Volume-outcome relationship for adrenalectomy: analysis of an administrative dataset for the Getting It Right First Time Programme.

BACKGROUND: A minimum volume threshold of at least six procedures per annum per surgeon has been set in UK and European guidelines for adrenal surgery. The aim of this study was to investigate outcomes for adrenal surgery in England relative to annual surgeon and hospital trust volume. METHODS: Data were extracted from the Hospital Episodes Statistics database for England. A 6-year period (January 2013 to December 2018 inclusive) for all adult admissions for unilateral adrenal surgery was used. The primary outcome measure was an emergency readmission within 30 days of discharge following surgery. Procedures were categorized as open or minimally invasive surgery for analysis. Multilevel modelling was used to adjust for hierarchy and potential confounders. RESULTS: Data for 4189 adrenalectomies were identified. Only one third of surgeons (who operated on just over a half of all patients) performed at least six procedures in the year prior to the index procedure. For open surgery, emergency readmission rates fell significantly from 15.2 to 6.4 per cent for surgeons and from 13.2 to 6.1 per cent for trusts between the lowest- and highest-volume categories. Significant, but less dramatic falls were also seen for minimally invasive surgery. CONCLUSION: A volume-outcome effect was identified for adrenal surgery in England. Minimum volume thresholds should be set, although these may need to be more ambitious than the current threshold if outcomes are to be optimized. LAY SUMMARY: Surgery for disease of the adrenal gland can be complex. In many cases the skill and experience of the surgeon and the wider surgical team is thought to be important in determining the success of the procedure. The relative rarity of adrenal surgery means that there is little evidence to support this view. This study looked at outcomes for all 4189 patients who underwent adrenal surgery in England over a 6-year period. There was evidence that outcomes were better for patents when the surgeon and hospital trust had performed a larger number of adrenal surgery procedures in the year prior to the procedure. This was, however, dependent on which patient outcomes were studied and the type of procedure. These findings will inform the ongoing debate as to whether adrenal surgery in England should only be performed in regional centres by experienced teams.

Surgery for disease of the adrenal gland can be complex. In many cases the skill and experience of the surgeon and the wider surgical team is thought to be important in determining the success of the procedure. The relative rarity of adrenal surgery means that there is little evidence to support this view. This study looked at outcomes for all 4189 patients who underwent adrenal surgery in England over a 6-year period. There was evidence that outcomes were better for patents when the surgeon and hospital trust had performed a larger number of adrenal surgery procedures in the year prior to the procedure. This was, however, dependent on which patient outcomes were studied and the type of procedure. These findings will inform the ongoing debate as to whether adrenal surgery in England should only be performed in regional centres by experienced teams.

PRIMARY HYPERPARATHYROIDISM - STRATEGY FOR MULTIGLAND DISEASE IN THE ERA OF SPECT-CT.

PURPOSE: To re-examine our clinical practice and review strategy for treatment of primary hyperparathyroidism in patients with multigland disease. METHODS: Retrospective analysis of 121 consecutive primary hyperparathyroidism (PHPT) patients who underwent surgery in a tertiary center between January 2010 and December 2014. RESULTS: Of 121 patients with PHPT 87% had single gland adenoma (SGD) and 13% had multigland disease (MGD). The overall cure rate was 95.86%. MGD was more frequent in younger persons (<40y)(50% vs. 13.2%). All patients had SPECT-CT (Single Proton Emission Computerized Tomography) with 28% being SPECT-CT negative. Patients with MGD had a higher rate of persistent disease (13.33% vs. 2.83%). Specimen weight was <600mg in 75% of MGD patients. 67% of SPECT-CT negative patients had mild hypercalcemia (Calcium <2.75 mmol/L) which was more frequent in MGD patients (43% vs. 19%). CONCLUSIONS: MGD patients were more likely SPECT-CT negative (40% vs. 25.4%) and benefit from bilateral neck exploration (BNE) (74%). However, most SPECT-CT negative patients still have a single adenoma. In our series MGD was more frequent in younger patients, more likely SPECT-CT negative, often associated with mild hypercalcemia and had a higher persistence rate than SGD. BNE is the operation of choice in young, SPECT-CT negative patients. If ultrasound parathyroids suggests a single large adenoma, minimally invasive parathyroidectomy with intraoperative PTH monitoring can be considered.

RETROSTERNAL GOITRES: A PRACTICAL CLASSIFICATION.

BACKGROUND: There is no standard definition for goitres extending below the thoracic inlet and no clear guidelines for pre-operative planning of surgery. The aim of this study is a practical classification of retrosternal goitres (RSG) based on the anatomical , radiological shape and size of the thyroid. METHODS: Retrospective analysis of all thyroidectomies performed in a referral centre between January 2012 and December 2016. Patients with RSGs had a pre-operative CT scan of neck/thorax. Imaging was reviewed to establish features to predict the difficulty of delivering the goitre through the neck incision and to advise the best surgical approach. RESULTS: 847 thyroidectomies were performed with n=98 involving RSGs. TypeA (n=47) are RSG with a shape of a "cone" or pyramid with the apex pointing down. Cervicotomy is the usual approach. TypeB (n=39) are goitres with a shape of a "pyramid' with the apex pointing up, cervicotomy with ± manubriotomy or sternotomy ± thoracotomy maybe required. TypeC (n=6) are thyroid enlargements in the mediastinum connected by a pedicle with the thyroid in the neck. A cervical approach ± manubriotomy or sternotomy ± thoracotomy is needed. TypeD (n=6) are true intrathoracic or "forgotten" goitres. Sternotomy is indicated for thyroids in the anterior mediastinum though a thoracic approach for those located in the posterior mediastinum might be needed. CONCLUSION: The shape and size of goitres is important in carefully planning surgery. CT imaging with cross-sectional reconstruction should be analysed before operation. The proposed classification helps treatment planning and allows comparison of outcomes by anatomical complexity.

Serial MRI scans help in assessing early response to neoadjuvant chemotherapy and tailoring breast cancer treatment.

BACKGROUND: Tailoring neoadjuvant chemotherapy (NAC) during breast cancer treatment is performed to improve overall tumour response, with increasing evidence to support its role. This study evaluates our breast unit's experience in MRI assessment of tumour response as an aid in tailoring NAC. MATERIALS AND METHODS: This is a retrospective study of patients treated with NAC for breast cancer between 2005 and 2009 who underwent MRI to assess tumour response. Response to NAC was monitored before NAC and after 2 and/or 4 cycles of anthracycline and cyclophosphamide (AC) chemotherapy. Taxane was substituted for AC if MRI response was deemed inadequate. Tumour response on last MRI was correlated with final pathology against different tumour subtypes and in inflammatory tumours. Strength of agreement was measured using Kappa analysis. Potential predictive factors for MRI response were assessed for significance. RESULTS: 166 tumours were assessed with serial MRI scans. MRI showed high sensitivity rate (93.1%) in predicting response to NAC particularly for tumours showing partial (PR) or complete (CR) response on pathology (p < 0.001) with fair agreement on Kappa analysis (K = 0.31). MRI seems more accurate in triple negative, HR+/HER2+ and high-grade tumours. Early identification of non-responders on MRI resulted in early tailoring of NAC, with improved rates of tumour response seen in 74.2% following switching NAC. Logistic regression showed that PR or CR observed on MRI after 2 NAC cycles significantly predicted pCR (p < 0.001). CONCLUSION: Serial MRI can be used to assess patterns of tumour response to NAC. This study shows that tailoring NAC according to pattern of response can improve overall tumour response rates.

A COMPARATIVE ANALYSIS OF THE INITIAL EAST EUROPEAN CENTER EXPERIENCE WITH A WESTERN HIGH-VOLUME CENTER FOR OPEN MINIMALLY INVASIVE PARATHYROIDECTOMY (OMIP) AS TREATMENT OF PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: To compare results of treatment of primary hyperparathyroidism (PHPT) in two teaching hospitals (eastern and western Europe) and to establish conclusions regarding quality of surgery for PHPT in Romania. METHODS: We reviewed two prospectively collected databases of patients submitted to open minimally invasive parathyroidectomy (OMIP) for symptomatic PHPT in two centers from Romania and the United Kingdom (UK). We included patients with biochemically proven PHPT and positive pre-operative localization studies. We excluded patients with negative localization studies, suspected multiglandular disease, concomitant thyroid disorders and chronic renal failure. RESULTS: 60 patients were included, 27 in group A (Romanian cohort) and 33 in group B (UK cohort). We noted significant differences between groups in pre-operative serum calcium and phosphorus levels (p<0.5). There were no differences between groups regarding the presence of symptoms; in group A we had significantly more patients with renal calculi history (p=0.02), digestive symptoms (p=0.006) and osteitis fibrosa cystica (p=0.01). Two patients from the UK group had lithium associated hyperparathyroidism and 2 patients had genetic disease. Intraoperative parathyroid hormone measurement (ioPTH) was available only for group B and frozen sections were selectively used in both groups. Both the adenoma size and weights were significantly higher in group A. The median operative time was significantly longer in Romanian group (p=0.001); in this group we noted the single conversion to traditional cervicotomy (3.7%) from all studied patients. In group A we noted two patients (7.4%) with failed parathyroidectomy and persistent PHPT; the cure rate was 92.5% for Romanian group and 97% for the UK group. CONCLUSIONS: OMIP can be performed safe with a high cure rate in "small" volume endocrine centres with results comparable to western experienced endocrine centres. Romanian patients presented with more severe PHPT with more frequent end-organ damage, due probably to late diagnosis.

Small bowel perforation secondary to accidental dental plate ingestion.

The majority of ingested foreign bodies will pass through the gastrointestinal tract without incident, with less than 1% of cases resulting in complications. Herein we present a case of small bowel perforation secondary to the accidental ingestion of a dental plate. A diagnosis of perforation was made by CT imaging, but the exact cause could only be determined after resection of the affected bowel and histo-pathological examination. We re-iterate the importance of accurate and thorough history taking in patients with possible foreign body ingestion.

The ATAC adjuvant breast-cancer trial: six-year results of the endometrial subprotocol.

Postmenopausal women with localised, early breast cancer (n = 285) were enrolled in a prospective subprotocol of the 'arimidex, tamoxifen, alone or in combination' (ATAC) trial to assess gynaecological abnormalities arising during treatment with anastrozole (1 mg/day) or tamoxifen (20 mg/day). After 6 years' follow-up, there appeared to be non-significantly fewer endometrial abnormalities with anastrozole than with tamoxifen (12.4% vs 20.2%, odds ratio 0.52; 95% confidence intervals 0.20, 1.32; p = 0.17). The time to first endometrial abnormality was non-significantly longer for patients receiving anastrozole compared with tamoxifen (hazard ratio 0.57; 95% confidence intervals 0.26, 1.22; p = 0.15), with most abnormalities occurring within the first year of treatment. Fewer patients treated with anastrozole appeared to require medical intervention for endometrial abnormalities, compared with patients on tamoxifen. This study showed that there was no significant difference in endometrial pathology between anastrozole and tamoxifen treatment groups.

Clinical utility of ultrasound and 99mTc sestamibi SPECT/CT for preoperative localization of parathyroid adenoma in patients with primary hyperparathyroidism.

AIM: To evaluate the accuracy of ultrasound and parathyroid scintigraphy using single photon-emission computed tomography/computed tomography (SPECT/CT) for the preoperative localization of solitary parathyroid adenomas in patients with primary hyperparathyroidism who would be suitable for minimally invasive parathyroid surgery. MATERIALS AND METHODS: Retrospective study of 63 consecutive patients with biochemical evidence of primary hyperparathyroidism referred for preoperative localization of parathyroid adenoma that proceeded to surgery in the same institution. All patients underwent high-resolution ultrasound and Technetium-99m sestamibi scintigraphy with planar and SPECT/CT imaging. The accuracy of preoperative imaging was compared to surgical and histological findings as the reference standard. RESULTS: Fifty-nine patients had solitary parathyroid adenomas, three patients had multiglandular hyperplasia, and one patient had multiple parathyroid adenomas confirmed at surgery and histology. Thirty-five solitary parathyroid adenomas were identified preoperatively with ultrasound (64%) and 53 with SPECT-CT (90%). Concordant ultrasound and SPECT/CT findings were found in 35 cases (59%). An additional three adenomas were found with ultrasound alone and 18 adenomas with SPECT/CT alone. Fifty-one of the 56 adenomas localized using combined ultrasound and SPECT/CT were found at the expected sites during surgery. Combined ultrasound and SPECT/CT has an overall sensitivity of 95% and accuracy of 91% for the preoperative localization of solitary parathyroid adenomas. CONCLUSIONS: The combination of ultrasound and SPECT/CT has incremental value in accurately localizing solitary parathyroid adenomas over either technique alone, and allows selection of patients with primary hyperparathyroidism who would be suitable for minimally invasive surgery.

Patient-physician interactions during early breast-cancer treatment: results from an international online survey.

OBJECTIVE: To examine, via an international survey, the impact of positive and negative interactions on the patient-physician relationship. RESEARCH DESIGN AND METHODS: This online survey was conducted in five countries (USA, UK, Germany, Italy and France) in two populations: (1) postmenopausal women diagnosed with early breast cancer (EBC) in the past 5 years, who had undergone surgery; (2) breast-cancer physicians. The survey covered several topics: patient-physician interactions, EBC treatment options and sources of information. RESULTS: In total, 462 physicians and 600 patients responded. Most (85%) physicians considered having a good relationship with their patient the most rewarding part of their job. Although 60% of physicians were satisfied with the consultation time (average 17.9 min), 30% considered it insufficient, whilst 49% of patients would prefer more time. Patients reported that physicians were a primary source of information, with 81% indicating that trust in their physician was a vital component of their care. Many physicians (63%) felt that patients are overwhelmed by the amount of information available, but only 16% of patients felt overwhelmed. Most physicians (78%) consider that telling a patient she has EBC is easier than talking about recurrence; 44% rated talking about recurrence as the most stressful part of their job. Most physicians (91%) considered availability of clinical trial data to be crucial for building trust and 74% believed that treatments that minimise recurrence enable more positive conversations. CONCLUSIONS: Good-quality patient care extends beyond effective treatment to include good communication about therapeutic options, side effects, and the development of trust and confidence. The survey revealed some disparities in physicians' and patients' views, but demonstrated that a strong patient-physician relationship is highly valued by both. Patients need access to accurate information and adequate consultation time. Providing effective and well-tolerated treatments that minimise recurrence may help promote positive interactions.

Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations.

It is well documented that the aromatase inhibitors (AIs) are superior to tamoxifen as adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer. However, compared with tamoxifen, an elevated incidence of arthralgia has been observed during AI treatment. Concerns have been raised that AI-induced arthralgia may dissuade patients from completing their full AI treatment course, and may also deter physicians from prescribing an AI if they feel that patients may be at risk of permanent joint damage. Patient education about the possibility of experiencing arthralgia, and effective management of symptoms if they appear, are important in helping patients adhere to AI treatment, and consequently improving breast cancer outcomes. In this paper, we discuss the potential mechanisms behind AI-induced arthralgia, review the frequency with which arthralgia occurs, and propose for the first time an algorithm specifically for the treatment of AI-induced arthralgia. As with joint pain in non-breast cancer patients, a sequential approach to disease management is recommended, involving modifying the patient's lifestyle in addition to taking a stratified approach to pharmacological intervention with analgesia and anti-inflammatory medication. Knowing that joint symptoms can be managed in most patients may encourage patient-physician communication and treatment compliance.

The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: first results of the endometrial sub-protocol following 2 years of treatment.

BACKGROUND: Tamoxifen treatment results in a doubling of the risk of endometrial cancer after 1-2 years of treatment and a quadrupling after 5 years. Anastrozole, a third-generation aromatase inhibitor, with superior efficacy to tamoxifen, may also offer tolerability benefits in terms of effects on the endometrium. METHODS AND RESULTS: A sub-protocol of the ATAC trial compared the incidence/type of intrauterine changes following treatment with these agents in a subgroup of patients (n = 285) from the main trial. After 2 years anastrozole treatment, endometrial thickness remained

Steroid hormone receptor expression in male breast cancer.

AIMS: To investigate expression of the steroid hormone receptors estrogen receptor (ER)-alpha and -beta, progesterone receptor (PR) and androgen receptor (AR) in male breast cancer. METHODS: Specimens from 16 male breast cancers were immunostained for ERalpha, ERbeta, PR and AR. FINDINGS: Eighty-seven percent of tumours expressed ERalpha, 93% PR, 87% ERbeta and 87% AR. Staining for ERalpha and PR was confined exclusively to the nuclei of epithelial cells with some heterogeneity. Nuclear immunoreactivity was also observed with AR. Again this was restricted to epithelial cells but tended to be more uniform. ERbeta was seen in the nuclei of epithelial cells and also in stromal fibroblasts and lymphocytes. Analysis of serial sections revealed a similar pattern of staining with ERbeta and AR in epithelial cells. CONCLUSIONS: In addition to expression of the better known steroid receptors, ERalpha, PR and AR, we have demonstrated a high rate of expression of ERbeta in male breast cancer. This is in keeping with the generally high steroid receptor expression seen in males. However, the abundance of ERbeta expressed in this small series of male breast cancer is in contrast to female breast cancer where ERbeta expression is often reduced.

Surgical pathological second opinion in thyroid malignancy: impact on patients' management and prognosis.

OBJECTIVES: To evaluate the effect of inter-institutional surgical pathology review of thyroid cancer on patients' treatment and prognosis. METHODS: All cases referred to the Institute of Pathology at Leeds for thyroid pathology review between January 2001 and March 2003 were included. The referring pathologists reports were compared to those produced in the MDT meeting by the expert pathologist. Whenever there was disagreement a third expert opinion was sought who was blinded for both diagnoses. Effects on management and prognosis were evaluated if there was disagreement. RESULTS: Of the 66 patients reviewed, 12 (18%) had a different pathological diagnosis (kappa=0.33). Two had their diagnosis changed from malignant to benign and a further two from benign to malignant. Eight patients had their prognosis downgraded and four upgraded after histopathological review. Five patients had their management affected by the new pathological diagnosis. CONCLUSION: A second opinion of surgical pathology for thyroid tumours can result in major therapeutic and prognostic modifications. All cases of suspected thyroid cancers should be reviewed in a multidisciplinary meeting supported by pathologist with experience in thyroid pathology.

Expression of prostate specific antigen in male breast cancer.

Male breast cancer is uncommon, accounting for less than 1% of all breast cancers. Carcinoma metastatic to the male breast is also unusual, with metastatic prostatic carcinoma being among the most common primary sites from which such tumours derive. Metastatic prostatic cancer and primary breast cancer may be histologically indistinguishable without immunohistochemistry because both often infiltrate with a cribriform architecture. Distinguishing between primary and metastatic disease within the breast is important because the treatment options for each are radically different. Following a case in which metastatic prostatic disease was initially wrongly diagnosed as primary breast cancer, a small series of male breast cancers was examined for expression of prostate specific antigen (PSA) and prostatic acid phosphatase to assess the usefulness of these markers in making this distinction. Focal expression of PSA was found in one of 11 cases of male breast cancer. These results indicate that PSA should be used with caution in this context.

The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: baseline endometrial sub-protocol data on the effectiveness of transvaginal ultrasonography and diagnostic hysteroscopy.

BACKGROUND: The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial is a randomized, double-blind trial comparing anastrozole ('Arimidex'), alone or in combination with tamoxifen, relative to tamoxifen alone as 5 year adjuvant treatment for post-menopausal women with early breast cancer. Since tamoxifen is associated with endometrial pathology, the ATAC endometrial sub-protocol was initiated to establish the background prevalence of intrauterine pathology, and to assess prospectively the incidence and nature of intrauterine changes following endocrine therapy. Another aim was to provide data from which advice could be generated on the best endometrium screening method for patients receiving tamoxifen. METHODS: Patients underwent endometrial assessments at entry to the sub-protocol. The baseline investigations comprised transvaginal ultrasound scanning (TVUS), a hysteroscopy and an endometrial biopsy. RESULTS: A total of 285 gynaecologically asymptomatic women from 31 centres in 10 countries entered the endometrial sub-protocol. The mean uterine volume was 47.7 cm3. The median endometrial thickness overall was 3 mm. Twenty-four histologically confirmed, pathological changes were observed. Twenty-three pathologies were confirmed by TVUS, and 21 were identified by hysteroscopy and confirmed by histopathology. Women with or without intrauterine pathology had median endometrial thickness of 5 and 3 mm respectively. CONCLUSIONS: The presence of pathology was associated with increased endometrial thickness. The relative sensitivity and specificity of hysteroscopy and endometrial thickness for the diagnosis of endometrial pathology was comparable to other studies. If screening of the endometrium prior to treatment is appropriate, this study supports the use of an endometrial thickness of 3 mm, as assessed by TVUS, as a threshold for needing further investigation. This study demonstrates that if the endometrial thickness is >3 mm, hysteroscopy and biopsy is the optimal method of detecting intrauterine pathology in women with breast cancer who are about to commence endocrine treatment.

Sentinel lymph node biopsy in male breast cancer patients.

The concept of sentinel node biopsy has been validated for female breast cancer patients whereas, ALND remains the standard of care for male breast cancer patients with similar tumours. We evaluated the results of SLN biopsy in male breast cancer patients with clinically negative axillae. This study included all male breast cancer patients who underwent SLN biopsy between February 1998 and October 2003. All patients had negative axillae on clinical examination. All patients underwent pre-operative lymphoscintigraphy. SLN biopsy was performed using a combination of Patent blue V and 99mTc-radiolabelled colloidal albumin injected peritumourally. Nine patients, 26-79 years of age, were included in the study. Pre-operative lymphoscinitgraphy identified SLNs in all patients. Intraoperatively, SLNs were successfully localised in all patients. The mean number of SLNs encountered was 2.4. Five patients had a positive SLN, four a negative SLN. Five patients (one with a negative SLN, four with a positive SLN) had been elected pre-operatively to undergo ALND regardless of findings on SLN biopsy. ALND confirmed the SLN to be negative in one patient (false-negative rate: 0%) and three of the four patients with positive SLN(s) had additional positive nodes in the axilla. SLN biopsy accurately predicted axillary lymph node status in these five patients. These findings compare favourably with findings reported in the literature regarding SLN biopsy in female breast cancer patients. SLN biopsy accurately staged the axilla in male breast cancer patients and should be considered for axillary staging in male breast cancer patients with clinically negative axillae.

Agreement between preoperative core needle biopsy and postoperative invasive breast cancer histopathology is not dependent on the amount of clinical material obtained.

AIMS: To establish the relation between the amount of breast core needle biopsy (CNB) material examined and agreement between preoperative and postoperative histopathology parameters in invasive breast cancer. METHODS: The CNB and surgical specimen histopathology reports of 113 patients with invasive breast carcinoma were reviewed and the total amount of CNB material examined for each case was determined. Agreement was calculated for tumour type, grade, mitoses, nuclear pleomorphism, and tubule formation. Associations between the amount of CNB material and histopathology agreement before and after surgery were explored using binary logistic regression. RESULTS: Tumour type and grade agreed in 65.4% and 61.6% of cases, respectively. The components used to calculate grade--nuclear pleomorphism (57.4%), mitoses (59.4%), and tubule formation (55.6%)--agreed slightly less frequently. The proportion of cases with preoperative and postoperative assessments that agreed did not depend on the number of cores collected or the total amount of material examined. CONCLUSION: Neither tumour type and grade, nor the individual components used to calculate grade agreed consistently between the CNB and surgical specimen. The number of cores collected and the total amount of material reviewed by the pathologist does not influence the likelihood of agreement between preoperative and postoperative histopathology reports.

The ATAC adjuvant breast cancer trial in postmenopausal women: baseline endometrial subprotocol data.

OBJECTIVE: The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial is a randomised, double-blind trial comparing 'Arimidex' (anastrozole), alone or in combination with tamoxifen, relative to tamoxifen alone as a five year adjuvant treatment for postmenopausal women with early breast cancer. Because tamoxifen is associated with endometrial pathology, the ATAC endometrial subprotocol was initiated to establish the background prevalence of pathology, and to assess prospectively the incidence and nature of intrauterine changes before and following endocrine therapy. SETTING: International. POPULATION AND STUDY DESIGN: Two hundred and eighty-five women entered the subprotocol: the mean age was 60 years (range 44-80 years); 113 women (40%) had taken hormone replacement therapy prior to randomisation, and 238 women were parous (84%). The age at onset of the menopause was 32-58 years, with the majority becoming menopausal between 46 and 55 years of age. Two hundred and seventy-two women had a hysteroscopy before they commenced trial medication. Hysteroscopy was performed successfully in 265 women. In six women, failure of hysteroscopy at baseline led to withdrawal from the study. Three of the women who withdrew had a pipelle biopsy taken. Therefore, the total number of endometrial biopsies at baseline was 268. MAIN OUTCOME MEASURES: To assess the demographic characteristics of women entering the endometrial subprotocol and their hysteroscopic and histological findings before commencing trial medication. RESULTS: At hysteroscopy, there was a diagnosis of endometrial polyps in 34 women (13%), fibroids in 16 women (6%) and one case of suspicious endometrium, which was confirmed as a polyp on histology. Only 21 of the 34 polyps seen hysteroscopically were proven histologically (62% accuracy of hysteroscopy). Final histology found the prevalence of endometrial diagnostic categories as follows: 123 inactive endometrium (46%), 20 benign polyps (7%), 17 secretory endometrium (6%), 7 proliferative endometrium (3%), 3 atypical hyperplasia (2 in a polyp), 1 simple hyperplasia (in a polyp) and 1 fibroid. The remaining women had pipelle samples with insufficient tissue obtained, indicating a normal endometrial cavity. CONCLUSION: This is the first study of such size in gynaecologically asymptomatic breast cancer patients. This paper describes the findings in individual patients before any trial treatment was given. In this baseline group, 82% (219/268) of women had a normal endometrial cavity; 18% (49/268) had endometrial activity (proliferative or secretory endometrium in 9%) or an intracavity abnormality (hyperplasia, polyps and a fibroid in 9%). In total, 36% of biopsies had insufficient tissue for diagnosis, which in combination with a normal hysteroscopy was classed as normal. The appearance of a polyp hysteroscopically in this group was not proven histologically in approximately 40% of cases. The development of uterine pathology over time in the ATAC study will subsequently be assessed against the findings of this baseline paper.