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ABSTRACT: To investigate the efficacy of letrozole 2.5 mg and 10 mg used as primary neoadjuvant therapy for patients with locally advanced and large operable breast cancer.
Twenty-four postmenopausal patients with locally advanced or large operable breast cancer were treated in two consecutive series with letrozole 2.5 mg (n = 12) or letrozole 10 mg (n = 12). Response at three months was measured by change in tumor volume according to WHO criteria (partial response was defined as a reduction in tumor volume > or = 65%). Tumor volumes were assessed clinically, by ultrasound and mammography, and pathologically.
All 24 patients were estrogen receptor-positive, were considered 'receptor-rich', and mean age was 77.6 years and 71.6 years in the letrozole 2.5 mg and 10 mg treatment groups, respectively. There were five complete clinical responses and seven partial clinical responses in the patients treated with 2.5 mg letrozole, and nine partial responses and three patients with stable disease in patients treated with 10 mg letrozole. Assessed by ultrasound and mammography, the 12 patients treated with 2.5 mg had one complete response, nine partial responses and two with no change. In the 12 patients treated with 10 mg letrozole, imaging gave eight partial responses and four with no change. One patient treated with the 2.5 mg dose had a complete clinical and pathological response. There was no significant difference between the two doses in effect on tumor volume, and no recordable side effects associated with either dose.
Letrozole used in a neoadjuvant setting is highly effective, producing clinically beneficial reductions in tumor volume allowing all patients to have breast conserving surgery, and has an acceptable safety profile.
Breast Cancer Research and Treatment 04/2001; 66(3):191-9. · 4.43 Impact Factor
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ABSTRACT: Endometrial thickening as seen on ultrasound scan of women on tamoxifen is well documented. To examine whether this phenomenon is reversible 20 women with thickened endometrium on scan but atrophic endometrium on further assessment underwent repeat ultrasound scan 6-11 months following tamoxifen cessation. Endometrial thickness reduced significantly in the majority of women off tamoxifen from a mean of 12.4 mm on tamoxifen to a mean of 7.8 mm off tamoxifen (P=0.0013).
The Breast 07/2000; 9(3):156-7. · 2.49 Impact Factor
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ABSTRACT: Postmenopausal patients with oestrogen receptor-positive locally advanced T4b, N0-1, M0 and large operable breast cancers T2>3 cm, T3, T4, N0-1 and M0 have been treated with 2.5 mg letrozole (12 patients), 10 mg letrozole (12 patients), 1 or 10 mg anastrozole (24 patients) and 20 mg tamoxifen (65 patients). There was no apparent difference in response rate between 2.5 and 10 mg letrozole. Only 17 patients with anastrozole have so far completed the 3-month treatment period. Median clinical, mammographic and ultrasound reductions in tumour volumes for patients treated with letrozole were 81% (95% confidence interval (CI) 66-88), 77% (95% CI 64-82) and 81% (95% CI 69-86) respectively and for anastrozole, values were 87% (95% CI 59-97), 73% (95% CI 58-82) and 64% (95% CI 52-76) respectively. This compares with a median reduction in tumour volume for tamoxifen-treated patients as assessed by ultrasound of 48% (95% CI 27-48). There were seven complete clinical responses (CR), sixteen patients who achieved 50% or greater reduction in tumour volume (PR) and one no change (NC) for letrozole and four CRs, twelve PRs and one progressive disease for anastrozole. Best radiological responses were one CR, twenty PRs and three NCs for letrozole and one CR, fifteen PRs and one NC for anastrozole. This study has shown that the new aromatase inhibitors, letrozole and anastrozole, are highly effective agents in the neoadjuvant setting and they should now be compared with tamoxifen as first-line treatment in a randomised study.
Endocrine Related Cancer 07/1999; 6(2):227-30. · 4.36 Impact Factor
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ABSTRACT: Tamoxifen is the most commonly prescribed adjuvant therapy for women with breast cancer. It has agonist activity on the endometrium and is associated with an increased risk of endometrial cancer. The aim of this study was to evaluate whether screening with transvaginal ultrasound (TV USS) with or without hysteroscopy is worthwhile.
A total of 487 women with breast cancer, 357 treated with tamoxifen and 130 controls, were screened with TV USS, and endometrial thickness was measured. Women with thickened endometrium underwent outpatient hysteroscopy.
Length of time on tamoxifen ranged from 5 to 191 months (mean, 66 months), and endometrial thickness ranged from 1 to 38 mm (mean, 7.3 mm). Women treated with tamoxifen had significantly thicker endometrium than did controls (P <.0001). There was a statistically significant (P <.0001) positive correlation between length of time on tamoxifen and endometrial thickness. One hundred forty-five women had endometrium greater than 5 mm on USS, and 134 underwent successful outpatient hysteroscopy, 61 of whom had atrophic endometrium, resulting in a 46% false-positive scan rate. The remaining women all had benign features to explain the USS findings.
TV USS detects a high incidence (41%) of apparent endometrial thickening in women treated with tamoxifen, although 46% had atrophic endometrium on further assessment, and none of the remaining asymptomatic women had significant lesions. Length of time on tamoxifen relates to endometrial thickening as measured by TV USS. TV USS is a poor screening tool because of the high false-positive rate. The low frequency of significant findings suggests that endometrial screening in asymptomatic women is not worthwhile.
Journal of Clinical Oncology 07/1999; 17(7):2050-4. · 18.37 Impact Factor
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ABSTRACT: To review the outcome of pregnancies complicated by placenta praevia over a three-year period (1991-1993) and to describe in detail the antenatal course and the events leading to delivery, assessing retrospectively whether there are clinical features predictive of outcome and whether outpatient management would be reasonable.
A retrospective review of the case records of women with a pregnancy complicated by placenta praevia.
A tertiary referral teaching hospital in Edinburgh.
There were 15,930 deliveries in the study period. Fifty-eight women (0.4%) had a placenta praevia in the third trimester, 42 of whom (72%) had at least one episode of bleeding. Overall, 62% of the women had a major praevia with no differences in the grade of praevia between those women who did or did not have bleeding. Both diagnosis and delivery occurred significantly earlier in women with antepartum bleeding than in those without (median gestation at diagnosis 28.6 weeks versus 33.3 weeks (P < 0.01) and at delivery 36.0 weeks versus 37.1 weeks (P = 0.04), respectively). Delivery by emergency caesarean section was more common in women with bleeding (62% versus 38%). An increasing number of bleeding episodes experienced by individuals was not associated with significant differences in outcomes. Rapid emergency delivery for bleeding was necessary for three women, in none of whom could the bleeding have been predicted.
The clinical outcomes of placenta praevia are highly variable and cannot be predicted confidently from antenatal events. Nonetheless, in the majority of cases with or without bleeding and irrespective of the degree of praevia, outpatient management would appear safe and appropriate.
British Journal of Obstetrics and Gynaecology 09/1996; 103(9):864-7.
