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Biomedical subjects

M Morrow

Publications and source records attributed to M Morrow.

At least 19 recordsLinked to original sources
PubMed2006

A phase I safety, pharmacological and biological study of the farnesyl protein transferase inhibitor, tipifarnib and capecitabine in advanced solid tumors.

BACKGROUND: To evaluate the toxicity and pharmacological and biological properties of the farnesyl protein transferase (FPTase) inhibitor, tipifarnib (R115777, ZARNESTRAtrade mark) and capecitabine administered for 14 days every 3 weeks. PATIENTS AND METHODS: Patients with advanced cancers received twice daily tipifarnib (100-500 mg) and capecitabine (1000-1125 mg/m(2)) for 14 days every 3 weeks. Pharmacokinetics of tipifarnib, capecitabine and 5-fluorouracil (5-FU) were determined. Peripheral blood mononuclear cells were analyzed for farnesylation of the HDJ2 chaperone protein and FPTase activity. RESULTS: Forty-one patients received 185 courses of treatment. Diarrhea and palmar-plantar erythrodysesthesia were dose limiting at 300 mg tipifarnib/1125 mg/m(2) capecitabine b.i.d. When the capecitabine dose was fixed at 1000 mg/m(2) b.i.d., neutropenia was dose limiting at 400 and 500 mg b.i.d. of tipifarnib. Capecitabine did not affect the pharmacology of tipifarnib at 100-300 mg b.i.d., although tipifarnib significantly increased the C(max) of 5-FU at 400 mg b.i.d. HDJ2 farnesylation and FPTase activity decreased between 200 and 400 mg b.i.d. doses of tipifarnib, without a dose-response relationship. Five patients demonstrated partial remissions and 11 patients maintained prolonged stable disease. CONCLUSIONS: Tipifarnib and capecitabine are well tolerated at 300 mg/1000 mg/m(2) b.i.d., respectively, resulting in biologically relevant plasma concentrations and antitumor activity. The recommended dose for further disease-focused studies is 300 mg b.i.d. tipifarnib and 1000 mg/m(2) b.i.d. capecitabine, given for 14 days every 3 weeks.

Adult↗
PubMed2004

Prediction of breast cancer size by ultrasound, mammography and core biopsy.

Neoadjuvant chemotherapy and non-surgical tumor ablation rely upon imaging studies to determine tumor size. In this study the accuracy of ultrasound (US) mammography and core biopsy in determining tumor size was examined in 202 patients with Stages I and II breast cancer. The most accurate single modality for determining tumor size was mammography with a correlation coefficient of 0.66, followed by US (r = 0.48) and core biopsy (r = 0.28). Size measurements were less accurate in lobular than ductal cancers. The combination of the three modalities understaged 25% of the tumors > 1cm in size, and overstaged 10% of those < 1cm. The inability to accurately determine tumor size has important implications for the use of non-surgical ablation.

Adult↗
PubMed2003

Elevated protein kinase C alpha expression may be predictive of tamoxifen treatment failure.

We previously reported that stable transfection of protein kinase C alpha (PKCalpha) into T47D human breast cancer cells results in tamoxifen (TAM)-resistant tumour growth. Relevance of PKCalpha expression in clinical specimens was determined by comparing PKCalpha expression in tumours from patients exhibiting disease recurrence with patients remaining disease-free following TAM treatment. Our results suggest that PKCalpha expression may predict TAM treatment failure.

Adult↗
PubMed2003

Low incidence of CMV viremia and disease after allogeneic peripheral blood stem cell transplantation. Role of pretransplant ganciclovir and post-transplant acyclovir.

To establish the incidence of CMV viremia after allogeneic blood stem cell transplantation, we studied 51 consecutive allogeneic peripheral blood stem cell (PBSC) transplant recipients. A total of 12 recipients were at moderate risk for CMV disease and 39 were at high risk. Conditioning regimens varied, but GvHD prophylaxis consisted of tacrolimus and mini-methotrexate in all patients. All patients received prophylactic ganciclovir from admission until day -2 and prophylactic acyclovir from day -1 until day 180 after transplantation. CMV viremia was treated with ganciclovir. Using a PCR-based technique, the cumulative incidence of CMV viremia was 31+/-14% by day 100 and 35+/-14% by day 150. Donor type, CMV risk group, underlying disorder, conditioning regimen, GvHD, and steroid use were not associated with the risk for CMV viremia. No cases of CMV disease occurred. We hypothesize that the low rate of CMV viremia and the absence of CMV disease in this cohort of PBSCT transplant recipients, which contrasts with other reports, may be related to the prophylactic use of high-dose acyclovir and possibly to pretransplant use of ganciclovir.

Acyclovir↗
PubMed2003

Sentinel lymph node biopsy: benefits and limitations.

Multiple studies have demonstrated that a sentinel node can be identified in most women with breast cancer, and that it reliably predicts the status of the remaining axillary nodes. Contraindications to the procedure are decreasing with experience but further long term follow up is needed.

Breast Neoplasms↗
PubMed2001

Selective estrogen receptor modulation and reduction in risk of breast cancer, osteoporosis, and coronary heart disease.

The recognition of selective estrogen receptor modulation in the laboratory has resulted in the development of two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, for clinical application in healthy women. SERMs are antiestrogenic in the breast but estrogen-like in the bones and reduce circulating cholesterol levels. SERMs also have different degrees of estrogenicity in the uterus. Tamoxifen is used specifically to reduce the incidence of breast cancer in premenopausal and postmenopausal women at risk for the disease. In contrast, raloxifene is used specifically to reduce the risk of osteoporosis in postmenopausal women at high risk for osteoporosis. The study of tamoxifen and raloxifene (STAR) trial is currently comparing the ability of these SERMs to reduce breast cancer incidence in high-risk postmenopausal women. There is intense interest in understanding the molecular mechanism(s) of action of SERMs at target sites in a woman's body. An understanding of the targeted actions of this novel drug group will potentially result in the introduction of new multifunctional medicines with applications as preventive agents or treatments of breast cancer and endometrial cancer, coronary heart disease, and osteoporosis.

Adult↗
PubMed2001

Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma.

PURPOSE: To define patterns of care for the local therapy of stage I and II breast cancer and to identify factors used to select patients for breast-conserving therapy (BCT). PATIENTS AND METHODS: A convenience sample of 16,643 patients with stage I and II breast cancer treated in 1994 was obtained from hospital-based tumor registries. Histologic variables were determined from original pathology reports. RESULTS: BCT was performed in 42.6% of patients. Multivariate analysis demonstrated that living in the Northeast United States (odds ratio [OR], 2.48; 95% confidence interval [CI], 2.16 to 2.84), having a clinical T1 tumor (OR, 2.51; 95% CI, 2.27 to 2.78), and having a tumor without an extensive intraductal component (OR, 2.07; 95% CI, 1.81 to 2.37) were the strongest predictors of breast-conserving surgery. Radiation therapy was given to 86% of patients who had breast-conserving surgery. Age less than 70 years was the most significant predictor of receiving radiation (OR, 2.11; 95% CI, 1.77 to 2.25). Tumor variables did not correlate with the use of radiation, but favorable tumor characteristics were associated with the use of breast-conserving surgery. CONCLUSION: Despite strong evidence supporting the use of BCT, the majority of women continue to be treated with mastectomy. Predictors of the use of BCT do not correspond to those suggested in guidelines.

Adult↗
PubMed2001

Factors influencing the use of breast reconstruction postmastectomy: a National Cancer Database study.

BACKGROUND: Advances in surgical techniques and changes in our understanding of the biology of breast cancer have made immediate or early breast reconstruction a viable option for the majority of women with breast cancer. Little is known about national patterns of use of reconstruction. This study was undertaken to determine national patterns of care and factors that influence the use of breast reconstruction. STUDY DESIGN: A large convenience sample reported to the National Cancer Data Base was studied. Patients coded as undergoing mastectomy between 1985 and 1990 (n = 155,463) and between 1994 and 1995 (n = 68,348) were evaluated. The use of reconstruction in the two time periods was compared, and patient and tumor factors influencing the use of the procedure were compared. RESULTS: Between 1985 and 1990, 3.4% of mastectomy patients had early or immediate reconstruction, increasing to 8.3% in 1994-5. Patient age, income, geographic location, type of hospital where treatment occurred, and tumor stage all influenced the use of reconstruction in univariate analysis. In multivariate analysis, patients age 50 or under had a 4.3-fold greater likelihood of having reconstruction than their older counterparts. Patients with ductal carcinoma in situ were twice as likely as those with invasive cancer to have reconstruction. Family income of $40,000 or more (Odds Ratio 2.0), ethnicity other than African-American (Odds Ratio 1.6), surgery in a National Cancer Institute-designated cancer center (Odds Ratio 1.4), and surgery in a geographic region other than the Midwest or South (Odds Ratio 1.3) remained significant predictors of the use of reconstruction in multivariate analysis. CONCLUSIONS: Breast reconstruction is an underused option in breast cancer management. Predictors of the use of reconstruction do not reflect contraindications to the procedure, and indicate the need for both physician and patient education.

Adult↗
PubMed2001

Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation.

Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.

Aged↗
PubMed2001

Who should not receive chemotherapy? Data from American databases and trials.

The demonstration of the effectiveness of chemotherapy in both premenopausal and postmenopausal women, regardless of estrogen receptor (ER) status, raises the question of whether all breast cancer patients should receive chemotherapy. Several patient groups with such a favorable long-term prognosis that they will obtain an extremely small benefit from chemotherapy can be identified. They include patients with lymph node-negative tumors of 1 cm or less in size, those with grade 1 tumors between 1.1 and 2.0 cm in size, and those with tumors of favorable histologic type (tubular and mucinous) up to 3 cm in size. A patient subgroup in which it is not clear that the benefits of chemotherapy routinely exceed the risks is postmenopausal women with ER-positive, lymph node-negative cancers receiving tamoxifen. There is a wide variation in prognosis in this group, and chemotherapy should be reserved for those at high risk of recurrence. Finally, no benefit for chemotherapy in women aged 70 years and older has been identified. The high rate of death from causes other than breast cancer may negate small survival benefits, and after adjustment for quality of life, the duration of treatment exceeds the gain in life expectancy.

Aged↗
PubMed2001

Prospective comparison of stereotactic core biopsy and surgical excision as diagnostic procedures for breast cancer patients.

OBJECTIVE: To determine whether stereotactic core biopsy (SCNB) is the diagnostic method of choice for all mammographic abnormalities requiring tissue sampling. SUMMARY BACKGROUND DATA: Stereotactic core needle biopsy decreases the cost of diagnosis, but its impact on the number of surgical procedures needed to complete local therapy has not been studied in a large, unselected patient population. METHODS: A total of 1,852 mammographic abnormalities in 1,550 consecutive patients were prospectively categorized for level of cancer risk and underwent SCNB or diagnostic needle localization and surgical excision. Diagnosis, type of cancer surgery, and number of surgical procedures to complete local therapy were obtained from surgical and pathology databases. RESULTS: The malignancy rate was 24%. Surgical biopsy patients were older, more likely to have cancer, and more likely to be treated with breast-conserving therapy than those in the SCNB group. For all types of lesions, regardless of degree of suspicion, patients diagnosed by SCNB were almost three times more likely to have one surgical procedure. However, for patients treated with lumpectomy alone, the number of surgical procedures and the rate of negative margins did not differ between groups. CONCLUSIONS: Stereotactic core needle biopsy is the diagnostic procedure of choice for most mammographic abnormalities. However, for patients undergoing lumpectomy without axillary surgery, it is an extra invasive procedure that does not facilitate obtaining negative margins.

Biopsy, Needle↗
PubMed2001

The surgeon's role in breast cancer chemoprevention.

An individual woman's level of risk for the development of invasive breast cancer can be accurately estimated using the Gail model. This model is not appropriate for use in women with prior breast cancer (invasive or in situ) or a family history suggestive of a genetic predisposition. Tamoxifen is an option for breast cancer risk reduction. The magnitude of benefit varies based on the factors that increase a woman's level of risk, but benefit has been seen in all risk subgroups that have been studied. The risks associated with tamoxifen for prevention vary with menopausal status. In premenopausal women, there are no life threatening toxicities, and quality-of-life issues predominate. In postmenopausal women, the increased risk of endometrial cancer and venous thrombosis mandate a careful assessment of the presence of other risk factors for these conditions prior to considering tamoxifen for prevention. At present, prevention options for the high-risk woman include surveillance, tamoxifen for five years, participation in the STAR trial (if postmenopausal), and bilateral prophylactic mastectomy.

Journal Article↗
PubMed2001

Is axillary dissection necessary after positive sentinel node biopsy? Yes!

Axillary dissection has been considered a staging procedure in recent years. Sentinel node biopsy can accurately stage a patient as node-positive or node-negative, raising questions about the need for completion dissection when the sentinel node is positive. This article summarizes data indicating that approximately 50% of patients with sentinel node metastasis have additional positive nodes. For these women, completion axillary dissection provides prognostic information, maintains local control, and may have a survival benefit. Until definitive data from the American College of Surgeons Z11 study is available, completion dissection should remain standard practice.

Axilla↗
PubMed2000

The evaluation of common breast problems.

The most common breast problems for which women consult a physician are breast pain, nipple discharge and a palpable mass. Most women with these complaints have benign breast disease. Breast pain alone is rarely a presenting symptom of cancer, and imaging studies should be reserved for use in women who fall within usual screening guidelines. A nipple discharge can be characterized as physiologic or pathologic based on the findings of the history and physical examination. A pathologic discharge is an indication for terminal duct excision. A dominant breast mass requires histologic diagnosis. A breast cyst can be diagnosed and treated by aspiration. The management of a solid mass depends on the degree of clinical suspicion and the patient's age.

Algorithms↗
PubMed2000

National Cancer Data Base survey of breast cancer management for patients from low income zip codes.

BACKGROUND: The National Cancer Data Base (NCDB), a joint project of the American College of Surgeons Commission on Cancer and the American Cancer Society, is a cancer management and outcomes data base for health care organizations. It provides a comparative summary of patient care that is used by participating hospitals and communities for self-assessment. The most current (1995-1996) breast cancer data on patients from low income zip codes are described here. METHODS: Since 1989, eight Calls for Data have been issued, yielding a total of 191,714 reports of non-Hispanic white patients with breast cancer for the years analyzed, 1995-1996. A total of 1961 hospital cancer registries have participated in at least one of the Calls for Data. RESULTS: A diverse range of breast cancer cases was reported from a variety of geographic locations and medical care environments. There were general similarities in the treatment of patients from the different income groups; however, some differences were reported. Among patients from lower income zip codes, 60.7% were age 60 years or older, compared with 55.1% from other income zip code groups. The AJCC stage distribution was reported as less favorable for patients from low income zip codes than for other patients. The percentage of patients from low income zip codes diagnosed as Stage 0 or I was 51.2%, compared with 55.9% of patients from the other income zip codes. Of patients from lower income zip codes, 12.1% were reported to have Stage III or IV disease, compared with 10.0% of patients from other income zip codes. Patients from low income zip codes received less tissue-sparing surgery. Of patients from low income zip codes, 14.9% received partial mastectomy with or without radiation or systemic therapy, compared with 18.3% of patients from other income zip codes. The percentage of patients from low income zip codes who received a partial mastectomy with axillary lymph node dissection was 23.3% for patients from other income zip codes, the percentage was 30.5%. Conversely, 49.8% of patients from lower income zip codes received a modified radical mastectomy, compared with 40.5% of patients from other income zip codes. CONCLUSIONS: Further improvements in the early diagnosis and surgical treatment of low income patients can probably be achieved. Programmatic activities that further explain or reduce the apparent nonpreferred treatment of some low income patients should be encouraged.

Adult↗