R.W. Blarney

The clinical relevance of static disease (no change) category for 6 months on endocrine therapy in patients with breast cancer.

This study reports on the clinical relevance of the static disease (SD) category in 255 breast cancer patients on endocrine therapy. All patients had received first- and second-line endocrine therapy and were assessed for response by the International Union Against Cancer (UICC) criteria. We did not include patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy, e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, remained in long-term remission on first-line endocrine therapy. We analysed survival from initiation of first-line endocrine therapy by the remission criteria, i.e. complete response (CR), partial response (PR), static disease (SD) or progressive disease (PD), achieved on that therapy. Patients were divided into those with metastatic breast cancer (MBC) and non-metastatic disease. There was no significant difference in survival from starting first-line endocrine therapy between patients who obtained CR, PR or SD: all three groups of patients survived significantly longer than patients who showed PD within 6 months (all P < 0.0001 except CR versus PD [MBC] which was P < 0.002). Equally, for second-line endocrine therapy there was no difference in survival between patients who obtained CR, PR or SD: all three groups (CR, PR and SD) survived significantly longer than PD (all P < 0.0003 except for CR versus PD which was P < 0.003 for non-metastatic and P < 0.059 for MBC). Durable SD appears to be a clinically useful criteria of therapeutic remission.

Investigation of primary tamoxifen therapy for elderly patients with operable breast cancer

Abstract Tamoxifen therapy in elderly patients (> 70 years) with operable breast cancer has been investigated by two trials in our unit. The first compared tamoxifen with surgery alone: 62% patients eventually failed tamoxifen, 47% required surgery. But 37% had control of the primary tumour with tamoxifen alone for over 5 years. To identify those with a long-term response to tamoxifen a second trial included cases with high oestrogen receptor (ER) content. Patients were randomized to tamoxifen 20 mg daily ( n = 94) or mastectomy and adjuvant tamoxifen ( n = 53). Only 3% of patients initially progressed on tamoxifen, compared to 26% in the first trial. In the second trial at a median followup of 3 years, 32% of patients receiving tamoxifen had developed local relapse, but only 16% needed surgery. Patients with static disease after 6 months on tamoxifen had a significantly shorter duration of control and were more likely to require mastectomy compared to partial or complete responders. To select patients with long-term control of the primary tumour with tamoxifen we propose a two stage selection where cases with low ER are excluded, and those with static response of the primary tumour at 6 months have the tumour removed.

Short-term effects of pure anti-oestrogen ICI 182780 treatment on oestrogen receptor, epidermal growth factor receptor and transforming growth factor-alpha protein expression in human breast cancer

Expression of oestrogen receptor (ER), epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF alpha) proteins was assessed by immunocytochemistry on primary breast cancer specimens obtained before and following short-term (7-day) presurgical exposure to pure anti-oestrogen (7 alpha- [9- (4,4,5,5,5-pentafluoropentylsulphinyl) nonyl] estra-1,3,5, (10)-triene-3,17 beta-diol, ICI 182780) treatment and compared with no-treatment controls. Paired needle-core and mastectomy samples were obtained from 21 patients. Effects of ICI 182780 (10(-7)M) on MCF7 breast cancer cell ER, EGFR and TGF alpha expression were also examined over 14 days. ER protein was significantly suppressed by ICI 182780 in vivo (P = 0.009) and comparative analysis of short term ICI 182780 effects in vitro, using ER-positive MCF7 cells, gave largely equivalent results. EGFR and TGF alpha protein levels were unaltered by treatment. ICI 182780 suppresses ER without a concomitant rise in either EGFR or TGF alpha.

Intratumoural heterogeneity of proliferation in invasive breast carcinoma evaluated with MIBI antibody

The growth fraction has been assessed in 120 cases of primary operable breast carcinoma using the MIB1 antibody and an index of the cycling fraction has been derived for the periphery and the centre of different histological types of breast cancer. The mean MIB1 labelling index for each tumour showed a strong association with histological grade (P < 0.001), tumour type sub-group (P < 0.001), tumour size (P = 0.029), the presence of vascular invasion (P = 0.050) and the presence of distant metastases (P = 0.043). In addition both the peripheral (P = 0.005) and mean (P = 0.048) but not the central (P = 0.069) MIB1 labelling showed a correlation with overall survival, when those cases in the upper quartile were compared with those showing fewer cycling cells. A significantly greater MIB1 labelling index was seen at the periphery than the centre (P < 0.001). This difference in the cycling fraction was not associated with a bias in tumour grade or size. When the data were analysed according to tumour type it was seen that in invasive ductal/no special type (NST) of grades 2 and 3, tubular mixed and lobular carcinomas the peripheral index was significantly higher than the central index (P = 0.002, P = 0.003, P = 0.024 and P = 0.004 respectively). No significant difference in peripheral and central proliferation index was seen in tubular, medullary and atypical medullary or mixed NST and lobular carcinomas (P = 0.480, P = 0.089, P = 0.069 respectively). When tumours were grouped into 3 categories according to the ratio of MIB1 labelling (i.e. those with (i) relatively greater central, (ii) relatively greater peripheral and (iii) homogeneous cell cycling fractions), it was found that the central index was comparable (P = 0.243). Peripheral MIB1 immunostaining was however significantly different (P = 0.049) in the three groups. Thus, the heterogeneity in proliferation seen in this series was not apparently caused by a relative fall in proliferation in the centre of the tumour but to a relative increase in cell cycling fraction at the periphery.

Zoladex in Advanced Breast Cancer

In the treatment of 53 premenopausal patients with advanced breast cancer, the LHRH analogue, Zoladex (goserelin), produced a response rate similar to that of surgical oophorectomy. Endocrinologically, Zoladex caused castrate levels of serum oestradiol and progesterone except in a small number of patients, where intermittent, suppressed peaks of oestradiol persisted. Treatment of 34 premenopausal patients with Zoladex combined with the anti-oestrogen tamoxifen (Nolvadex) produced significantly lower levels of serum oestradiol; all patients had castrate serum oestradiol levels. It is suggested that a prospective randomised study is necessary to determine any clinical advantage from such a combination.

Ultrasound guided core biopsy of suspicious mammographic calcifications using high frequency and power Doppler ultrasound

AIM The pre-operative diagnosis of suspicious mammographic microcalcifications usually requires stereotactic needle biopsy. The aim of this study was to evaluate if high frequency 13 MHz ultrasound (HFUS) and power Doppler (PD) can aid visualization and biopsy of microcalcifications. MATERIALS AND METHODS Forty-four consecutive patients presenting with microcalcifications without associated mammographic or palpable masses were examined with HFUS and PD. Ultrasound-guided core biopsy (USCB) was performed where possible. Stereotactic biopsy was carried out when US-guided biopsy was unsuccessful. Surgery was performed if a diagnosis of malignancy was made on core biopsy or if the repeat core biopsy was non-diagnostic. RESULTS Forty-one patients (93%) had ultrasound abnormalities corresponding to mammographic calcification. USCB was performed on 37 patients. In 29/37, USCB obtained a definitive result (78.4%). USCB was non-diagnostic in 4/9 benign (44.4%) and 4/28 (14.3%) malignant lesions biopsied. The complete and absolute sensitivities for malignancy using USCB were 85.7% (24/28) and 81% (23/28), respectively. USCB correctly identified invasive disease in 12/23 (52.2%) cases. There was no significant difference in the presence of abnormal flow on PD between benign and malignant lesions. However, abnormal PD vascularity was present in 43.5% of invasive cancer and was useful in directing successful biopsy in eight cases. CONCLUSION The combination of high frequency US with PD is useful in the detection and guidance of successful needle biopsy of microcalcifications particularly where there is an invasive focus within larger areas of DCIS.