Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer

We conducted a 2-year, randomized, double-blind, placebo-controlled toxicity trial of therapy with tamoxifen (10 mg twice a day) in 140 postmenopausal women with a history of breast cancer and histologically negative axillary lymph nodes. These women had been treated with surgery with or without radiotherapy. At a 3-month evaluation, tamoxifen-treated women showed a significant decrease in fasting plasma levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, which persisted at 6- and 12-month evaluations. During the first 12 months, plasma triglyceride levels increased; small but significant decreases in high-density lipoprotein cholesterol (HDL) were observed in tamoxifen-treated women, but ratios of total cholesterol to HDL cholesterol and of LDL to HDL cholesterol changed favorably. While data relating lipid/lipoprotein profiles and cardiovascular disease are limited in women, current evidence suggests that total cholesterol and possibly low-density lipoprotein cholesterol are risk factors. We conclude that during the first 12 months of treatment, tamoxifen exerts a favorable effect on the lipid profile in postmenopausal women with early stage breast cancer.     

Effects of tamoxifen on serum lipid and apolipoprotein levels in postmenopausal patients with breast cancer

Serum lipids and apolipoprotein levels were measured in twenty postmenopausal women with primary breast cancer, before and three months after tamoxifen therapy (10 mg twice a day). Tamoxifen caused a significant reduction in total serum cholesterol (10%;P < 0.02), and in low-density lipoprotein cholesterol (17%;P < 0.01), and a significant 47 % increase in the subclass 2 of the high density lipoprotein cholesterol (P< 0.01). In addition, tamoxifen caused a 16% increase in apolipoprotein A-I, a 12% decrease in apolipoprotein B (P < 0.05), and a 37% reduction in the serum concentration of lipoprotein(a) (P< 0.01). These results show that tamoxifen brings about an important improvement in serum lipid profile.     

Tamoxifen treatment reverses the adverse effects of chemotherapy-induced ovarian failure on serum lipids

In all, 146 premenopausal women with early stage breast cancer were treated with adjuvant chemotherapy. In addition, 5-year tamoxifen treatment was started after chemotherapy to those 112 patients with hormone-receptor-positive tumours while those with hormone-receptor-negative tumours received no further therapy. The serum lipid levels were followed in both groups. The levels of serum total and low-density lipoprotein (LDL) cholesterol increased significantly after chemotherapy only in patients who developed ovarian dysfunction. Total cholesterol increased +9.5% and LDL cholesterol +16.6% in patients who developed amenorrhoea (P<0.00001 and 0.00001, respectively). The cholesterol levels did not change in patients who preserved regular menstruation after chemotherapy. After 6 months of tamoxifen therapy, the total cholesterol decreased -9.7% and the LDL cholesterol -16.7% from levels after the chemotherapy, while the cholesterol concentrations remained at increased levels in the control group (P=0.001 and P<0.0001, respectively). The high-density lipoprotein cholesterol levels did not change significantly in either tamoxifen or control group. The effects of tamoxifen treatment on serum lipids after chemotherapy have not been studied before. Our current study suggests that adjuvant tamoxifen therapy reverses the adverse effects of chemotherapy-induced ovarian failure on total and LDL cholesterol and even lowers their serum levels below the baseline.     

Exemestane after tamoxifen as adjuvant hormonal therapy in postmenopausal women with breast cancer: effects on body composition and lipids

Recent studies have shown that administering the aromatase inhibitor exemestane after 2-3 years of tamoxifen therapy significantly improves disease-free survival in postmenopausal women with primary breast cancer in comparison with standard 5-year tamoxifen treatment. Although many of the adverse effects associated with exemestane and tamoxifen have been analysed, there are no comparative data concerning body weight and body composition. The aim of this randomised study was to evaluate the longitudinal changes in body composition and lipid profiles in postmenopausal women switched from tamoxifen to exemestane. In total, 60 overweight or obese postmenopausal patients were enrolled. Their anthropometric data, body composition, including fat mass (FM) and fat-free mass (FFM), and lipid profiles, caloric intake and physical activity were assessed 1 week before randomisation, and 6 and 12 months later. In all, 55 patients (27 on tamoxifen and 28 on exemestane) completed the 1-year study period. Fat mass had significantly decreased by month 12 in the exemestane, but not in the tamoxifen group; the between-group difference was statistically significant (P<0.01). The FFM/FM ratio had significantly increased in the exemestane group, but not the tamoxifen group; the between-group difference was statistically significant (P<0.05). Triglycerides and high-density lipoprotein cholesterol significantly decreased (P<0.01; P<0.05), and low-density lipoprotein cholesterol significantly increased (P<0.01) in the exemestane group at the end of the 1-year study period. Our findings suggest that switching patients to adjuvant exemestane treatment after at least 2 years of tamoxifen therapy may be associated with an advantage over continuing adjuvant tamoxifen treatment in terms of body composition.     

Effect of anastrozole and tamoxifen on lipid metabolism in Japanese postmenopausal women with early breast cancer

Endocrine therapies that profoundly decrease estrogen levels potentially have a detrimental effect on the cardiovascular system. This study evaluated the effect on lipid metabolism of one such agent, the new generation aromatase inhibitor anastrozole, compared with tamoxifen, when used as adjuvant treatment in postmenopausal Japanese women with early breast cancer. All patients had completed primary surgery and were randomized to anastrozole 1 mg once daily (n=22) or tamoxifen 20 mg once daily (n=22). Anastrozole significantly reduced levels of triglycerides and remnant-like particle cholesterol, whereas tamoxifen significantly increased these. Activity of lipoprotein lipase and levels of high-density lipoprotein cholesterol significantly increased after anastrozole treatment. In contrast, activity of hepatic triglyceride lipase, also a key enzyme of triglyceride metabolism, significantly decreased following treatment with tamoxifen. We thus conclude that in our study anastrozole had a beneficial effect on lipid profiles of postmenopausal women with early breast cancer after 12 weeks of treatment.     

Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer

At the present time, tamoxifen is the most widely used anti-estrogen for adjuvant therapy and metastatic disease in postmenopausal women with breast cancer, a population at high risk for osteoporosis. This prospective study was designed to evaluate the effect of adjuvant tamoxifen on bone mineral density and all biochemical markers concomitantly in women with early-stage breast cancer in one study. Using dual-energy X-ray absorptiometry, prior to and 12 mo after tamoxifen treatment, bone mineral density in lumbar spine and femoral neck was measured in 44 women with T1-T2N0M0 estrogen-receptor-positive breast cancer receiving adjuvant treatment with tamoxifen 20 mg/d. Biomarkers that can affect bone mineral metabolism were measured before and after 3 and 12 mo of tamoxifen treatment. Bone mineral density was minimally increased in lumbar spine and femoralneck after 12 mo treatment with tamoxifen (p=0.79 and 0.55, respectively). No differences were found in serum levels of calcium, phosphate, creatinine, ALAT, albumin, LDH, calcitonin, or estradiol. A significant decrease in osteocalcin levels was found after 3 and 12 mo (p≤0.01). TSH and PTH levels were increased (p≤0.05) after 3 mo, returning to baseline after 12 mo. In conclusion, tamoxifen has an estrogen-like effect on bone metabolism in postmenopausal women and is associated with preservation of bone mineral density in lumbar spine and femoral neck. Changes in serum concentration of biochemical markers may reflect decreased bone turnover or bone remodeling and add to the understanding of tamoxifen’s effect on bone mineral density.     

Changes in serum lipid and lipoprotein levels in postmenopausal patients with node-positive breast cancer treated with tamoxifen

Tamoxifen has been used for a long time as an adjuvant hormonal treatment in breast cancer patients. We studied 62 newly diagnosed postmenopausal women, aged 50-79 years, with node-positive breast cancer and receiving adjuvant tamoxifen (20 mg per day). Total serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, apo AI, apo AII, apo B and Lp(a) were determined before the surgery and 3, 6, 9, 12 and 24 months after starting tamoxifen treatment. Tamoxifen significantly reduced total serum cholesterol (6.13+/-1.20 mmol/L vs 5.21+/-1.05 mmol/L) (P <0.01), LDL-cholesterol (3.72+/-0.70 mmol/L vs 2.93+/-0.51) (P <0.01) and Lp(a) (0.11+/-0.07 g/L vs 0.02+/-0.01 g/L) (P < 0.01). There were no changes in triglycerides or HDL-cholesterol serum levels during tamoxifen treatment. The results indicate that an additional beneficial effect of adjuvant tamoxifen therapy may be that it decreases cardiovascular risk in such patients.     

Bone Mineral Density and Lipid Changes During 5 Years of Follow-up in a Study of Prevention of Breast Cancer with Toremifene in Healthy,High-risk Pre- and Post-menopausal Women

Summary A double-blind, randomised, placebo-controlled pilot study was initiated to evaluate the feasibility of chemoprevention with toremifene 60 mg/day in healthy women at high risk for breast cancer. Enrolment in the study was terminated earlier than planned because of slow patient accrual, although 13% of patients continued for 5 years. The revised efficacy outcomes were change in bone mineral density (BMD) from baseline at four skeletal sites, plus effects on serum lipids. In premenopausal women there was a trend for sustained increase in BMD during toremifene therapy after year 1 in lumbar spine. In postmenopausal women, toremifene had little or no effect on BMD trends. Levels of total and low-density lipoprotein (LDL) cholesterol were largely unchanged from baseline in premenopausal women treated with toremifene but were often slightly lower than in the placebo group during follow-up. Total and LDL cholesterol levels declined slightly from baseline in the postmenopausal women and were, at several points during the first 3 years, significantly lower than in the corresponding placebo group (p < 0.01). We conclude that: (a) assessment of toremifene 60 mg/day in chemoprevention will require further clinical trials; (b) toremifene 60 mg/day has no substantive negative effects on BMD in pre- or postmenopausal women and may exert a minor favourable influence (in particular, the effects of toremifene 60 mg/day on BMD in premenopausal women may make the drug an attractive alternative to tamoxifen 20 mg/day for that patient subset); (c) lipid effects of toremifene 60 mg/day are, at minimum, neutral and may be modestly favourable for reducing cardiovascular risk.     

The Effect of Exemestane on the Lipidemic Profile of Postmenopausal Early Breast Cancer Patients: Preliminary Results of the TEAM Greek Sub-study

Summary Introduction. Long-term endocrine therapy for breast cancer may have clinical implications as drugs that potentially alter the lipid profile may increase the risk of developing cardiovascular disease. In this study, a companion sub-protocol to the TEAM (Tamoxifen and Exemestane Adjuvant Multicenter) International trial, we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of postmenopausal women with early breast cancer in the adjuvant setting to that of tamoxifen. Patients and methods. In this open-label, randomized, parallel group study, 176 postmenopausal patients with estrogen and/or progesterone receptor positive early breast cancer were randomized to either adjuvant exemestane (25 mg/day; n = 90) or tamoxifen (20 mg/day; n = 86). Assessments of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and serum triglycerides (TRG) were performed at baseline and every 3 months for the first 12 months. Results. Serum triglyceride levels were consistently increased above baseline throughout the study in the tamoxifen arm, while there was a trend towards reduction in the exemestane arm. There was also an overall trend for tamoxifen to decrease the levels of LDL throughout the study period. Exemestane did not demonstrate any other significant change in HDL levels; however, there was a consistent trend for a reduction in total cholesterol in both treatment arms. The atherogenic risk determined by the TC:HDL ratio remained stable in both arms throughout the treatment period. Conclusions. Exemestane appears to have a neutral effect on total cholesterol and HDL levels. Unlike tamoxifen’s positive effect on LDL levels, exemestane does not significantly alter LDL levels. Tamoxifen on the other hand increases triglyceride levels, while exemestane results in a beneficial reduction in TRG levels. These data offer additional information with regard to the safety and tolerability of exemestane in postmenopausal breast cancer patients and support further investigation of its potential usefulness in the adjuvant setting.     

Effects of prednisolone on sex hormone binding globulin during primary endocrine treatment of advanced breast cancer

Summary Serum sex hormone binding globulin (SHBG) was measured in 21 pre and 39 postmenopausal women with advanced breast cancer before treatment and 1, 3, 6, 9 and 12 months after ovarian irradiation or during continuous administration of tamoxifen at a dose of 10 mg twice daily, respectively; some patients received additional prednisolone at a dose of 5 mg twice a day.Ovarian irradiation was associated with a 25% reduction in serum SHBG levels 3 to 6 months after treatment whilst patients on tamoxifen experienced a rise of about 80% in serum SHBG levels after 1 to 3 months. In postmenopausal women prednisolone markedly dampened the effect of tamoxifen, reducing a 80% rise to about 20%. There was no relationship between SHBG levels and response to treatment.     

The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L).

BACKGROUND: The purpose of this study was to evaluate changes in serum lipid parameters {cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and lipoprotein(a) [Lp(a)]}, in postmenopausal women receiving letrozole or placebo after adjuvant tamoxifen for early stage breast cancer (NCIC CTG MA.17L). PATIENTS AND METHODS: MA.17L is a substudy of MA.17, a randomized, double-blind, placebo-controlled trial of letrozole 2.5 mg taken daily for 5 years in postmenopausal women with primary breast cancer completing approximately 5 years of prior adjuvant tamoxifen. Patients consenting to participate in this companion study had blood drawn and lipid parameters (total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a), triglycerides) evaluated at baseline, 6 months, 12 months and yearly thereafter until completion of protocol therapy. It was required that women be non-hyperlipidemic and not taking lipid-lowering drugs at time of entry on this trial. RESULTS: Three hundred and forty seven women were enrolled in the study. The letrozole and the placebo groups demonstrated marginally significant differences in the percentage change from baseline in HDL cholesterol at 6 months (P=0.049), in LDL cholesterol at 12 months (P=0.033) and triglycerides at 24 months (P=0.036). All comparisons of lipid parameters at other time points were not significantly different between the two treatment groups. No statistically significant differences in the number of patients exceeding the thresholds defined for the lipid parameters were found between the two treatment groups. CONCLUSIONS: The MA.17 trial demonstrated a significant improvement in disease-free survival with the use of letrozole as extended adjuvant therapy post tamoxifen. Results from this study suggests that letrozole does not significantly alter serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or Lp(a) in non-hyperlidiemic postmenopausal women with primary breast cancer treated up to 36 months following at least 5 years of adjuvant tamoxifen therapy. These findings further support the tolerability of extended adjuvant letrozole in postmenopausal women following standard tamoxifen therapy.     

The Christie Hospital adjuvant tamoxifen trial.

A clinical trial was carried out at The Christie Hospital, Manchester, England, between November 1976 and June 1982. Following surgery, patients with clinical stage T1-T3a, N1-N2b, M0 tumors were randomly allocated in the following way: premenopausal women to either tamoxifen 20 mg/day for 1 year or to an irradiation-induced menopause; postmenopausal women to either tamoxifen for 1 year or no further treatment (controls). In the node-negative subgroup, an analysis at a median follow-up of 10 years shows no statistically significant difference in overall or disease-free survival between tamoxifen-treated patients and irradiation-induced menopause and control patients. Side effects were few, and compliance was excellent. There was no significant increase of second primary tumors in target endocrine organs in the tamoxifen-treated patients. For the whole series of 961 patients, a log-rank analysis of events, allowing for node status, still shows a statistically significant benefit for tamoxifen-treated patients (P = .04).     

Are the effects of tamoxifen on the serum lipid profile modified by apolipoprotein E phenotypes?

BACKGROUND: Tamoxifen has favorable effects on the serum lipid profile. It has been suggested that the apolipoprotein (Apo) E phenotype can influence serum lipid parameters; the ApoE allele 4 (ApoE4) is associated with higher total and low-density lipoprotein (LDL) cholesterol levels. The ApoE phenotype also affects lipid responses to diets or treatment with statins. However, the effect of tamoxifen on the lipid profile in different ApoE phenotypes is unknown. PATIENTS AND METHODS: In the present study, we evaluated the effects of tamoxifen on the serum lipid profile in 11 ApoE4-positive postmenopausal women with breast cancer (phenotypes 3/4 and 4/4) compared with 33 ApoE4-negative women (phenotypes 3/2 and 3/3). Serum lipid parameters [high-density (HDL), LDL and total cholesterol, triglycerides, ApoAI, ApoB and lipoprotein (a)] were measured after an overnight fast before treatment and after 3 and 12 months. ApoE isoforms were determined by isoelectric focusing of delipidated very-low-density lipoproteins (VLDL). RESULTS: During the follow-up period, serum levels of total and LDL cholesterol and ApoB decreased significantly in both groups, but no significant differences were found. Concentrations of serum HDL cholesterol were not significantly different between both groups. However, serum ApoAI levels increased significantly in ApoE4-negative subjects (p = 0.00005), but no significant changes in ApoE4-positive women were observed. Serum triglyceride levels increased by 23.2% (p < 0.05) in ApoE4-positive patients, but they did not change significantly in ApoE4-negative patients. The LDL/HDL cholesterol ratio decreased similarly in the two groups, but the ApoAI/ApoB ratio, which may be a better predictor of cardiovascular events, significantly changed in the ApoE4-negative subjects. Finally, the median level of Lp(a) decreased by 43.4% in the ApoE4-negative patients, whereas it did not change significantly in the ApoE4-positive group. CONCLUSION: In postmenopausal Greek women with breast cancer, the levels of Lp(a) and triglycerides and the ApoAI/ApoB ratio respond more favorably to tamoxifen treatment in ApoE4-negative than in ApoE4-positive patients.     

Lipid concentrations in postmenopausal women on letrozole after 5?years of tamoxifen: an NCIC CTG MA.17 sub-study

To evaluate changes in serum lipid parameters (cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and lipoprotein(a) [Lp(a)]), in postmenopausal women receiving letrozole after tamoxifen therapy. MA.17L is a sub-study of MA.17, a double-blind, placebo-controlled trial of extended adjuvant letrozole. Eligible postmenopausal women were non-hyperlipidemic and not on lipid-lowering drugs. This analysis considers the 183 patients on the letrozole arm. Lipid parameters evaluated at baseline, 6?months, 12?months, and yearly thereafter until completion of 5?years of letrozole. The median duration of letrozole treatment was 5.0?years with a range from 0.03 to 6.05?years. After 5?year tamoxifen, patients on letrozole experienced significant increases from baseline in total cholesterol, LDL cholesterol, and Lp(a) at all study time points but no statistically significant changes in triglycerides. Specifically, a statistically significant increase was found at 60?months in total cholesterol [mean percentage change from baseline (PC) 5.27; p?=?0.003], HDL cholesterol (mean PC 6.75; p?=?0.003), LDL cholesterol (mean PC 10.02; p?=?0.001), Lp(a) (mean PC 105.95; p?<?0.0001). 103 (56?%) women in the study had clinically significantly elevated levels of Lp(a) (106?% above baseline) after 5?years of therapy. The results were similar after excluding the 21?% of patients who had ever received anti-lipid treatment. Significant increases in total cholesterol, HDL cholesterol, LDL cholesterol, and, most notably, Lp(a) in postmenopausal women were observed following 5?years of adjuvant letrozole treatment and after 5?years of tamoxifen therapy and such patients should have monitoring of their lipid levels in clinical practice.     

Serum cholesterol reduction with tamoxifen

Summary The serum cholesterol levels of 123 consecutively and newly diagnosed women with Stage I and II breast cancer taking tamoxifen were compared with a control group of 81 consecutively newly diagnosed women with Stage I and II breast cancer who were not taking a hormonal treatment or supplement. Other factors that were evaluated were age, menopausal status, tumor size, weight, height, Quetelet index, and smoking and alcohol intake history.The mean cholesterol change in patients on tamoxifen (34.2 ± 3.6 mg/dl) was significantly greater than controls (1.0 ± 4.1 mg/dl) (P<0.001). Serum cholesterol fell by more than 10 mg/dl in 72.9% of women on tamoxifen vs. 35.1% of controls and by more than 40 mg/dl in 39.9% of women on tamoxifen vs. 12.6% of controls. Multivariate analysis revealed that tamoxifen administration (P<0.0001), initial cholesterol level (P = 0.001), and age (P = 0.04) were significant factors in producing a decrease in serum cholesterol.The administration of tamoxifen as adjuvant therapy to women with newly diagnosed breast cancer resulted in a significant fall in serum cholesterol. This effect of tamoxifen on the serum cholesterol may prove to be an additional benefit in the form of reduced cardiovascular risk in these women.     

Health-related quality of life,psychological distress,and adverse events in postmenopausal women with breast cancer who receive tamoxifen,exemestane, or anastrozole as adjuvant endocrine therapy: National Surgical Adjuvant Study of Breast Cancer 04 (N-SAS BC 04)

Health-related quality of life (HRQOL), symptoms of depression, and adverse events (AEs) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer (BC) who received adjuvant tamoxifen, exemestane, or anastrozole in an open-labeled, randomized, multicenter trial designated as the National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04 substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. During the first year of treatment, HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and its Endocrine Symptom Subscale (ES), and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. In addition, predefined AEs were analyzed. A total of 166 eligible patients were randomly assigned to receive adjuvant tamoxifen, exemestane, or anastrozole. FACT-B scores increased after treatment began and remained significantly higher in the tamoxifen group than in the exemestane group or anastrozole group during the first year (P = 0.045). FACT-B scores were similar in the exemestane group and anastrozole group. ES scores and CES-D scores were similar in all treatment groups. Arthralgia and fatigue were less frequent, but vaginal discharge was more frequent in the tamoxifen group than in the exemestane group or anastrozole group. HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole. HRQOL and AEs were similar with exemestane and anastrozole. Given the results of the TEAM trial, upfront use of tamoxifen followed by an aromatase inhibitor (AI) may be an important option for adjuvant endocrine therapy in Japanese postmenopausal women.     

Serum lipid levels during and after adjuvant toremifene or tamoxifen therapy for breast cancer

Tamoxifen decreases serum cholesterol (S-cholesterol) level about 10% and low-density lipoprotein cholesterol (S-LDL) 15–20%, but in most studies it has increased serum triglyceride levels and had little effect on serum high-density cholesterol (S-HDL). The effect of another antiestrogen, toremifene, on the serum lipid profile has not been completely studied. We monitored serum lipid levels longitudinally in 141 axillary node-positive postmenopausal breast cancer patients who received randomly either 40mg toremifene or 20mg tamoxifen as adjuvant therapy for 36 months, and in 34 postmenopausal women who received no adjuvant systemic therapy after surgery for axillary node-negative breast cancer. No significant differences were found between the drugs in their effects on S-cholesterol, LDL, HDL, or triglyceride levels, or on the cholesterol-to-HDL or LDL-to-HDL ratios. For both drugs the S-cholesterol and S-LDL absolute lowering effect was the greater the higher the pretreatment level. For a patient with a median pretreatment value, toremifene decreased S-cholesterol 6% and tamoxifen 13%, and S-LDL decreased by 13% and 23%, respectively, at 6 months of therapy. Six months after stopping three-year antiestrogen therapy S- cholesterol and S-LDL levels had returned to the pretreatment levels. In conclusion, we found no major differences between 40mg toremifene and 20mg of tamoxifen in their effect on the serum lipid levels, which return to the pretreatment levels within 6 months after cessation of therapy.     

Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.     

The latest is the greatest? Results of a structured lecture about aromatase inhibitor use for breast cancer

Summary Background The aromatase inhibitors (AIs) are increasingly surpassing tamoxifen as the endocrine treatment of choice for postmenopausal breast cancer patients. With their increasing use, there is concern that they are being inadvertently prescribed to pre- and peri-menopausal women. Methods As part of a continuing medical education program for 264 practicing surgeons, a 15-min lecture was given over viewing hormone therapy for early stage breast cancer. Two multi-choice questions were asked before and after the lecture regarding the optimal hormonal treatment for pre and postmenopausal women. Results For the optimal treatment of premenopausal women, 36% of respondents chose tamoxifen before the lecture, rising to 82% after it (p<0.01). However 37% suggested an AI would be best, with a further 27% choosing either an AI or tamoxifen, falling to 7% and 11% respectively after the lecture. Before the lecture, 30% of the participants stated that any of the listed treatment options; tamoxifen alone, an AI alone or a combination of tamoxifen and an AI would be acceptable for postmenopausal women. Following the lecture, 53% chose this option (p<0.01). Conclusions In many countries it is practicing surgeons who commence endocrine therapy for patients with breast cancer. The findings of this study are useful from two points. Firstly it is clear that many physicians feel that AIs are an effective adjuvant endocrine therapy for premenopausal breast cancer. Secondly it demonstrates the benefits of continuing medical education as a significant improvement in test scores was noted after a structured lecture.     

Tamoxifen and aromatase inhibitors differentially affect vascular endothelial growth factor and endostatin levels in women with breast cancer.

PURPOSE: Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance. We explored the effects of tamoxifen and aromatase inhibitors on concentrations of VEGF and endostatin in plasma, serum, and platelet releasate (induced by platelet activation). EXPERIMENTAL DESIGN: VEGF and endostatin concentrations were measured with a quantitative immunoassay before and after 1 to 5 weeks of treatment in 30 women with breast cancer treated with either tamoxifen (n = 14) or aromatase inhibitors (n = 16). Platelet activation was induced by a thrombin receptor agonist. RESULTS: Tamoxifen therapy resulted in an increase in platelet releasate concentrations of VEGF (P = 0.01) but no change in plasma VEGF. In contrast, aromatase inhibitor therapy did not affect serum, plasma, or platelet releasate VEGF. In univariate analysis, aspirin use attenuated the tamoxifen-associated increase in VEGF in the platelet releasate and decreased serum levels of VEGF (P = 0.03). Aromatase inhibitor therapy resulted in a decrease in serum endostatin concentrations (P = 0.04), whereas plasma concentrations of endostatin tended to be higher during treatment with aromatase inhibitors (P = 0.06). Tamoxifen therapy resulted in no change in serum or plasma endostatin concentrations. Platelet releasate concentrations of endostatin did not change with either treatment. Interindividual variability was noted among both aromatase inhibitor--and tamoxifen-treated patients. CONCLUSIONS: Tamoxifen and aromatase inhibitor therapy affect VEGF and endostatin levels and likely contribute to the angiogenic balance in breast cancer patients. Aspirin decreased the proangiogenic effects of tamoxifen, suggesting that antiplatelet and/or antiangiogenic therapy might improve the effectiveness of tamoxifen in women with breast cancer.