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A cross-sectional study screened lymphedema, impaired upper limb function (ULF) and quality of life (QOL) in women post-breast cancer. Women attending review appointments who had completed surgery, chemotherapy and radiotherapy, were without recurrence, and could complete questionnaires in English were invited. Medical records were reviewed and questionnaires completed: the Morbidity Screening Tool (MST), Disability of the Arm, Shoulder and Hand questionnaire (DASH), and Functional Assessment of Cancer Therapy for breast cancer QOL questionnaire (FACTB+4). The vertical perometer (400T) measured percentage upper limb volume difference (%LVD), with 10% or greater difference diagnosed as lymphedema. Of 617 participants (mean age 62.3y, SD 10.0; mean time since treatment 63.0 months, SD 46.6), sufficient questionnaire data were available for 613 and perometry data for 417. Using the MST, 21.9% self-reported impaired ULF, 19.8% lymphedema, and 9.2% both. Based on %LVD, 26.5% had lymphedema. Histogram analysis for individuals in the first eight twelve-month intervals after treatment found impaired ULF prevalence peaked at three to five years and lymphedema at three years. Significantly worse function (DASH) and QOL (FACT B+4) resulted for those with morbidity (p

Background The aim was to determine long-term overall, breast cancer-specific and metastasis-free survival as well as axillary relapse rate from a pooled analysis of two randomized trials in women with operable breast cancer. These trials compared axillary node sampling (ANS), combined with axillary radiotherapy (AXRT) if the sampled nodes were involved, with axillary node clearance (ANC). Methods Data from two clinical trials at the Edinburgh Breast Unit that randomized patients between 1980 and 1995 were pooled. Long-term survival was analysed using Kaplan–Meier curves and Cox regression, with separate analyses for patients with node-positive (ANS + AXRT versus ANC) and node-negative (ANS versus ANC) disease. Results Of 855 women randomized, 799 were included in the present analysis after a median follow-up of 19·4 years. Some 301 patients (37·7 per cent) had node-positive disease. There was no evidence of a breast cancer survival advantage for ANS versus ANC in patients with node-negative disease (hazard ratio (HR) 0·88, 95 per cent c.i. 0·58 to 1·34; P = 0·557), or for ANS + AXRT versus ANC in those with node-positive breast cancer (HR 1·07, 0·77 to 1·50; P = 0·688). There was no metastasis-free survival advantage for ANS versus ANC in patients with node-negative tumours (HR 1·03, 0·70 to 1·51; P = 0·877), or ANS + AXRT versus ANC in those with node-positive disease (HR 1·03, 0·75 to 1·43; P = 0·847). Node-negative patients who underwent ANS had a higher risk of axillary recurrence than those who had ANC (HR 3·53, 1·29 to 9·63; P = 0·014). Similarly, among women with node-positive tumours, the risk of axillary recurrence was greater after ANS + AXRT than ANC (HR 2·64, 1·00 to 6·95; P = 0·049). Conclusion Despite a higher rate of axillary recurrence with ANS combined with radiotherapy to the axilla, ANC did not improve overall, breast cancer-specific or metastasis-free survival. Axillary recurrence is thus not a satisfactory endpoint when comparing axillary treatments.

Purpose To investigate conventional prognostic factors for ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), and survival after breast-conserving therapy (BCT) in screen-detected and symptomatic cases on surveillance up to 25 years. Patients and Methods A total of 1812 consecutive patients in three cohorts (1981–1989, 1990–1992, and 1993–1998) with T12N01M0 invasive breast cancer were treated with BCT (median follow-up, 14 years). Tumor type and grade were reviewed by a single pathologist. Hormone receptor status was measured by immunohistochemistry on tissue microarrays. A Cox proportional hazards model was used to assess independent prognostic variables for relapse and survival. Results A total of 205 IBTR occurred, with 5-, 10-, 15-, and 20-year actuarial relapse rates of 4.5% (95% confidence interval [CI] 3.35–5.5%), 8.4% (95% CI 7.1–9.8%), 14.1% (95% CI 12.0–16%), and 17.4% (95% CI 14.5–20.2%). Number of nodes, young age, pathologic tumor size, and multifocality were significant factors for IBTR. Three hundred seventy-eight patients developed DM. The actuarial metastatic rate was 12% at 5 years and 17.9% at 10 years. Young age, number of positive nodes, pathologic tumor size, and tumor grade were significant factors for DM relapse. When conventional prognostic indices were taken into account screen-detected cancers showed no improvement in overall relapse or survival rate compared with symptomatic cases but did show a reduced risk of DM after IBTR. After 10 years IBTR relapse continued at a constant rate of 0.87% per annum. Conclusions The Edinburgh BCT series has shown that screen-detected invasive breast cancers do not have significantly different clinical outcomes compared with symptomatic cases when pathologic risk factors are taken into account. This suggests that these patients be managed in a similar way.

The SRC family of ER co-regulators are frequently overexpressed in breast cancer. Overexpression of AIB1 appears to be linked to hormone resistance in HER2 positive breast cancer. However, the role of these co-regulators in ER negative disease is poorly understood. SRC1, SRC2 and AIB1 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate tumours that overexpress both HER2 and AIB1 were associated with markedly reduced relapse free, distant relapse free and overall survival compared to HER2 and AIB1 only overexpressing tumours irrespective of ER status. In ER negative disease both SRC1 and AIB1 were linked to early relapse and death. The SRC family of ER co-regulators is involved in early relapse and resistance in both ER negative and ER positive breast cancer challenging the conventional concept that this effect is mediated solely via the ER.

Aims: To assess the validity of grading in the Edinburgh Breast Conservation Series; a consecutive cohort of 1812 early breast cancer patients treated by breast conservation and radiotherapy between 1981 and 1998 in a single specialist centre with ≥9 years’ follow-up and full staging data. Methods and results: A single pathologist (J.St.J.T) graded 1650 cases using the Elston and Ellis method (EE) with particular reference to the component data: acinar differentiation, nuclear pleomorphism and mitotic counts. The original method was then compared with binary scoring of the same components and the relationship to prognosis reassessed. EE grades and individual grade components were prognostic (P

Aims: Frozen section histology of lymph nodes intraoperatively is associated with a false negative rate of twenty-five per cent. Imprint cytology is reported to have greater accuracy than frozen section. Accurate intraoperative examination of lymph nodes could help to prevent some patients from having a second axillary operation in breast cancer. This study assesses the sensitivity of imprint cytology to lymph node metastases using two different staining techniques. Methods: Imprint cytology of 238 freshly excised axillary lymph nodes in 53 patients with stage T1-2, N0, M0 breast cancer was performed. Imprints were stained using toluidine blue dye and anti-pancytokeratin immunoglobulin to compare the two staining methods. A consultant histopathologist blinded to the routine histology results examined each set of imprints. A non-pathologist also examined each set of imprints to determine whether a technician could be used to screen slides in order to decrease the workload of the pathologist. Results: Sensitivity was 82% with toluidine blue and 36.4% with anti-pancytokeratin immunoglobulin. Positive predictive values were 100% and 57% respectively for toluidine blue and anti-pancytokeratin. The false-negative rate was 18% for toluidine blue and 63.6% for anti-pancytokeratin antibody when examined by a consultant histopathologist. Conclusions: Imprint cytology using toluidine blue is as sensitive as frozen section in the detection of axillary lymph node metastases. A positive result may be acted upon with acceptable safety. Immunohistochemistry using antibody to pancytokeratin did not improve imprint sensitivity in this study. Imprint cytology could help to prevent a second operation in 80% of breast cancer patients with positive lymph nodes.

Background In the treatment of operable breast cancer by breast conservation, the extent of axillary dissection, the need for radiotherapy to the axilla and the morbidity associated with these procedures have not been assessed adequately. Methods Patients with operable breast cancer were randomized to have level III axillary node clearance (232 patients) or axillary node sample (234 patients). Radiotherapy to the axilla was given selectively. Radiotherapy was not given to those who had an axillary clearance. In the early part of the study all patients who had node sample were treated by radiotherapy (54 patients); subsequently this was modified to include only those who were node positive. The morbidity to the shoulder and arm was assessed before and after operation by measuring upper limb volume and circumference, and combined glenohumeral and scapular movement and muscle power. Results Comparing the two surgical policies, no difference was found in local (axillary clearance 14 versus sample 15), axillary (eight versus seven) or distant (29 versus 29) recurrence. There was no statistically significant difference in 5-year survival rate (clearance 82·1 versus sample 88·6 per cent). Morbidity was least in those who had a node sample and no radiotherapy to the axilla. Radiotherapy to the axilla in patients who had a node sample resulted in a significant reduction in range of movement of the shoulder, e.g. mean(s.e.) 2·2(0·6) cm reduction in lateral rotation at 3 years. Surgical axillary clearance was associated with significant lymphoedema of the upper limb, e.g. 4·1(0·7) per cent increase in arm volume at 3 years. Conclusion A selective policy for the management of the axilla is associated with no increase in axillary recurrence or mortality rate compared with routine axillary node clearance. Patients who are node negative after axillary sample can avoid radiotherapy or axillary clearance.

The expression of MIB-1, a marker of proliferation, has been measured in tumours from 61 patients with large (>4 cm) operable breast cancers (T2,3 N0,1M,) treated with primary systemic therapy; either with hormone therapy (27 patients), chemotherapy (17 patients) or hormone therapy followed by chemotherapy (17 patients), in order to determine its role in predicting response and survival. Staining was variable between tumours (1–89% of malignant cells staining). There was no correlation between MIB-1 expression and oestrogen receptor concentration when both parameters were measured as a continuous variable, but MIB-1 values were significantly lower in ER-rich tumours compared with tumours which were ER-poor. Response to hormone treatment was restricted to oestrogen receptor positive tumours. Tumours which responded to treatment also had significantly lower MIB-1 values than those which did not (P< 0.004). In terms of response to chemotherapy, neither ER status or MIB-1 predicted for response. However, MIB-1 values were significantly higher in tumours proceeding to a complete pathological response as compared to those with a lesser degree of response (P< 0.01). The overall survival of patients at 10 years was 50%. Neither ER status or MIB-1 predicted for survival following primary hormone therapy. However, MIB-1 predicted for survival following primary chemotherapy; the survival of patients with tumours which showed high MIB-1 expression was significantly better than the survival of those patients with tumours which showed low MIB-1 expression (P< 0.003). In contrast, in the group of patients treated with chemotherapy after failed hormone therapy, survival was significantly worse in those with high MIB-1 expression (P< 0.005).

Molecular and immunohistochemical studies of genetic events on chromosome 17p were prospectively compared with conventional clinical and pathological parameters and disease behaviour at a minimum of 72 months follow-up. In a series of 91 patients with primary operable breast cancer, 37 out of 91 (41%) patients had disease relapse and 23 out of 91 (25%) had died during the follow-up period. Allelic imbalance at the YNZ22 locus (17p13.3), demonstrated in 33 out of 63 (52%) informative patients, was significantly associated with disease recurrence (P < 0.01, 2 d.f. Cox analysis) and showed a trend towards impaired survival (P = 0.08, 2 d.f. Cox analysis) after a mean follow-up of 84 months for survivors. By contrast, p53 mutation (in 10 out of 60, 17% of cancers), p53 allelic imbalance (in 23 out of 56, 41% informative patients), p53 mRNA expression (in 47 out of 87, 54% patients), p53 mRNA overexpression (in 24 out of 87, 28%) or p53 protein expression (detected in 25/76, 32%) were not associated with disease behaviour. There was no significant association between allelic imbalance at YNZ22 and any abnormality of p53 DNA, RNA or protein. Allelic imbalance at 17p13.3 (YNZ22) serves as a marker of poor prognosis in breast cancer. As yet unidentified genes on 17p13.3, distinct from and telomeric to p53, are therefore likely to be of clinical importance in breast cancer.

Four hundred and seventy-five women with silicone breast implants were matched with control groups and reviewed for evidence of breast cancer. No increased risk of developing breast cancer was found in women who had received a silicone breast prosthesis following breast augmentation compared with the expected incidence in this age group. In women who had a breast reconstruction using a silicone breast implant following mastectomy for breast cancer, there was no increased rate of recurrence, either locally, regionally or at distant sites, or a decrease in survival compared with matched controls.

This study aimed to investigate lymphedema prevalence using three different measurement/diagnostic criterion combinations and explore the relationship between lymphedema and quality of life for each, to provide evaluation of rehabilitation. Cross-sectional data from 617 women attending review appointments after completing surgery, chemotherapy, and radiotherapy included the Morbidity Screening Tool (MST; criterion: yes to lymphedema); Lymphedema and Breast Cancer Questionnaire (LBCQ; criterion: yes to heaviness and/or swelling); percentage limb volume difference (perometer: %LVD; criterion: 10%+ difference); and the Functional Assessment of Cancer Therapy breast cancer-specific quality of life tool (FACT B+4). Perometry measurements were conducted in a clinic room. Between 341 and 577 participants provided sufficient data for each analysis, with mean age varying from 60 to 62 (SD 9.95–10.03) and median months after treatment from 49 to 51. Lymphedema prevalence varied from 26.2% for perometry %LVD to 20.5% for the MST and 23.9% for the LBCQ; differences were not significant. Limits of agreement analysis between %LVD and the subjective measures showed little consistency, while moderate consistency resulted between the subjective measures. Quality of life differed significantly for women with and without lymphedema only when subjective measurements were used. Results suggest that subjective and objective tools investigate different aspects of lymphedema.

Current treatments for metastatic breast cancer are not associated with significant survival benefits despite response rates of over 50%. High-dose therapy with autologous bone marrow transplantation (ABMT) has been investigated, particularly in North America, and prolonged survival in up to 25% of women has been reported, but with a significant treatment-related mortality. However, in patients with haematological malignancies undergoing autologous transplantation, haematopoietic reconstruction is significantly quicker and mortality lower than with ABMT, when peripheral blood progenitor cells (PBPCs) are used. In 32 women with metastatic breast cancer, we investigated the feasibility of PBPC mobilisation with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) after 12 weeks' infusional induction chemotherapy and the subsequent efficacy of the haematopoietic reconstitution after conditioning with melphalan and either etoposide or thiotepa. PBPC mobilisation was successful in 28/32 (88%) patients, and there was a rapid post-transplantation haematopoietic recovery: median time to neutrophils > 0.5 x 10(9) l-1 was 14 days and to platelets > 20 x 10(9) l-1 was 10 days. There was no procedure-related mortality, and the major morbidity was mucositis (WHO grade 3-4) in 18/32 patients (56%). In a patient group of which the majority had very poor prognostic features, the median survival from start of induction chemotherapy was 15 months. Thus, PBPC mobilisation and support of high-dose chemotherapy is feasible after infusional induction chemotherapy for patients with metastatic breast cancer, although the optimum drug combination has not yet been determined.

In 215 patients with operable breast cancer (T1-T3, N0-1, M0) and no other or previous cancer, presenting to a single breast unit, sufficient tumour was available for the prospective determination of four putative biochemical markers of prognosis: oestrogen receptor (ER) activity, cathepsin D (cath D), epidermal growth factor receptor (EGFR) activity and cyclic AMP-binding proteins (c-AMP-b). There were significant inter-relationships between ER and EGFR (r = -0.26), c-AMP-b and cath D (r = +0.32) and ER and c-AMP-b (r = +0.14). After follow-up (median 36.2 months), a total of 55 recurrences (18 locoregional only) and 35 deaths were recorded. By univariate analysis, up to 10 of 18 biochemical, clinical and histopathological variables of potential prognostic value were significantly related to disease-free interval or death, but by multivariate analysis only oestrogen receptor concentration and node status contributed significantly to risk of both distant recurrence/death; in addition, tumour size made a small contribution to the risk for a distant recurrence only. Only two parameters, tumour grade and ER concentration, were significantly related to risk of locoregional recurrence by univariate analysis, but by multivariate analysis, only tumour grade was important. It is concluded that tumour ER concentration, axillary nodal status and tumour grade remain as the most important prognostic factors in the early years after presentation of operable breast cancer, with a minor influence of tumour size. At this time, the prognostic significance of quantitative measurements of ER concentration, carefully controlled for the quality of both assay and tumour specimen, is probably greater than is generally appreciated. We have yet to identify other factors, which add significantly to the short-term prognostic value of these key features.

Summary Pre-operative and postoperative upper limb volume, limb circumference and shoulder girdle mobility were measured in 121 consecutive patients who had a conservation approach for breast cancer. Axillary management comprised (i) axillary node sampling ( n =28), or (ii) axillary node sampling plus regional radiotherapy ( n = 61 ), or (iii) axillary node clearance (levels I, II and III) ( n =19) or (iv) axillary node dissection (levels I and II) plus regional radiotherapy ( n =13). Upper limb volume on the treated side increased significantly ( P ) for both groups (i) and (ii). Upper limb circumference was significantly greater after more extensive axillary surgery ((iii) and (iv)) than for node sampling ((i) or (ii)) ( P = 0.006 ). Upper limb volume increased by over 200 ml in 39 patients (32%). Axillary radiotherapy (groups (ii) and (iv)) significantly reduced shoulder girdle mobility ( P ). The combination of axillary node dissection and radiotherapy carried the highest morbidity. This study demonstrates that upper limb morbidity at 1 year following breast conservation reflects the extent of axillary surgery and the use of axillary irradiation. Axillary node sampling, with axillary irradiation if node positive, or a level III axillary clearance are associated with similar levels of upper limb morbidity and are both appropriate options for staging and/or treating the axilla during breast conserving surgery.

Purpose: This study aimed to investigate validity of a newly developed Morbidity Screening Tool (MST) to screen for fatigue, pain, swelling (lymphedema) and arm function after breast cancer treatment. Methods: A cross-sectional study included women attending reviews after completing treatment (surgery, chemotherapy and radiotherapy), without recurrence, who could read English. They completed the MST and comparator questionnaires: Disability of the Arm, Shoulder and Hand questionnaire (DASH), Chronic Pain Grade Questionnaire (CPGQ), Lymphedema and Breast Cancer Questionnaire (LBCQ) and Functional Assessment of Cancer Therapy questionnaire with subscales for fatigue (FACT F) and breast cancer (FACT B + 4). Bilateral combined shoulder ranges of motion were compared (upward reach; hand behind back) and percentage upper limb volume difference (%LVD =/>10% diagnosed as lymphedema) measured with the vertical perometer (400T). Results: 613 of 617 participants completed questionnaires (mean age 62.3 years, SD 10.0; mean time since treatment 63.0 months, SD 46.6) and 417 completed objective testing. Morbidity prevalence was estimated as 35.8%, 21.9%, 19.8% and 34.4% for fatigue, impaired upper limb function, lymphedema and pain respectively. Comparing those self-reporting the presence or absence of each type of morbidity, statistically significant differences in comparator variables supported validity of the MST. Statistically significant correlations resulted between MST scores focussing on impact of morbidity, and comparator variables that reflect function and quality of life. Conclusion: Analysis supports the validity of all four short-forms of the MST as providing indications of both presence of morbidity and impacts on participants' lives. This may facilitate early and appropriate referral for intervention. © 2013 Elsevier Ltd. All rights reserved.

Glycogen synthase kinase 3β (GSK3β) is phosphorylated and inactivated by the phosphoinositide 3 kinase PI3K/Akt pathway. Activation of Akt phosphorylates GSK3β preventing phosphorylation of cyclin D1 which leads to accumulation and nuclear localisation of cyclin D1, activation of CDK4/6 and cell cycle progression. The CCND1 gene found at chromosome 11q13 has been shown to be amplified in approximately 15 % of breast cancers. Cyclin D1, the product of the CCND1 gene, is one of the most commonly overexpressed proteins in breast cancer. Protein expression for GSK3β, phosphorylated-GSK3β (p-GSK3β), cyclin D1 and gene expression of CCND1 were examined in tissue microarrays of 1,686 patients from the Edinburgh Breast Conservation Series. High GSK3β expression was associated with reduced distant relapse-free survival (DRFS), while no association between p-GSK3β and breast cancer-specific survival was seen. CCND1 amplification is also associated with poor DRFS. On the contrary, cyclin D1 overexpression is associated with an increase in DRFS. Multivariate analysis was performed. We suggest that analysis of both GSK3β and cyclin D1 expressions can be considered as a marker of good prognosis in early breast cancer.

Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in patients with early breast cancer. EGFR, HER2, HER3, pEGFR, pHER2 and pHER3 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully-documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate overexpression of HER2 and pHER2 to be associated with a significant reduction in overall survival (OS) (HR: 1.66, 95 % CI 1.22-2.26, p = 0.001 and HR: 1.57, 95 % CI 1.22-2.03, p = 0.001, respectively) and distant relapse-free survival (DRFS) (HR: 1.63, 95 % CI 1.23-2.18, p = 0.001 and HR: 1.55, 95 % CI 1.23-1.97, p = 0.0002, respectively). Paradoxically, expression of pEGFR was associated with a significantly improved OS (HR: 0.67 95 % CI 0.50-0.91, p = 0.01) and DRFS (HR: 0.73, 95 % CI 0.56-0.96, p = 0.025). Expression of activated EGFR/HER2 provides additional information on ER positive breast cancer patients and suggests alternative treatment for those in this subgroup.

The incidence of local recurrence (LR) after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favourable tumours. The aim of this study was to examine the effect of adjuvant therapies in tumours with excellent prognostic features.Patients with primary invasive breast cancer2 cm diameter, grade 1 or good prognosis special type, and node negative, treated by wide local excision (WLE) with clear margins were randomised into a 2 × 2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen. Trial entry was allowed to either comparison or both.The actuarial breast cancer specific survival in 1135 randomised patients at 10 years was 96%. Analysis by intention to treat showed that LR after WLE was reduced in patients randomised to radiotherapy (RT) (HR 0.37, CI 0.22-0.61 p0.001) and to tamoxifen (HR 0.33, CI 0.15 - 0.70 p0.004). Actuarial analysis of patients entered into the four-way randomisation showed that LR after WLE alone was 1.9% per annum (PA) versus 0.7% with RT alone and 0.8% with tamoxifen alone. No patient randomised to both adjuvant treatments developed LR. Analysis by treatment received showed LR at 2.2%PA for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments.Even in these patients with tumours of excellent prognosis, LR after conservative surgery without adjuvant therapy was still very high. This was reduced to a similar extent by either radiotherapy or tamoxifen but to a greater extent by the receipt of both treatments.

Introduction: Patients with early-stage breast cancer, treated with endocrine therapy, have approximately 90% 5-year disease-free survival. However, for patients at higher risk of relapse despite endocrine therapy, additional adjuvant therapy, such as chemotherapy, may be indicated. The challenge is to prospectively identify such patients. The Mammostrat (R) test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions. We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up.Methods: Tissue microarrays from a consecutive series (1981 to 1998) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review. Of 1,390 cases stained, 197 received no adjuvant hormonal or chemotherapy, 1,044 received tamoxifen only, and 149 received a combination of hormonal therapy and chemotherapy. Median age at diagnosis was 57, 71% were postmenopausal, 23.9% were node-positive and median tumor size was 1.5 cm. Samples were stained using triplicate 0.6 mm(2) tissue microarray cores, and positivity for p53, HTF9C, CEACAM5, NDRG1 and SLC7A5 was assessed. Each case was assigned a Mammostrat (R) risk score, and distant recurrence-free survival (DRFS), relapse-free survival (RFS) and overall survival (OS) were analyzed by marker positivity and risk score.Results: Increased Mammostrat (R) scores were significantly associated with reduced DRFS, RFS and OS in estrogen receptor (ER)-positive breast cancer (P < 0.00001). In multivariate analyses the risk score was independent of conventional risk factors for DRFS, RFS and OS (P < 0.05). In node-negative, tamoxifen-treated patients, 10-year recurrence rates were 7.6 +/- 1.5% in the low-risk group versus 20.0 +/- 4.4% in the high-risk group. Further, exploratory analyses revealed associations with outcome in both ER-negative and untreated patients.Conclusions: This is the fifth independent study providing evidence that Mammostrat (R) can act as an independent prognostic tool for ER-positive, tamoxifen-treated breast cancer. In addition, this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors. When viewed in the context of previous results, these data provide further support for this antibody panel as an aid to patient management in early-stage breast cancer.

A group of 66 elderly women with primary breast cancer were treated with tamoxifen and followed for a minimum of 2 years. Of these, 32 whose disease remained controlled for the 2-year period were considered to have had a ‚worthwhile‚ response, 27 in whom disease progressed were considered to have had an unsatisfactory result and seven opted for alternative treatment. By Union Internacional Contra la Cancrum (UICC) criteria, 14 women had a complete response, 20 a partial response, in five disease remained static and in 20 it progressed without response. Prediction of outcome after assessment according to UICC criteria at 3 and 6 months was unsatisfactory (19 and 34 of 59 correctly predicted respectively). Analysis of multiple tumour measurements over 12 weeks was no better (33 of 59 correctly predicted). Immunocytochemical assay of fine-needle aspirates for oestrogen receptor (ER) provided a better predictor (38 of 47 correct) and the difference in survival between patients with and without ER activity was significant (P < 0.001). Conventional assessments of response at 3 and 6 months are unsatisfactory for judging the long-term benefit to the patient. ER status is the best predictor of response and outcome.

The multistep theory of carcinogenesis predicts that the cumulative effect of the loss of key tumour suppressor genes and overexpression of important oncogenes in an individual cell will cause a normal cell to become a cancer cell. To test this theory in breast cancer, we have examined 80 breast tumours for evidence of such events using deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) extracted from breast tumour tissue. Southern blot analysis of paired blood/tumour DNA demonstrated loss of heterozygosity, and by implication tumour suppressor gene loss, at the p53 locus in 15 43 informative tumours, the apc (adenomatous polyposis coli) locus in 3 12 and the DCC (Deleted in Colon Cancer) locus in 4 12 tumours. Frequent allele losses were also detected at the putative tumour suppressor gene loci YNZ22 ( 31 54 ) and THH59 ( 9 19 ). Northern blot studies of RNA expression in the same tumours demonstrated oncogene overexpression for c-erbB-2 in 21 71 , c-myc in 21 76 and H-ras in 14 79 tumours. The genetic profile of individual tumours exhibited both tumour supressor gene loss and oncogene overexpression but there were no distinct patterns of genetic events. This study has identified tumour suppressor gene loss from five loci and overexpression of three different oncogenes in a series of breast cancers, including multiple events in single tumours, and thus presents strong evidence for the multistep theory of carcinogenesis in breast cancer.

The p53 locus on the short arm of chromosome 17 at 17p 13.1 was examined for loss of heterozygosity, mutation, mRNA and protein expression in 60 primary breast cancers. Allele loss around the p53 locus was detected in 19/45 informative tumours (42%). p53 mutations in the evolutionarily conserved exons 5 to 9 were detected in 17/60 (28%) by amplification mismatch and confirmed by direct DNA sequencing. p53 mRNA expression was detected by Northern blot in 36/59 (61%) of tumours, and p53 protein expression using antibody 1801 on frozen-tissue sections in 13/44 of the tumours examined. p53 mutation was significantly associated with oestrogen-receptor-poor tumours (p less than 0.01) and hence with poor prognosis, but not with other clinical or pathological parameters. There was no statistical correlation between loss of heterozygosity around the p53 locus at 17p13.1 and p53 mutation. Furthermore, p53 mutation was not associated with p53 expression detected by immunohistochemical staining with antibody 1801 or as p53 mRNA. In addition, events on 17p (allele losses, p53 mutation, p53 expression) were independent of c-erbB-2 expression. In breast cancer, by contrast with colorectal, lung and ovarian cancer, there appears to be no clear association between p53 DNA abnormalities and p53 expression.

Twenty-four evaluable patients with stage T4 breast cancer were entered into a phase II study and received chemotherapy comprising cyclophosphamide 1,000 mg m-2 i.v., doxorubicin 50 mg m-2 i.v., vincristine 1.4 mg m-2 i.v. and prednisolone 40 mg orally for 5 days, given 3 weekly for four cycles prior to undergoing loco-regional radiotherapy. All patients completed treatment as planned with no major acute toxicity from either chemotherapy or radiotherapy. Subsequently 52 patients with stage T4 breast cancer were randomised in a phase III trial to receive either radiotherapy alone (RT) or this chemotherapy and radiotherapy (CHOP + RT). A significantly higher complete response rate was achieved in the CHOP + RT treatment arm (P = 0.03). However a larger proportion of the RT arm achieved loco-regional control after salvage treatment for relapse such that 50% of the RT arm and 57% of the CHOP + RT arm had no evidence of loco-regional disease at the time of last follow-up or death. There was no statistical difference in time to distant relapse or overall survival. Analysis of the pilot study showed results comparable to the trial CHOP + RT arm. This trial suggests that this cytotoxic therapy used in conjunction with radiotherapy has only marginal value in improving prognosis in locally advanced breast cancer.

The reduction in breast cancer mortality during the past 20 years can be partly explained by increased use of adjuvant endocrine therapy. During recent years a number of studies have explored potential benefits of aromatase inhibitors (AIs) over tamoxifen for postmenopausal women with oestrogen receptor-positive breast cancer. Early results, which reported improved disease-free survival with AIs, led to a recommendation by the American Society of Clinical Oncology technology assessment panel in 2005 that the treatment of these women should include an AI, either as initial (up-front) therapy or following a period of treatment with tamoxifen [1]. Despite the improved disease-free survival with AIs, a recent review of up-front use of AIs failed to show any evidence of significant improvement in overall survival over tamoxifen, or in quality of life, and advised caution for use of this strategy pending future results from the BIG 1-98 clinical trial [2]. Professor Ian Smith presented results from BIG 1-98 comparing 5 years of letrozole with tamoxifen. These results, first presented at the San Antonio Breast Cancer Symposium in 2008 [3], show no statistically significant overall survival benefit for Letrozole at 76 months follow up. These results support a recent meta-analyses of AI use that showed no evidence of a significant overall survival advantage when AIs are used up front [4]. In fact, the only AI studies that demonstrate an overall survival advantage to date involve switching to an AI after initial therapy with tamoxifen [5]. Current American Society of Clinical Oncology guidelines, and recent National Institute of Clinical Excellence guidelines, allow clinicians to decide whether to pursue an up-front approach to AI use or whether to adopt a switching strategy. Professor Ian Smith also presented a summary of results from the Z-FAST and ZO-FAST studies, comparing the effects of zoledronic acid initiated concurrently with letrozole or when bone loss becomes clinically significant in postmenopausal women with early breast cancer. An integrated analysis of both studies [6] suggests that up-front use of zoledronic acid is an effective strategy to prevent AI-associated bone loss, when given in combination with letrozole for postmenopausal women, and in addition appears to reduce the risk of breast cancer recurrence. Although the recurrence data require further follow up, these early results would support a change in the 2009 National Institute of Clinical Excellence guidelines. Professor Mike Dixon presented data on the number of mastectomies currently performed for early breast cancer in the UK using data from the NHS Breast Screening Programme. He suggested that although the mastectomy rate for screen-detected ductal carcinoma in situ has remained fairly constant in recent years, the massive increase in the numbers of women diagnosed with ductal carcinoma in situ means that overall the number of mastectomies has increased. In his opinion, as ductal carcinoma in situ is a unifocal disease it may be possible to avoid mastectomy in a large number of cases, although increased use of oncoplastic techniques will be required for more extensive resections. Alternative strategies could include preoperative neoadjuvant hormone therapy or preoperative HER2 blockade. Finally, Professor Dixon presented a summary of the COMICE study, where patients recommended to have breast-conserving surgery were randomised to have breast magnetic resonance imaging or not. In this study, magnetic resonance imaging caused a significant increase in the mastectomy rate (13% vs. 9%) but did not reduce the re-excision rate; as a result, routine use of magnetic resonance imaging for all women having breast-conserving surgery is not currently recommended.

Eighty-eight patients presenting with operable breast cancer of 4 cm or greater in diameter (T2, T3, N0, N1, M0) have received primary systemic therapy. Response was assessed following 12 weeks of systemic therapy by linear regression analysis of changes in tumour volume. Definitive locoregional surgery (mastectomy n = 82, wide local excision n = 6) was performed on completion of systemic therapy (3-6 months). Response was observed in 24 (39%) of the 61 patients who received endocrine therapy; all 24 had tumours with an oestrogen receptor (ER) concentration of greater than or equal to 20 fmol mb-1 cytosol protein. Cytotoxic therapy was reserved for patients with tumours of ER concentration less than 20 fmol mg-1 cytosol protein (n = 27) or when endocrine therapy had failed (n = 20). Response was observed in 34 patients (72%). The overall survival rate at 3 years was 86%, with 81% remaining free from local relapse. We propose that the treatment policy outlined in this paper should now be tested against orthodox management by controlled randomised trial.

A method to determine the binding of epidermal growth factor (EGF) to the particulate fraction of the cell has been established and evaluated using rat liver, human placenta, and tumours of human breast and brain. Little EGF receptor (EGFR) activity was detected in normal or benign tumour tissues except for meningioma (positive in 95% samples), but EGFR were present in 43% of 131 breast tumours and 75% of 55 primary cerebral tumours. Despite the strong inverse correlation between EGFR activity and oestrogen receptors in breast tumours and a tendency for high levels of EGFR activity to be associated with glioblastoma multiforme, analysis showed that EGFR was of little prognostic significance in patients with tumours of either breast or brain.

The protein product of the H-ras oncogene, p21, has been measured semiquantitatively in solubilized particulate fractions of 160 primary tumours from patients presenting without evidence of distant metastatic breast cancer. Levels of p21 have then been related to factors of established prognostic significance, and to clinical outcome after primary treatment in terms of disease-free interval and survival times. p21 was detected by Western blotting in all tumour fractions, but amounts varied markedly between different tumours. There was no significant relationship between levels of p21 and the menopausal status of the patient, tumour oestrogen receptors, grade, and clinical stage. However, there was a significant trend for tumours to be associated with lymph node involvement as p21 was increasingly expressed. Elevated levels of p21 were also significantly related to early disease recurrence and death from cancer. Multivariate stepwise analysis showed that both p21 and lymph node status were independent statistically significant factors for disease recurrence and survival, and that no other parameter was significant for clinical outcome after adjustment for p21 and lymph node status. These results indicate that tumour levels of p21 are an important prognostic variable in patients with early breast cancer.

Cyclic AMP binding proteins were measured in the primary tumour from 100 patients with non-disseminated breast cancer selected on the basis that sufficient tumour material was available for analysis. These measurements have been related to factors of established prognostic value and to the patients' disease-free interval and survival. There was a wide variation in amounts of binding proteins in different tumours. Values were significantly higher (P less than 0.05) in oestrogen receptor-negative tumours but no statistically significant correlations were apparent between levels and tumour grade or whether the patients had lymph node metastasis or adjuvant treatment. However, levels were significantly higher in patients whose disease recurred within 3 years of primary treatment as compared with those who remained disease-free. Using a retrospectively determined cut off point of 8 pmol mg-1 cytosol protein, it was shown that patients with tumour cyclic AMP binding in excess of this value had a significantly greater chance of developing recurrent disease and poorer survival rates (P less than 0.001 by Cox analysis) than those with lower levels. This remained true when other prognostic factors were taken into account in a multivariate analysis. It is suggested that the level of tumour cyclic AMP binding may be an independent prognostic factor for patients with early breast cancer.

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.

Aim The TELEMAM trial aimed to assess the clinical effectiveness and costs of telemedicine in conducting breast cancer multi-disciplinary meetings (MDTs). Methods Over 12 months 473 MDT patient discussions in two district general hospitals (DGHs) were cluster randomised (2:1) to the intervention of telemedicine linkage to breast specialists in a cancer centre or to the control group of ‘in-person’ meetings. Primary endpoints were clinical effectiveness and costs. Economic analysis was based on a cost-minimisation approach. Results Levels of agreement of MDT members on a scale from 1 to 5 were high and similar in both the telemedicine and standard meetings for decision sharing (4.04 versus 4.17), consensus (4.06 versus 4.20) and confidence in the decision (4.16 versus 4.07). The threshold at which the telemedicine meetings became cheaper than standard MDTs was approximately 40 meetings per year. Conclusion Telemedicine delivered breast cancer multi-disciplinary meetings have similar clinical effectiveness to standard ‘in-person’ meetings.

Aims The sentinel node biopsy technique which is being increasingly used to stage breast cancers has limitations regarding not being able to find the blue hot node in about 5% of cases and false negative results in 7% of cases. It has been suggested this is probably due to tumour blocking the lymphatic channels. The four node sampling technique is dependent on the surgeon's ability to find abnormal palpable nodes in the axilla without visual or radioactive signal directions. We have combined the two techniques with the expectation to improve the results. Method The study evaluates the combined technique in 434 patients with early breast cancer in a single centre. Results A blue sentinel node was identified in 394 of 434 cases (91.7%), the false negative rate was 2.4%. Thirty six patients had no sentinel node identified. Thirteen of these had positive nodes in the node sample. Conclusion Axillary node sampling adds to the accuracy of the sentinel node biopsy using blue dye. Pathological features suggest that the principal cause of false negative sentinel node biopsy is due to blocking of the lymphatic channels by the cancer.

A study of 799 patients undergoing consecutive axillary node sampling performed by all grades of surgeon is discussed. The number of nodes sampled ranged from 0 to 12 with only 17 patients (2%) having less than three nodes in the specimen submitted for pathology. The mean number of nodes sampled was 4.7 and the median was 4. The percentage of patients who were node positive did not increase significantly as the number of nodes sampled increased. This study has shown that it is possible to dissect out axillary nodes consistently and that the chance of identifying involved nodes does not increase as the number of nodes sampled increases. Axillary node sampling procedures should be more widely used particularly in patients with a low probability of nodal involvement.

We surveyed the attitudes of breast cancer professionals to standard face-to-face and future telemedicine-delivered breast multidisciplinary team (MDT) meetings. Interviews, which included the Group Behaviour Inventory, were conducted face-to-face (n = 19) or by telephone (n = 26). The mean total score on the Group Behaviour Inventory was 96 (SD 19) for 33 respondents, which indicated satisfaction with standard MDT meetings, irrespective of role and base hospital. Positive attitudes to videoconferencing were more common among participants with previous experience of telemedicine (Spearman's rank correlation 0.26, P = 0.91). Common themes emerging from the interviews about telemedicine-delivered MDTs included group leadership, meeting efficiency, group interaction, group atmosphere and technical quality of communication. Most participants were satisfied with standard breast MDTs. Nurses and allied health professionals were least supportive of telemedicine.

Multidisciplinary team (MDT) meetings for decisions on cancer management are a cornerstone of UK cancer policy. We have proposed a comprehensive methodology to assess the clinical and economic effectiveness of telemedicine in this setting, which is being tested in a randomized breast cancer trial. Pre- and post-telemedicine assessment includes attitudes to and expectations of telemedicine, based on semistructured interviews. The communication content of videotapes of the MDT meeting is being scored using Borgatta's revised Interaction Process Analysis System. The technical performance of the telemedicine equipment is reported on a standardized pro forma. A short questionnaire captures key elements of professional satisfaction for each patient discussion (consensus on future management, confidence in and sharing of decision), added value of linkage, group atmosphere, overall conduct of the meeting and compliance with SIGN guidelines. A cost-minimization analysis will be used for economic assessment.

A prospective study of 14225 patients has been undertaken to determine the inter-relationship between periductal mastitis and duct ectasia and to establish whether there is an association between smoking and either of these two conditions. Periductal mastitis affected women at a younger age than did duct ectasia. Of 139 patients with the clinical syndrome of periductal mastitis, 97 (70 per cent) had a past history of previous periductal mastitis, compared with only one (1 per cent) of 186 patients with the clinical syndrome of duct ectasia (P< 0·0001). There was a significant excess of smokers in patients with clinically (124 (89 per cent) of 139) and pathologically (71 (91 per cent) of 78) diagnosed periductal mastitis compared with age-matched controls (both P< 0·001), but there was no such excess in those with clinically (52 (28 per cent) of 186) or pathologically (15 (23 per cent) of 64) diagnosed duct ectasia. These data suggest that periductal mastitis and duct ectasia are separate conditions which affect different age groups, have different aetiologies, and should now be considered as separate entities.

Twenty patients with cyclical breast pain were enrolled in a double-blind cross-over trial in which either a soy protein drink or a flavoured cow's milk was taken orally each day for 3 months before crossing over to the alternate drink for a further 3 months. Records of pain scores were taken throughout the study. Blood was also taken before and after 3 and 6 months for the measurement of phytoestrogents to assess compliance. Two women withdrew from the study at the outset leaving 18 evaluable patients who completed the study. Of these 10 (56%) felt that soy protein improved breast pain (two of whom received soy as first treatment) and two (11%) felt that cow's milk alleviated symptoms (one receiving this as first preparation) and the remaining six (33%) experienced no relief of pain with either dietary preparation. Blood levels of diadzein and genistein were elevated after the ingestion of soy protein in only 13 patients (seven of whom felt that soy improved their breast pain); in the remaining five patients (three of whom suggested that soy protein improved breast pain) phytoestrogen levels were no higher than pretreatment values. Although the ingestion of soy protein may be associated with relief of breast pain, these results illustrate the problem of non-specific effects in studies of mastalgia in that 1) cow's milk also relieved breast pain in some patients and 2) that the benefits of soy protein were not always associated with evidence of elevated circulating levels of phyto-estrogens, indicating the difficulty of compliance in dietary intervention studies using soy foods.

Aims: There are no uniformly agreed guidelines regarding the treatment of local breast cancer in patients who have stable metastatic disease. The aim of this study was to define the role of breast surgery in the management of stage IV disease by reviewing the clinical outcome in patients with stage IV disease submitted to surgery in a regional breast cancer unit. Methods: All patients who underwent breast surgery from 1993 to 1999 and had known metastatic disease or who were diagnosed with metastases within one month of surgery were identified and their clinical outcome was studied using death and local recurrence as end points. Results: Median survival after breast surgery was 23 months. Ten of the 20 patients were alive with no local disease at 20 months mean follow-up. Three of 10 patients who died developed local recurrence and had local disease at the time of death. Conclusion: The local surgery does have a role in controlling the primary cancer and controlling local symptoms in a selected group of patients with stable metastatic disease.

In a consecutive series of 73 patients undergoing a level III axillary clearance, interpectoral nodes were sought and, if palpable, excised. 18 interpectoral nodes were identified in 15 patients, 10 (14%) of whom had involved and 5 of whom had uninvolved interpectoral nodes. 7 of the 10 patients with involved interpectoral nodes also had axillary node involvement, but 3 patients had positive interpectoral nodes in the absence of involved axillary nodes. A comparison of patient and tumour characteristics in the groups of patients with and without interpectoral node involvement showed that patients who had involved interpectoral nodes were significantly younger and had significantly larger tumours. Interpectoral node involvement by breast cancer is not uncommon and these nodes can be involved in the absence of axillary nodal involvement. They should be looked for, and if identified, excised during axillary clearance.

In 1990, 215 patients with operable breast cancer were entered into a prospective study of the prognostic significance of five biochemical markers and 15 other factors (pathological/chronological/patient). After a median follow-up of 6.6 years, there were 77 recurrences and 77 deaths (59 breast cancer-related). By univariate analysis, patient outcome related significantly to 13 factors. By multivariate analysis, the most important of nine independent factors were: number of nodes involved, steroid receptors (for oestrogen or progestogen), age, clinical or pathological tumour size and grade. Receptors and grade exerted their influence only in the first 3 years. Progestogen receptors (immunohistochemical) and oestrogen receptors (biochemical) were of similar prognostic significance. The two receptors were correlated (r=+0.50, P=0.001) and displaced each other from the analytical model but some evidence for the additivity of their prognostic values was seen when their levels were discordant. British Journal of Cancer (2002) 87, 8–14. doi:10.1038/sj.bjc.6600335 www.bjcancer.com © 2002 Cancer Research UK

A retrospective study found that a breast screening clinic generated fewer localization biopsies for non-palpable mammographic abnormalities than a symptomatic clinic (3.36 versus 9.89 per 1000 mammograms, respectively) and that a greater proportion of such biopsies were malignant. This study determined the reason for this difference. There were 108 of 304 (35.5 per cent) and 17 of 130 (13.1 per cent) carcinomas in women attending the screening and breast clinics respectively (relative risk 2.72 (95 per cent confidence interval 1.70–4.34)). This difference was regardless of age. The characteristics of the mammographic abnormality, the Wolfe pattern, a family history of breast carcinoma, parity and age at first pregnancy were similar in both groups. Women attending the screening clinic were referred for localization biopsy after assessment by clinicians and radiologists at a joint clinic; there was no joint assessment for patients attending the breast clinic. The same staff attended both clinics, although the proportion of time spent at each varied. This study suggests that all women with a non-palpable mammographic abnormality should be reviewed at a joint assessment clinic before localization biopsy is recommended.

Expression of pS2, an oestrogen-regulated gene, has been associated with a good short-term prognosis and response to endocrine therapy. The aim of this study was to determine whether expression of mRNA for the pS2 gene in breast cancer could contribute useful information on disease behaviour and survival at medium-term follow-up. Northern blotting was used to detect pS2 messenger ribonucleic acid (mRNA) in the primary tumour tissue from each of 90 patients with breast cancer. Axillary node status was established by sampling or clearance, oestrogen receptor concentration by enzyme immunosorbant assay and follow-up was continued for at least 6 years or until death. At 83 months mean follow-up, 29 of 90 (32%) patients had recurrent disease and, of these, 18 (20%) had died from breast cancer. pS2 mRNA expression, present in 26 of 90 (29%) cancers, was associated with freedom from disease recurrence (P = 0.026) and was significantly associated with survival at a minimum of 6 years follow-up (P < 0.001). Pathological node status and tumour size were also significantly associated with disease recurrence (P < 0.001 and P = 0.002 respectively) and inversely with survival (P < 0.001 and P < 0.001 respectively). After multiple Cox regression analysis, pS2 expression was still a significant predictor of recurrence (but not survival) after adjusting for node status and tumour size; oestrogen receptor was an independent predictor of survival. The combination of node status and pS2 expression discriminated patients with particularly good prognosis (node negative, pS2 positive: no mortality at 6 years) or poor prognosis (node positive, pS2 negative; 41% mortality at 6 years). Evaluation of pS2 expression in breast cancer at diagnosis may provide additional useful prognostic information to conventional staging. Images Figure 1

Recent worldwide press and media speculation that silicone implants may be linked to an increased incidence of breast cancer, other cancers, and connective tissue diseases-particularly systemic sclerosis-is a current cause for concern to the medical profession and public alike. We conducted a cross-sectional study of the prevalence of connective tissue diseases, as well as signs and symptoms associated with these conditions, in women who had received a silicone gel-filled breast implant for either breast augmentation or breast reconstruction following mastectomy for breast cancer compared with women without implants in South East Scotland. We compared 317 patients who had had a silicone gel-filled breast implant inserted with matched controls. We found no increased incidence of antinuclear antibodies or rheumatoid factor in the study groups. We detected one case of rheumatoid arthritis in the reconstruction group and one in matched controls, but no cases of any other connective tissue disease. No cases were found among the augmentation patients or their controls. No differences were found in symptoms or physical signs of connective tissue diseases between the study patients and their controls. This study has failed to find any case for a link between silicone gel-filled breast implants and connective tissue diseases.

Between 1984 and 1990, 94 women presenting to the Edinburgh Breast Unit with operable breast cancer of 4 cm or greater in diameter (T2, T3, N0, N1, M0) were given preoperative systemic therapy. Initially, all women received hormone therapy, with CHOP (cyclophosphamide 1 g m(-2), doxorubicin 50 mg m(-2), vincristine 1.4 mg m(-2) to a maximum of 2 mg and prednisolone 40 mg per day orally for 5 days) chemotherapy being administered to those who failed to respond by 3 months. After April 1987, first-line hormone therapy was only offered to women with oestrogen receptor (ER)-moderate/-rich (> 20 fmol mg(-1) protein) tumours, and CHOP was reserved for those women whose tumours failed to respond to hormone therapy and for those with ER-negative/-poor tumours. Response data have been published previously (Anderson et al, 1991). After a median follow-up of 7.5 years, there is no difference in survival between those women given initial hormone therapy and those given chemotherapy, with neither group having yet reached its median survival. The two key factors that predicted for a poor survival were the number of involved axillary nodes after preoperative systemic therapy (P < 0.00001) and a lack of response to preoperative therapy (P < 0.05). These data suggest that many women with ER-moderate/-rich tumours will have a good prognosis after preoperative hormone therapy alone. However, it is possible to identify, by their post-systemic therapy axillary node status, a group of women who still have an appalling prognosis after preoperative chemotherapy or hormone therapy.

Because of allegations linking silicone implants with cancer and connective tissue diseases and mounting media coverage, women with silicone breast implants are extremely concerned, despite the lack of evidence showing a link between silicone gel-filled breast implants and connective tissue diseases or cancer. To assess whether or not this group of women were satisfied with their operations, we sent all women who had silicone breast implants inserted in the south-east of Scotland between 1982 and 1991 a quality of life questionnaire. One hundred and two breast augmentation and 212 breast reconstruction patients replied. Not everyone answered every question. The majority of women in our study, 84% (79/94) and 91.8% (192/209) of augmented and reconstructed patients, respectively, stated that they were satisfied with their operations, although only about half were very satisfied. Although 91.2% (270/296) of all the women were aware of the allegations with 29.7% (88/296) concerned, only 3% (9/296) of all the women felt that there was cause for concern. It would appear that, although most women with silicone breast implants are aware of the accusations regarding silicone and systemic illnesses, the adverse publicity has only given a small number of them a cause for concern and the majority are satisfied with the outcome of their operation and perceive the benefits to outweigh the risks.

Because little or no information exists about the life span of silicone implants, there is a need for a non-invasive and sensitive diagnostic tool for assessing their integrity. It is extremely difficult to diagnose rupture of these implants clinically. The aims of this study were to assess how many of our patients--in particular asymptomatic women--had ruptured implants and whether or not ultrasound was an effective tool in excluding rupture and reassuring anxious patients. All patients in the south east of Scotland who had a silicone gel-filled breast implant inserted between the years 1982-1991 were invited to take part in an investigation into morbidity due to silicone implants. We screened 307 asymptomatic patients with 385 implants and only found one patient with a ruptured silicone implant. One other patient had a ruptured saline implant and one implant was found to have leaked. We found ultrasound to be a quick, reliable, cheap and safe method of screening for implant rupture which can be used to reassure an anxious patient that her implants are intact.