Duration of tamoxifen effect on lipidemic profile of postmenopausal breast cancer patients following deprivation of treatment.

OBJECTIVE: It was the aim of this study to investigate the effect of tamoxifen withdrawal on markers of lipid metabolism in postmenopausal women with breast cancer who completed tamoxifen therapy and received no further treatment. METHODS: Lipidemic profile changes were studied in 190 postmenopausal patients with operable breast cancer, following cessation of 5-7 years of tamoxifen treatment. Assessments of total cholesterol, high-density lipoprotein, low-density lipoprotein and total serum triglycerides were performed at baseline, 6 months and 12 months. RESULTS: By 6 months, both total cholesterol and low-density lipoprotein levels were significantly increased, and total triglyceride levels were significantly reduced compared with baseline values and maintained to 12 months. There was no significant alteration observed for high-density lipoprotein levels over the study period. CONCLUSION: The beneficial effect of tamoxifen on the lipidemic profile of postmenopausal breast cancer patients seems to be lost in less than 12 months time following cessation of 5-7 years of tamoxifen treatment. A 'rebound effect' on the lipidemic parameters should be expected and those patients should be monitored carefully.

The effect of exemestane on the lipidemic profile of postmenopausal early breast cancer patients: preliminary results of the TEAM Greek sub-study.

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.

Effect of exemestane on the lipidemic profile of post-menopausal operable breast cancer patients following 5-7 years of adjuvant tamoxifen: preliminary results of the ATENA substudy.

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 subprotocol to the ATENA (Adjuvant post-Tamoxifen Exemestane versus Nothing Applied) trial, we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of post-menopausal women with operable breast cancer in the adjuvant setting to that of observation alone following deprivation of 5-7 years primary treatment with tamoxifen. In this open-label, randomized, parallel group study, 340 post-menopausal patients with operable breast cancer who had been treated with tamoxifen for 5-7 years were randomized to either 5 additional years of exemestane (25 mg/day; n=172) or observation alone (n=168). Assessments of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total serum triglycerides (TRG) were performed at baseline, and at 6 and 12 months. Total TRG levels were significantly reduced compared with baseline for the exemestane and the observational arm. Both total cholesterol and LDL levels were significantly increased above that of baseline values by 6 months, maintained through to 12 months, with no significant difference between the two treatment arms. There was no significant alteration observed for HDL over time or between the two arms. We conclude that sequential adjuvant treatment with exemestane in post-menopausal operable breast cancer patients following cessation of 5-7 years of tamoxifen does not appear to significantly alter the lipidemic profile for at least 12 months compared with an observational arm.

Pregnancy and offspring after the appearance of breast cancer.

The objective of this study was to investigate the influence of pregnancy in breast cancer prognosis of women under the age of 35 years. Two hundred and forty-three women with breast cancer, from three oncology departments in Athens, were investigated. Twenty-one got pregnant (7.91%) 7-100 months after breast cancer diagnosis and in a median time period of 31 months. All women had mastectomy apart from 2 who had only lumpectomy as surgical procedure. Thirteen of 21 were treated with radiotherapy and 17 of 21 had also adjuvant chemotherapy mainly with CMF for 6 cycles. Sixteen children from 14 mothers were born and the rest of the patients underwent an abortion between the 2nd and 5th month of pregnancy. All children were healthy and grew up normally up to the age of 12-142 months (end of the study) and their median age of 51 months. Only 2 patients had stage III disease at diagnosis while the remaining 19 had stage I-IIb. Three cancer recurrences were observed (14.3%) after 7-84 months. One patient had a second primary-ovarian cancer 60 months after mastectomy. Recurrence rate and survival compared with those of nonpregnant women of the same age and the stages of disease were not different. To conclude: the present study indicates that healthy offsprings can be delivered from breast cancer patients, and pregnancy does not seem to play any role in tumor recurrence.

Locally advanced breast cancer: the contribution of cytotoxic and endocrine treatment to radiotherapy. An EORTC Breast Cancer Co-operative Group Trial (10792).

Patients with locally advanced carcinoma of the breast were randomized to receive either radiotherapy alone, radiotherapy + endocrine therapy, radiotherapy + chemotherapy or radiotherapy + endocrine therapy + chemotherapy. In 363 evaluable patients, time to first progression was delayed significantly by both endocrine treatment and chemotherapy, the greatest effect being achieved by the combination of endocrine treatment and chemotherapy. This effect was almost entirely due to a major effect of systemic treatment on time to loco-regional progression, for which the result is highly significant, rather than time to distant metastasis in which only a non-significant trend was observed. For survival, a trend was seen in favour of the combination of hormone treatment and chemotherapy, but this effect did not achieve statistical significance. This trial suggests that current endocrine and cytotoxic treatments are only of marginal value in improving the prognosis in locally advanced breast cancer.

Risk of breast cancer among Greek women in relation to nutrient intake.

A case-control study of the role of diet in the cause of breast cancer was conducted in Athens, Greece. The case series consisted of 120 consecutive patients with histologically confirmed breast cancer admitted to either of two teaching hospitals over a 12-month period. The controls were 120 patients admitted to a teaching hospital for trauma and orthopedic conditions during the same period. Dietary histories concerning the frequency of consumption of 120 foods and drinks were obtained by interview. Nutrient intakes for individuals were estimated by multiplying the nutrient content of a selected typical portion size for each specified food item by the frequency that the food was used per month and summing these estimates for all food items. Cases reported significantly less frequent consumption of vitamin A after controlling for total caloric intake, potential external confounding variables and other nutrients associated with breast cancer risk. The odds ratio estimated for consumption of vitamin A equal to the value of the 90th centile versus consumption equal to the value of the 10th centile was 0.46 with 90% confidence limits 0.26-0.82. There was no evidence that high intake of dietary fat increases the risk of breast cancer.

Thyroid disease in patients with benign and malignant mastopathy.

The incidence of thyroid disease was examined prospectively in 97 consecutive patients with breast cancer (Group I) and was compared with that of 61 women with cystic breast disease (Group II) and that of 60 control women (Group III) with no breast problems. Thyroid enlargement was found in 47%, 49%, and 22% of those in Groups I, II, and III, respectively, and treatment with thyroid hormones was taken by 9.3% (I), 8.2% (II), and 5.0% (III) of the cases. The mean thyroid-stimulating hormone (TSH) concentration in those in Group I (5.4 +/- 2.2 microU/ml) was significantly higher than in Groups II (3.9 +/- 1.9, P less than 0.01) and III (4.0 +/- 1.8, P less than 0.001), whereas thyroid microsomal antibodies were detected in 13.4% (I), 9.1% (II), and 1.7% (III); mean triiodothyronine (T3) and thyroxin (T4) concentrations were similar in the three groups. When both TSH and T3 concentrations were taken into account, 24% and 17% of the patients, respectively, from Group I were no longer in the Group III range; the corresponding figures for Group II were 13% and 23%, respectively. These results indicate that breast cancer and thyroid disease are probably related, but not in a specific way, since benign mastopathy also seems to be associated with thyroid disturbances.

Seasonal variations in the frequency distribution of breast cancer in Greek women according to the month of their birth.

The frequency distribution of patients with breast cancer according to the month of their birth was examined in 1,165 women comprising the total number of patients recorded in our cancer registry from 1975 until the end of 1982. Statistical evaluation of this material using an exact chi 2 for simple null hypothesis demonstrated the existence of two high frequency peaks corresponding to March and April in the spring and September in the autumn. These frequencies were significantly higher (P less than 0.001) than those of the remaining months. Confirmation of this finding would imply the introduction of a new variant in breast cancer epidemiology.

The incidence of positive oestrogen and progesterone receptors in breast cancer of Greek women.

Oestrogen and progesterone receptors were determined in breast tumours of 80 Greek women. Oestrogen-positive receptors were found in 84.6% of the pre (n = 39) and 85.4% of the postmenopausal (n = 41) patients while progesterone-positive receptors were found in 71.8% of these women respectively. In combination, 69.2% of the pre-menopausal had both receptors detectable, 15.4% had oestrogen-positive and progesterone-negative and 2.6% had oestrogen negative and progesterone-positive while 12.8 had no detectable receptors. This incidence in postmenopausal women was 51.2, 34.2, 0.0, 14.6% respectively. The ratio of progesterone to oestradiol receptor concentration was 7.6 in the pre- and 1.7 in the postmenopausal group (p less than 0.05). In conclusion, the incidence of positive receptors in Greek women with breast cancer is similar to that of other Western populations.