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M Morrow

Publications and source records attributed to M Morrow.

At least 37 records · Page 2Linked to original sources
PubMed2000

Symposium overview: estrogens and antiestrogens in managing the patient with breast cancer.

The prevalence of breast cancer (a hormonally driven neoplasm) in the United States, the potential health benefits of estrogen replacement therapy for postmenopausal women, and the burgeoning research focusing on selective estrogen receptor modulators (SERMs) have resulted in additional complexity in managing breast cancer. In an attempt to clarify existing data, the Society of Surgical Oncology sponsored a symposium entitled "Estrogens and Antiestrogens in Managing the Patient with Breast Cancer" at its 52nd Annual Cancer Symposium. This conference was held in March 1999 and was chaired by Dr. S. Eva Singletary, Professor of Surgery and Chief of the Surgical Breast Section at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. The following is a review of the material presented by the symposium participants.

Age Factors↗
PubMed2000

Phase I and pharmacologic study of the specific matrix metalloproteinase inhibitor BAY 12-9566 on a protracted oral daily dosing schedule in patients with solid malignancies.

PURPOSE: To evaluate the feasibility of administering BAY 12-9566, a matrix metalloproteinase (MMP) inhibitor with relative specificity against MMP-2, MMP-3, and MMP-9, on a protracted oral daily dosing schedule in patients with advanced solid malignancies. The study also sought to determine the principal toxicities of BAY 12-9566, whether plasma BAY 12-9566 steady state concentrations (C(ss)) of biologic relevance could be sustained for prolonged periods, and whether BAY 12-9566 affected plasma concentrations of MMP-2, MMP-9, and tissue inhibitor of MMP-2 (TIMP-2). PATIENTS AND METHODS: Patients with solid malignancies were treated with BAY 12-9566 at daily oral doses ranging from 100 to 1,600 mg. BAY 12-9566 dose schedules included 100 mg once daily, 400 mg once daily, 400 mg twice daily, 400 mg three times daily, 400 mg four times daily, and 800 mg twice daily. Plasma was collected to study the range of BAY 12-9566 C(ss) values achieved, and exploratory studies were performed to assess the effects of BAY 12-9566 on plasma concentrations of MMP-2, MMP-9, and TIMP-2. RESULTS: Twenty-one patients were treated with 47 28-day courses of BAY 12-9566. The most common side effects were headache, nausea, vomiting, abnormalities in hepatic functions, and thrombocytopenia, which were rarely clinically significant. BAY 12-9566 was well tolerated on all dose schedules, and there was no consistent dose-limiting toxicity that precluded treatment in the range of dose schedules evaluated. Instead, dose escalation was terminated because BAY 12-9566 plasma C(ss) values increased less than proportionately and plateaued as the daily dose was increased within the dose range of 100 to 1,600 mg/d, suggesting saturable drug absorption. Mean plasma C(ss) values achieved with all dose schedules exceeded BAY 12-9566 concentrations required to inhibit MMPs in vitro and in vascular invasion and tumor proliferation in vivo models. There were no consistent effects of BAY 12-9566 on the plasma concentrations of MMP-2 and MMP-9 over the continuous dosing period at any dose schedule level. However, plasma levels of TIMP-2 seemed to increase in a dose-dependent manner (r(2) =.50, P =.046). CONCLUSIONS: The recommended dose of BAY 12-9566 for subsequent disease directed studies is 800 mg twice daily, which resulted in biologically relevant plasma C(ss) values and an acceptable toxicity profile. Although exploratory studies of MMPs in plasma were not revealing, it is conceivable that some tumor types and disease settings are more likely to produce more readily quantifiable levels of activated MMPs than others. Therefore, attempts to identify and quantify surrogate markers of MMP inhibitory effects should continue to be performed in disease-directed studies in more homogenous patient populations.

Administration, Oral↗
PubMed1999

Intramolecular and intermolecular geometry of thiophenes with oxygen-containing substituents.

The intramolecular and intermolecular geometries of six thiophenes carrying oxygen-containing substituents have been determined. Crystals of 2-methoxythiophene and 3-methoxythiophene were grown in situ on a diffractometer from liquid samples. The 2-methoxy group introduces significant distortions to the thiophene nucleus and each molecule participates in four S.O contacts leading to an infinite bilayer. The extended structure of 3-methoxythiophene comprises zigzag chains of molecules linked by S.O contacts. Molecules of 2-acetyl-3-methoxythiophene are arranged in pairs about inversion centres, with ring centroids 3.835 Å apart. 5-Cyano-3-hydroxythiophene adopts the hydroxythiophene tautomeric form which allows conjugation between the S atom and the nitrile group: O-H.N hydrogen bonding leads to chains which are cross-linked by S.O contacts to give infinite two-dimensional layers. 5-(Methylthio)thiophen-3(2H)-one exists exclusively as the thiophen-3(2H)-one form in the solid state, allowing maximum conjugative interaction of both the ring heteroatom and the substituent with the carbonyl group: each molecule is linked to two of its neighbours through pairwise C-H.O interactions, forming ribbons. Spiro[cyclohexane-1,2'-2',3'-dihydrothiophen]-3'-one crystallizes with four independent molecules in the asymmetric unit with only minor differences between these: the five- and six-membered rings in each molecule are approximately orthogonal and C-H.O hydrogen bonding generates chains. The last two structures differ from the others in that they lack a fully aromatic thiophene system.

Journal Article↗
PubMed1999

The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation.

CONTEXT: Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. OBJECTIVE: To determine whether women taking raloxifene have a lower risk of invasive breast cancer. DESIGN AND SETTING: The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe. PARTICIPANTS: A total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded. INTERVENTION: Raloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets. MAIN OUTCOME MEASURES: New cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review. RESULTS: Thirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor-positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor-negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7). CONCLUSION: Among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.

Aged↗
PubMed1999

Hormone replacement therapy and risk of breast cancer with a favorable histology: results of the Iowa Women's Health Study.

CONTEXT: Long-term, postmenopausal use of hormone replacement therapy (HRT) appears to increase breast cancer risk. Whether the effect of HRT use on risk of breast cancer varies among histological types of invasive carcinoma is unknown. OBJECTIVE: To determine associations between HRT use and risk of ductal carcinoma in situ (DCIS), invasive carcinoma with favorable histology, and invasive ductal or lobular carcinoma. DESIGN: Prospective cohort study whose participants were followed up continuously for 11 years from January 1986 to December 1996. SETTING AND PARTICIPANTS: Iowa Women's Health Study, a population-based random sample of postmenopausal women aged 55 to 69 years in 1986. A total of 1520 incident breast cancer cases occurred in the at-risk cohort of 37 105 women. MAIN OUTCOME MEASURES: Multivariate-adjusted relative risk (RR) of tumor-specific breast cancers associated with duration of ever, current, or past HRT use. RESULTS: Duration of ever HRT use was associated with risk of invasive carcinoma with a favorable histology, with an RR of 1.81 (95% confidence interval [CI], 1.07-3.07) for those who used HRT 5 or fewer years vs an RR of 2.65 (95% CI, 1.34-5.23) for those who used HRT for more than 5 years (P for trend = .005) after adjustment for age and other breast cancer risk factors. There was no association between ever HRT use and the incidence of DCIS or invasive ductal or lobular carcinoma. Among current hormone users, after adjusting for age and other breast cancer risk factors, the RRs (95% CIs) of invasive carcinoma with a favorable histology were 4.42 (2.00-9.76) and 2.63 (1.18-5.89) for 5 or fewer years of use and for more than 5 years of use, respectively. Risk of invasive ductal or lobular carcinoma was associated with current use (< or =5 years) of HRT with an RR of 1.38 (95% CI, 1.03-1.85). CONCLUSIONS: Exposure to HRT was associated most strongly with an increased risk of invasive breast cancer with a favorable prognosis. These data add important clinical information for assessing the risks and benefits of HRT use.

Aged↗
PubMed1999

Impact of same-day screening mammography availability: results of a controlled clinical trial.

BACKGROUND: We conducted a prospective controlled clinical trial in an urban academic general medicine practice to test the effect of same-day mammography availability on adherence to physicians' screening mammography recommendations. PATIENTS AND METHODS: Participants were a consecutive sample of 920 female patients aged 50 years or older who had received a physician's recommendation for screening mammography at an office visit and had no active breast symptoms, history of breast cancer, or a mammogram within the previous 12 months. Women were assigned to same-day screening mammography availability (intervention group) or usual screening mammography scheduling (control group). MAIN OUTCOME MEASURES: Three-, 6-, and 12-month rates of adherence to physicians' recommendations for screening mammography. RESULT: Twenty-six percent of women in the intervention group obtained a same-day screening mammogram. At 3 months, 58% of the women in the intervention group underwent the recommended screening mammography compared with 43% of the women in the control group (P<.001), increasing to 61% and 49% at 6 months (P<.001), and 268 (66%) of 408 vs 287 (56%) of 512 at 12 months (P = .003). The difference between the intervention and control groups 3-month adherence rates was most marked among women aged 65 years or older (58% vs 34%; P<.001), women who were not employed (54% vs 36%; P<.001), and women with a history of having had either no mammograms (39% vs 20%; P = .02) or only 1 to 2 mammograms (57% vs 38%; P<.001) within the last 5 years. CONCLUSIONS: Same-day mammography availability increased 3-, 6-, and 12-month screening mammography adherence rates in this urban academic general medicine practice. The effect was most marked among women aged 65 years or older, women who were not employed, and those who had had fewer than 3 mammograms in the last 5 years. The efficacy of this intervention in other settings still needs to be demonstrated.

Academic Medical Centers↗
PubMed1999

Identification of the woman at risk for breast cancer: problem solved?

The clinical availability of antiestrogens to reduce breast cancer incidence has focused increased attention on the ability to identify women at increased risk for breast cancer development. Multiple risk factors, which can be grouped under the headings of genetic and familial factors, hormonal factors, benign breast disease, and environmental factors have been described. However, of these risk factors, only genetic mutations and atypical hyperplasia, lobular carcinoma in situ, and ductal carcinoma in situ have a relative risk of four or more. Many of the other risk factors, although associated with statistically significant increases in risk in large populations, are of little practical significance for the individual woman. Lack of knowledge of the interactions among various positive and negative risk factors also complicates the evaluation of risk. In addition, the impact of some risk factors may not be constant over time, and the majority of data on risk come from studies of white women, and little is known about the impact of ethnic diversity on these factors. Finally, there is no consensus about what level of increase in risk is necessary for a women to be labeled "high risk." It is important to recognize that only 50% of breast cancers occur in women with identifiable risk factors other than age. Thus, an improved ability to define risk status is needed if prevention studies directed at high-risk women are to have a major impact on breast cancer incidence and mortality.

Breast Neoplasms↗
PubMed1999

Breast cancer. Making the diagnosis.

The approach to women with breast complaints must be individualized based on the presenting problem, patients' age, and the degree of clinical suspicion. Needle-biopsy, techniques are often cost-effective. In patients with suspicious breast abnormalities, a thorough imaging workup facilitates the selection of definitive local therapy.

Age Factors↗
PubMed1999

Role conflict and rapid socio-economic change: breastfeeding among employed women in Thailand.

Conflicts between women's productive and reproductive roles are intensified by rapid development and social change. Women have a right to offer optimum nutrition to their babies through breastfeeding; they also are entitled to seek gainful employment. For many, furthermore, employment is essential to the economic survival of their families. This article derives from a combined qualitative and quantitative study conducted in Chiang Mai, Thailand. Interviews were carried out with 313 women to investigate the experiences of those who resumed employment within six months after delivery. The findings demonstrate that urban women in the modern workplace face many obstacles in their efforts to maintain lactation while simultaneously undertaking paid work. Current public policies do not address these obstacles effectively, which is of particular concern in today's volatile economic climate.

Adult↗
PubMed1999

Postmastectomy radiation therapy: A surgical perspective.

Controversy exists about whether postmastectomy radiotherapy prolongs survival or is merely of benefit to maintain local control. Surgical series of patients treated by radical or modified radical mastectomy alone show locoregional failure rates ranging from 4% to 26%. The likelihood of involvement of supraclavicular and internal mammary nodal metastases increases as the extent of axillary nodal involvement increases. Adjuvant systemic therapy appears to have limited impact on the incidence of locoregional failure. Untreated nodal disease is a potential source of tumor dissemination and provides a biological rationale for a survival benefit for irradiation.

Breast Neoplasms↗
PubMed1999

Belt worn control system and battery for the percutaneous model of the Jarvik 2000 heart.

A belt worn controller and lithium-ion battery pack have been developed for use with the initial clinical trials of the Jarvik 2000 heart. Patient interface considerations, safety, and simplicity were major design inputs for the system. The controller was developed using all analog technology to avoid difficulties with electromagnetic interference (EMI), to minimize susceptibility to electrostatic discharge, and to avoid the need for software validation. Manual control of pump speed is accomplished by a patient operated knob, according to physician instructions for rest and exercise for each individual patient. The system includes alarms and indicators which show the following: the amount of remaining battery charge, if the battery is low and needs replacement, the power in watts being consumed, if the power consumed is above 15 W, if the pump is running below the selected speed setting, and if the pump stops. The control box, curved to be worn on the belt, is only 2.5 inches high for comfort when sitting. The battery pack, also form fitted for patient comfort, weighs just over 1 1/2 pounds and supplies 65 W-h of energy storage, sufficient to run the device for over 8 h at nominal load.

Computers, Analog↗
PubMed1999

Management of axillary lymph nodes in breast cancer: a national patterns of care study of 17,151 patients.

OBJECTIVE: To determine the rates of axillary lymph node dissection (ALND) and axillary irradiation (AI) in patients with breast cancer and to identify the factors influencing them. SUMMARY BACKGROUND DATA: Routine performance of ALND in the treatment of breast cancer has become controversial. AI has been proposed as an alternative to ALND, and it has been suggested that AI in addition to ALND may decrease local failure in high-risk patients. METHODS: A joint study was conducted by the Commission on Cancer of the American College of Surgeons and the American College of Radiology. A total of 17,151 patients with stage I and II breast cancer treated at 819 institutions in 1994 were studied. RESULTS: A total of 15,992 patients underwent ALND (93%). The mean ages of patients who did and did not undergo ALND were 60.4 and 73.0 years. Univariate analysis demonstrated significantly decreased rates of ALND for women age 70 or older (86% vs. 97%), patients with clinical T1 a tumors (81% vs. 93%), grade I histology (90% vs. 95%), and patients with favorable tumor types (88% vs. 94%). The ALND rate did not vary between palpable and nonpalpable tumors. Multivariate analysis of variables affecting the rate of ALND identified type of surgery, age, tumor size, histology, and payer status as significant. A total of 889 patients received AI. Patients not undergoing ALND were more likely to receive AI (10% vs. 5%). A total of 1.6% of patients with no lymph node metastasis underwent AI, 8.9% of those with one to three positive nodes underwent AI, 24.0% of those with four to nine positive lymph nodes underwent AI, and 29.9% of those with > or = 10 positive lymph nodes underwent AI. Multivariate analysis of variables affecting the proportion of patients who received AI and had undergone ALND identified nodal status and type of surgery as significant. CONCLUSIONS: Axillary lymph node dissection continues to be routinely applied in the treatment of breast cancer, and AI remains underused in patients at high risk for local regional relapse.

Adult↗