Biomedical subjects
Publications and source records attributed to A P Forrest.
The relation between oestrogen receptor status of primary breast cancer as determined immuncytochemically on fine-needle aspirates and the response to tamoxifen therapy has been assessed in 52 patients. The proportion of cells staining correlated well with the likelihood of response, which emphasises the importance of tumour heterogeneity.
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This report details the outcome after clinical diagnosis of mammary fibroadenoma in 110 women aged under 35 years. After fine needle aspiration cytology, and subsequent exclusions and failures of follow-up, 92 lesions were observed for a mean of 47 weeks (range 13-90 weeks), with regular measurements until removal of persisting lesions at 12 months. Fifteen lesions disappeared and 56 had the classical histology of fibroadenoma, mean size 2.5 cm; 30 of the latter continued to grow throughout the study. Cytology is essential to exclude malignancy if conservative treatment is considered, and is helpful in identifying a benign lesion. A period longer than 12 months may be required for resolution of a fibroadenoma and removal under local anaesthesia as a day case offers a simple alternative.
The aim of this study was to assess upper limb morbidity following treatment for operable breast cancer. Patients were randomized to either mastectomy and axillary clearance (40 women: 12 with axillary nodal metastasis and 28 without axillary metastasis) or mastectomy and axillary sampling (54 women). Adjuvant radiotherapy was delivered to those in whom the sample revealed axillary nodal metastasis (28 women) but not to those with no axillary nodal metastasis (26 women). A subjective assessment of the state of the arm was made using a standard questionnaire. Objective assessment included upper and forearm circumference, should joint mobility and assessment of power in the pectoralis muscle. The mean age was 56.8 years (range 33-77 years) and the mean elapsed time from treatment was 5.72 years (range 4.0-7.5 years). Subjective limb oedema was greatest in those who had axillary lymph node metastasis but there was no objective difference. Subjective joint mobility was reduced in the women who received radiotherapy and this was confirmed by objective assessment (P less than 0.05). The objective reduction in arm mobility was related to the treatment rather than the axillary lymph node status. There was no difference in power. In this study women receiving adjuvant radiotherapy had significantly reduced shoulder mobility. This may have implications for current conservation studies using adjuvant radiotherapy.
Forty-three patients with large (greater than or equal to 4 cm) but operable carcinoma of the breast have been treated by endocrine manipulation before definitive local surgery. This has allowed the study of the relationship between response to therapy and pretreatment oestrogen receptor (ER) concentration, as measured by a dextran-coated charcoal adsorption method. Premenopausal patients (17) were treated by surgical (4) or medical (13) oophorectomy. Post-menopausal patients (26) received either tamoxifen (10) or an aromatase inhibitor (16). Response was assessed from statistical analysis of the changes in tumour size. On completion of 12 weeks of endocrine therapy, there was significant regression of tumour size in 18 of the 43 patients. All 18 patients had tumours with ER concentrations of greater than or equal to 20 fmol mg-1 cytosol protein. Conversely all patients except one progressing on treatment had tumours with ER concentrations of less than 20 fmol mg-1 cytosol protein. This relationship applied for both premenopausal and post-menopausal patients. The overall response rate of patients with tumours of ER concentration greater than or equal to 20 fmol mg-1 cytosol protein was 60%.
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Tumour and blood leucocyte DNA from a consecutive series of patients with primary breast cancer was probed to detect deletions at six polymorphic loci in tumour tissue. The highest frequency of allele loss (61%) was found with the probe YNZ22, which detects a sequence on the short arm of chromosome 17 (at p13.3). The previously reported loss of alleles at the Harvey ras locus (11p14) in about 20% of breast tumours was confirmed. The putative breast tumour suppressor gene on 17p may be the same as that already noted for colon and lung cancers and it is suggested that deletion of this gene is one of a cumulative series of lesions involving genetic changes in the evolution of breast cancer. The findings identify chromosome 17p as a candidate region for linkage studies in breast cancer families.
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A total of 98 breast aspirates from patients with breast cancer have been fixed and stained for oestrogen receptors using the Abbott ERICA kit. In a preliminary series of 41 aspirates, cytochemical staining index (% cells staining x mean intensity) related to the receptor concentration determined biochemically on a subsequent biopsy with a correlation coefficient of +0.65. In a second series of 56 aspirates examined after lysis and cytocentrifugation, the correlation coefficient was +0.73. For 14 patients, the response of the primary tumour to endocrine therapy was assessed objectively by serial clinical and mammographic measurements (Forrest et al., 1986) and was found to relate strongly to the cytochemical staining of the initial aspirate. The potential and limitations of this technique are discussed.
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Forty women presenting with mammillary fistulas over a 6 year period have been reviewed. The events preceding the fistula were incision of a periareolar breast abscess (n = 24), breast biopsy (n = 13) and spontaneous discharge of an inflammatory mass (n = 3). Only two of the women with abscesses were lactating. Two patients had granulomatous mastitis. The remaining 36 patients were all considered to have periductal mastitis/mammary duct ectasia as the cause of their fistulas. The two mammillary fistulas associated with lactation healed spontaneously. Nine patients had the fistula excised and the wound packed; this resulted in satisfactory healing in all but one patient. Twenty-one patients had excision of the fistula and primary closure, without antibiotic cover, but only ten healed without complications and six patients required further surgical procedures for a recurrent fistula. Six patients had primary excision and closure under antibiotic cover with a penicillin and metronidazole; all healed. Mammillary fistulas are complications of the periductal mastitis/duct ectasia syndrome. They should be treated by excision and primary closure under appropriate antibiotic cover or alternatively excised and left open to granulate.
The prognostic significance of the tumour activities of 2 steroid receptors, those for oestrogen (ER) and for progestogen (PgR), has been studied in 372 patients with breast cancer, in whom follow-up was available for 2-6 years (median 41 months). Of 252 patients with operable disease, 75.8 per cent had ER-positive tumours and 46.4 per cent had PgR-positive tumours, though a small additional fraction (6.3 per cent) had an equivocal PgR assay result. For the 236 patients with unequivocal receptor status, the relationships between disease-free interval or overall survival and receptor activity and other factors were evaluated by univariate and multivariate analyses. The latter revealed that only tumour size, node status, menstrual status and ER status related significantly to both disease-free interval and survival, though adjuvant therapy also related to disease-free interval, and tumour grade related to survival. It is concluded that measurements of PgR activity do not add to the prognostic significance of ER status.
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Cellular DNA was analysed by flow cytometry in fine needles aspirates (FNA) from both benign and malignant breast lesions in order to determine the feasibility of flow cytometric analysis. In 22 of 26 (84%) benign and 69 of 74 (93%) malignant aspirates, sufficient cells were present to produce good quality DNA histograms. DNA in all 22 benign lesions was diploid. In contrast, of the 69 cancers with sufficient cells for analysis, 40.6% had a diploid DNA content alone, whilst 59.4% had an additional DNA aneuploid line. These results indicate that the majority of FNAs provide sufficient material for flow cytometric analysis of DNA profiles. Such aspirates taken in a sequential manner may also prove to be an ideal method of studying tumour response to therapy.