P. Dillon’s research while affiliated with Western General Hospital and other places

Over a 5-year period, 75 patients with locally advanced breast cancer presenting to the Edinburgh Breast Unit were managed with a policy of infusional primary chemotherapy. For 65 patients, the regimens comprised infusional 5 fluorouracil with anthracycline and/or either cyclophosphamide or cisplatinum (AcF, CAF or ECF) whilst 10 older patients had CMF-inf. The overall activity and tolerability for the regimens was good with a 76% objective response rate including 15% clinical complete responses. Surgery was possible in 64% and pathological complete responses confirmed in 7 (9.3%). Median disease free survival (DFS) is 5.23 years. Factors predicting for DFS or Overall Survival (OS) were assessed in this small group and ER positive patients did better than ER negative although there was surprisingly no negative DFS or OS association with inflammatory disease or advancing age. We found a paradoxical interaction with use of post-chemotherapy tamoxifen which was significantly associated with poorer DFS and OS overall and in the ER negative subgroups.

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.

A retrospective review of case records was performed of 110 patients who underwent 124 total duct excisions during the period 1989–1995. All patients were sent a questionnaire and 88 fully completed questionnaires from 100 total duct excisions were analysed. All operations were performed according to a standard technique utilizing a circumareolar incision and all operations were performed under antibiotic cover. Immediate postoperative wound morbidity was low with only 4 wound infections. Of the 100 operations assessed from the questionnaires, 94 patients rated the cosmetic result as excellent or good. Nipple sensation improved after 24 operations but decreased or was absent after 26 operations. Patients who reported pain prior to operation, those who smoked and those who had a past history of multiple episodes of periareolar sepsis were significantly more likely to have decreased nipple sensation following surgery (P = 0.045, P = 0.015 and P = 0.007, respectively). Patients who reported that the position of the nipple was improved by surgery were significantly more likely to report improvement in nipple sensation (P = 0.01). Total duct excision is an operation that can be performed with acceptable postoperative wound complications but is associated with significant changes in nipple sensation, and patients should be warned of this.