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P A Levack

Publications and source records attributed to P A Levack.

6 recordsLinked to original sources

Does the oestrogen receptor concentration of a breast cancer change during systemic therapy?

The effect of systemic therapy on tumour oestrogen receptor (ER) concentration has been studied in 88 patients with large, operable, primary tumours (total 89) of the breast. In 26 patients, tumour was not available for study on one occasion (usually post-treatment). Forty-five patients were treated initially by endocrine therapy but, of these, 13 who had failed to respond went on to receive chemotherapy also. Seventeen patients with low concentrations of ER (less than 20 fmol mg-1 protein) were treated directly by chemotherapy. Patients underwent an incisional biopsy for confirmation of diagnosis and determination of pre-treatment ER by radioligand binding assay, followed by systemic therapy for 3 months (or 6 months for both endocrine and cytotoxic therapies). Response was assessed clinically and mammographically before mastectomy. ER concentration was then determined in the post-treatment tumour specimen. No significant change in ER concentration was seen in any treatment group except when the patients had received tamoxifen; there, receptor concentration fell to very low levels, presumably due to interference with the assay. There was no relationship between tumour response to systemic treatment and change in ER concentration. It is concluded that changes in ER concentration are unlikely to play a major role in the early response of breast tumours to systemic therapy.

Adult↗

Response to endocrine manipulation and oestrogen receptor concentration in large operable primary breast cancer.

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%.

Aminoglutethimide↗

The cytochemical detection of oestrogen receptors in fine needle aspirates of breast cancer; correlation with biochemical assay and prediction of response to endocrine therapy.

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.

Adult↗

DNA analysis of breast tumour fine needle aspirates using flow cytometry.

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.

Adult↗

Role of fine needle aspiration cytology in breast cancer screening.

In a six year period up to the end of December 1985 fine needle aspiration cytology specimens of the breast were obtained from 562 apparently healthy women invited to participate in a breast cancer screening programme. Of these, 397 had a biopsy and 173 cancers were confirmed histologically. For the diagnosis of cancer, the procedure was less successful than in symptomatic cases. The main factors influencing success were the aspirator, the small size of many cancers, and the occult nature of the lesions seen only on mammography. Retrospective analysis of the figures shows that combining the results of FNA cytology in a triple assessment with physical and mammographical findings for restricted selection means that the number of benign biopsy specimens could be reduced considerably.

Biopsy, Needle↗

A human tumour model.

An approach to the management of patients with large (greater than 4 cm) operable breast cancers is described. The conventional sequence of mastectomy followed by systemic therapy is reversed, allowing accurate measurements of response to individual forms of endocrine therapy or chemotherapy. Such a method not only permits individual selection of appropriate systemic therapy, but also allows clinical response to be related to histological and biochemical tumour parameters. A response was observed in eleven of twenty-three patients to endocrine treatment and in twelve of thirteen to combination chemotherapy. In five of the latter the response was histologically complete.

Antineoplastic Combined Chemotherapy Protocols↗