as initial endocrine therapy for metastatic breast cancer. Data were obtained from the long-term follow-up of two previously published randomized trials. PATIENTS AND METHODS: All patients received tamoxifen 20 mg po in a single daily dose. Eligibility required patients to be age > or = 18, performance status 0-3, and estrogen or progesterone receptor positive or unknown. Patients were ineligible if they had any prior endocrine therapy in either the adjuvant or metastatic setting. RESULTS: 156 patients have been followed for a median of 8.3 years. Median age was 61 years, 83% were > or = 50 years, 84% performance status of 0-1, 43% were both ER and PR positive, 33% had prior chemotherapy, 62% had a disease-free interval of > 2 years, and 59% had only one metastatic site. The complete (14%) and partial (6%) response rate for 147 evaluable patients was 20% (95% CI for CR + PR of 14-27%). Multivariate analysis revealed that improved response was related to soft tissue involvement and positive PR status. The majority of patients with soft tissue, nodal or lung metastases had responses noted within three months. Median time to disease progression was 6.7 months. Multivariate analysis revealed that older patients, those with one metastatic site and those with positive PR status had the longest time to progression. Median survival was 27.2 months. Better performance status, fewer metastatic sites and being PR positive were associated with significantly improved survival. CONCLUSION: The patient population in this series is not likely to be studied in future trials because of the wide use of tamoxifen in the adjuvant setting. In a small percentage of patients with metastatic breast cancer, tamoxifen therapy is associated with prolonged remission and survival. Pretreatment characteristics can help identify such patients.

Adult↗

PubMed1997

Cancer chemotherapy in older adults. A tolerability perspective.

The incidence of cancer increases with age. Since the geriatric population is growing, we will be confronted with an increasing number of patients with cancer who are > 65 years of age. The purpose of this review is to address the use of cancer chemotherapy in older persons with respect to its tolerability. We performed a review of the literature using 'Medline' and the bibliographies of pertinent publications. Information about cancer treatment in older adults was extracted with particular attention to chemotherapy-related toxicity in patients aged > 65 years. Comorbid disease, polypharmacy/drug interactions, psychosocial issues and age-related physiological changes are major issues in caring for older patients with cancer. Since older individuals may have a greater number of comorbid illnesses, treatment should be initiated on the basis of physiological rather than chronological age. Comparative studies show that chemotherapy-related toxicity is similar in older and younger patients, with the exception of haematological toxicity, which may be more severe in older patients, and cardiotoxicity, which is more frequent in the elderly. Other evidence suggests that gastrointestinal and neurotoxicities may also be more severe in older individuals. The dosages of chemotherapeutic agents that are primarily renally excreted may require adjustment in older patients. Haematological reserve is decrease in older individuals, and drugs that cause myelosuppression must be used with care. The use of haemopoietic growth factors in geriatric patients is currently being investigated.

Aged↗

PubMed1997

Breast cancer in older women.

More than 50% of breast cancers are diagnosed in women aged 65 years or older, a quickly growing segment of the population. Healthy older women should be offered state-of-the-art screening and treatment for breast cancer, including mammography, surgery, radiation therapy, and adjuvant therapy for early stage tumors. Clinical trials focusing on the role of adjuvant treatment in older women with breast cancer are of chief importance. The optimal treatment for older women with life-threatening, comorbid conditions may be primary treatment with tamoxifen or adjuvant therapy with tamoxifen alone after definitive surgery. Outside the clinical trials setting, metastatic disease should be treated similarly in all age groups.

Aged↗

PubMed1997

Hormonal therapy of breast cancer: state of the art.

Hormonal therapy has an established role in the treatment of women with metastatic breast cancer and also is now a major component of adjuvant systemic therapy for those with early-stage disease. Moreover, recent data suggest that hormonal agents may have a potential use in the prevention of breast cancer in high-risk groups. This article will provide a general overview of the current roles of hormonal therapy and describe future directions that show particular promise.

Antineoplastic Agents, Hormonal↗

PubMed1996

Combination chemotherapy with hydroxyurea, dacarbazine (DTIC), and etoposide in the treatment of uterine leiomyosarcoma: a Gynecologic Oncology Group study.

Advanced or recurrent uterine leiomyosarcomas have traditionally been resistant to most chemotherapeutic regimens. Preliminary reports suggested the combination of hydroxyurea, dacarbazine (DTIC), and etoposide (VP-16) was sufficiently effective to warrant larger trials. In a Phase II trial undertaken by the Gynecologic Oncology Group, 39 patients with advanced or recurrent leiomyosarcoma were treated with 2 g of hydroxyurea, 700 mg/m2 of DTIC, and 300 mg/m2 of VP-16 in divided doses every 4 weeks. Thirty-eight patients were evaluable for response. Two patients experienced complete responses and five had partial responses for a total objective response rate of 18.4% (95% confidence interval: 7.7-34.3%). In general, therapy was well tolerated with moderate toxicity. Six of the seven responders had disease outside the pelvis. The combination of hydroxyurea, DTIC, and VP-16 exhibits moderate activity against uterine leiomyosarcoma.

Adult↗

PubMed1996

Leucovorin and high-dose fluorouracil in metastatic prostate cancer. A phase II trial of the piedmont Oncology Association.

We performed a Phase II trial of oral leucovorin and high-dose fluorouracil (5FU) in hormone refractory patients with metastatic prostate cancer who had not had prior chemotherapy. 5FU was given as a 24-hour infusion at a dosage of 4 g/m2 and oral leucovorin at a dosage of 50 mg every 6 hours for four doses, starting with the infusion of 5FU. Fifteen patients were treated and three were not evaluable for response. There were no complete (CR) or partial responses (PR) in 12 evaluable patients (95% confidence interval for CR+PR of 0 to 26%). Three patients had stable disease and the remainder progressed. Toxicities were generally mild to moderate, but one patient died of sepsis while neutropenic. This dose and schedule of leucovorin and 5FU is not better than single-agent 5FU in patients with metastatic prostate cancer.

Aged↗

PubMed1996

Tamoxifen in postmenopausal women a safety perspective.

Tamoxifen is a synthetic antiestrogen with both agonist and antagonist properties. It is believed to act primarily through binding to estrogen receptors in breast cancer cells, acting as a competitive inhibitor of estrogen. Tamoxifen has a wide range of systemic effects, possibly acting on every estrogen target tissue in the body. Tamoxifen therapy is associated with a significant reduction in the risk of recurrence and death in postmenopausal women with early stage breast cancer. In addition, it has been shown to effectively suppress preclinical breast cancer, as evidenced by the decrease in second primary breast cancers in adjuvant trials. Tamoxifen is also the most widely used endocrine therapy for women with metastatic breast cancer. Tamoxifen, acting predominantly as an estrogen agonist in the liver, has generally favourable effects on serum lipids in postmenopausal women. In addition, tamoxifen has been shown to preserve bone mineral density and may even decrease the risk of osteoporosis in these women. Most patients treated with tamoxifen have minimal adverse effects. Vasomotor symptoms are the most commonly reported events. Less frequently, vaginal discharge or dryness, nausea and depression have been reported. A slight increase in thromboembolic events in postmenopausal women taking tamoxifen has been suggested in some adjuvant trials. Rarely, ocular toxicity and hepatotoxicity are found. The adverse effect of primary importance is the increased incidence of endometrial carcinoma. Several studies indicate that almost all of the tumours are of low histological grade and stage, similar to those seen with exogenous estrogen use. The relative risk of endometrial cancer in women taking tamoxifen is about 2 to 4 times higher than for postmenopausal women not taking tamoxifen. The benefits of tamoxifen outweigh the risks in almost all postmenopausal women with estrogen receptor-positive early stage breast cancer and in all women with metastatic breast cancer. Should tamoxifen prove to be an effective chemopreventive agent for breast cancer, the risks and benefits of treatment will have to be more carefully assessed for this setting.

Aged↗

PubMed1996

Combination cisplatin and carboplatin in advanced squamous cell carcinoma of the head and neck.

Twenty-three patients with advanced squamous cell carcinoma of the head and neck who had received no prior chemotherapy were treated with carboplatin 350 mg/m2 followed by cisplatin 50 mg/m2 every 28 days. Twenty-one of 23 patients were evaluable for response and toxicity. Eight patients (38%) achieved complete response (CR) or partial response (PR) with 2 CR and 6 PR. The overall median survival was 8.4 months (range 19 days-56+ months). The major toxicity was hematological with grade III/IV granulocytopenia in 32% and grade III/IV thrombocytopenia in 32%. There was very little nonhematological toxicity and no nephrotoxicity. There were no therapy-related deaths. The combination carboplatin/cisplatin is tolerable in patients with squamous cell carcinoma of the head and neck, with objective responses in 38%; however, the response rate was not superior to single-agent carboplatin or cisplatin. Further studies with a higher dose of cisplatin should be considered.

Adult↗

PubMed1996

Breast cancer in older women.

By the end of the 20th century, more than 50% of new breast cancer patients will be greater than 65 years old. Until recently, research focused on this older group of women has been minimal. Previous studies have indicated that the elderly are less likely to be screened, and have lesser and frequently inferior treatment. In contrast, the few clinical trials focusing on the elderly suggest that they do as well with surgery, radiation, and standard chemotherapy regimens as their younger counterparts. Comorbidity is, however, more common in older women, and must be factored into treatment and prognosis. The available data indicate that mammography should be used on a yearly to every-other-year basis for screening older women, including those older than 70 years and in fair to good health. Older women should offered breast preservation options and should receive breast radiation following lumpectomy. Tamoxifen may be used as initial therapy for frail women with early to late stage breast cancer, but is inferior to surgery in achieving long-term local control. Adjuvant tamoxifen should be considered for all high-risk node-negative and all node-positive patients regardless of receptor status. Adjuvant chemotherapy is reasonable for high-risk node-negative and node-positive patients in good health and with reasonable life expectancy (>5 years), although clinical trials have not established efficacy for women in this age group. Older women with metastatic breast cancer are good candidates for endocrine therapy. Chemotherapy should be offered to those with progressive disease after endocrine therapy. There are inadequate numbers of older women enrolled in breast cancer clinical trials. Both physicians and patients should explore and define the barriers to clinical trial participation and develop successful interventions to overcome them.

Adult↗