Variations in steroid receptors and cyclic AMP binding proteins across human breast cancers: Evidence for heterogenity

Summary 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 (<20 fmol mg-' 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). Following 3 months of systemic therapy (6 months when patients received both endocrine and cytotoxic therapies), patients proceeded on to mastectomy and axillary lymphnode clearance. When residual tumour was present within the mastectomy specimen, a portion was selected for ER assay by the pathologist.In both pre-and post-treatment specimens, a section was cut from the face of the tissue portion used for receptor analysis, fixed in formol-saline and stained with haematoxylin and eosin to permit histopathological confirmation of the presence of tumour. Twenty-six patients in whom either the pre-or post-treatment specimen contained <10% tumour, as assessed by the pathologist, have been excluded from the Correspondence: R.A. Hawkins.

Section: Discussionmentioning

confidence: 86%

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

Hawkins¹,

Tesdale²,

Anderson³

et al. 1990

“…In view of the heterogeneity of breast tumours with respect to oestrogen receptor concentration (e.g. Braunsberg et al, 1975;Hawkins et al, 1977;Senbanjo et al, 1986), it may not be possible to attain a better correlation between assays on aspirates and those on excision biopsies.…”

Section: Patientsmentioning

confidence: 99%

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

Hawkins

Sangster²,

Tesdale³

et al. 1988

Summary 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.The presence of oestrogen receptors within a breast tumour is now established as an index of both improved prognosis and increased likelihood of response to endocrine therapy (Hawkins, 1985). The generation of monoclonal antibodies against the human oestrogen receptor (Greene et al., 1980) has permitted the development of commercial kits for both biochemical (ER-EIA) and histochemical (ER-ICA) assays by Abbott Laboratories. The results of the latter technique have been shown to correlate well with those of established biochemical, steroid-binding (DCC) methods on biopsies of solid tumour (King et al., 1985;McLelland & Coombes, 1985;McCarty et al., 1985;Hawkins et al., 1986) and the technique has recently been extended to the assessment of receptor status in breast cancer cells collected by needle aspiration (McLelland & Coombes, 1985;Flowers et al., 1985;McLelland et al., 1987;Cavailles et al., 1987;Weintraub et al., 1987). We set out to examine the feasibility of using such a method and to compare the results of the technique with (a) those of our standard DCC assay on solid biopsy, established 15 years ago and (b) response to endocrine therapy in patients with large primary tumours. Methods and materials PatientsAspirates were taken from patients presenting to the departmental clinic for the first time. The patients' ages ranged from 33 to 76 years. Aspirates were obtained by making approximately 10 passes through the tumour using a 21 gauge needle, mainly by two of us (PAL, EDCA). After preparation of smears for diagnostic cytopathology, residual material was used for fixation and cytochemical staining. In one subset of 14 patients with large tumours (>4cm, T2/T3 and one T4), the patient proceeded after aspiration to wedge biopsy for further biochemical and histological investigations prior to initiating endocrine therapy. The response of the primary tumour was monitored objectively by sequential clinical and mammographic measurements (Forrest et al., 1986). Of these patients, five received the LHRH agonist Zoladex (ICI 118630), five aminoglutethimide, two 4-hydroxyandrostenedione and two tamoxifen. One patient was premenopausal, 12 were postmenopausal and one was male. Response was classed as regress...

“…Determinations are quantitative and our unpublished data indicate that valid results may be obtained from tumours stored in liquid N2 for up to 5 years. Only small amounts of material (100-200 mg) are required for assay, although tumour heterogeneity may dictate that representative samples are taken, particularly in large cancers (Senbanjo et al, 1986). …”

mentioning

confidence: 99%

Cyclic AMP binding proteins and prognosis in breast cancer

Miller

Elton²,

Dixon³

et al. 1990