Tumour grade on core biopsy and evidence of axillary involvement on ultrasound predicts response in elderly co-morbid patients treated with primary hormone therapy for oestrogen receptor positive breast carcinoma.

INTRODUCTION: Treatment of women with oestrogen-receptor positive breast cancer who are high risk for general anaesthetic remains controversial. Current guidance is based on studies pre-dating aromatase inhibitors (AIs) which may have also included hormone-receptor negative patients. Such studies have demonstrated improved disease-free survival and local disease control following surgery when compared with primary hormone therapy (PHT) alone. However uncertainty persists regarding benefit of surgery over optimal hormone treatment in patients with significant co-morbidity. METHOD: Retrospective cohort study comparing efficacy of PHT in oestrogen-receptor positive breast cancer patients considered unsuitable for surgery. Co-morbidity was scored retrospectively using the Charlson Index. Overall survival and disease specific survival were noted and multivariate analysis performed to identify predictors of treatment failure. RESULTS: 106 patients treated for breast cancer at Southampton University Hospital with PHT without surgery were identified (Mean age 84.1 years, range 48-101). 94.3% had a probability of 10 year survival of 2.25% or less according to the age-weighted Charlson score. Kaplan-Meier analysis demonstrated a four-year survival of 30% and breast cancer specific survival of 60%. Cox proportional hazards model demonstrated high-grade disease (grade III vs. grade I/II: HR = 2.007; 95% Confidence Interval (CI) = 1.004-4.014. P = 0.049) and ultrasound axillary staging (indeterminate/definite lymphatic involvement vs. no involvement: HR = 1.944; 95% CI = 1.010-3.742. P = 0.047) independently predicted early failure of PHT. CONCLUSION: A high proportion of elderly and comorbid patients die with breast cancer rather than from breast cancer. Elderly comorbid patients who initially respond to primary hormone therapy have a less than 30% incidence of delayed treatment failure during their life time; however patients with grade III disease or an abnormal axillary ultrasound are twice as likely to fail first choice PHT.

The influence of clinicopathological features on the predictive accuracy of conventional breast imaging in determining the extent of screen-detected high-grade pure ductal carcinoma in situ.

INTRODUCTION: The extent of calcified ductal carcinoma in situ (DCIS) detected by screening mammography is a determinant for treatment with breast conserving surgery (BCS). However, DCIS may be uncalcified and almost a quarter of patients with DCIS treated initially by BCS either require a second operation or are found to have unexpected invasive disease following surgery. Identification of these cases might guide selective implementation of additional diagnostic procedures. METHODS: A retrospective review of patients with a preoperative diagnosis of pure high-grade DCIS at the Southampton and Salisbury Breast Screening Unit over a ten-year period was carried out. Mammograms were reviewed independently by a consultant radiologist and additional factors including the Breast Imaging Reporting and Data System (BI-RADS(®)) breast density score, DCIS extent and disease location within the breast recorded. RESULTS: Unexpected invasive disease was found in 35 of 144 patients (24%). Within our unit the re-excision rate for all screen-detected DCIS is currently 23% but for patients included in this study with high-grade DCIS the re-excision rate was 39% (34/87). The extent of DCIS (p=0.008) and lack of expression of the oestrogen receptor (ER) predicted the requirement for re-excision in both univariate (p=0.004) and multivariate analysis (p=0.005). CONCLUSIONS: High-grade DCIS may be focally uncalcified, leading to underestimation of disease extent, which might be related to ER status. Invasive foci associated with high-grade DCIS are often mammographically occult. Exploration of additional biomarkers and targeted use of further diagnostic techniques may improve the preoperative staging of DCIS.

Screen detected sclerosing lymphocytic lobulitis and amyloid of the breast in the same patient--a possible causal link.

Sclerosing lymphocytic lobulitis (SLL) and amyloidosis of the breast are both rare. We report the case of a 59 year old woman who presented with suspicious microcalcifications on routine screening mammography. Wire-guided excision biopsy showed features typical of SLL but also localised amyloid deposits within the specimen. Amyloidosis and SLL may have similar immunological causes. This patient represents the first documented association of these two disorders.

Improving the sensitivity of stereotactic core biopsy to diagnose ductal carcinoma in situ of the breast: a mathematical model.

Stereotactic core biopsy (SCB) is performed on mammographically suspicious, non-palpable lesions of the breast. Reported sensitivities of SCB for the detection of ductal carcinoma in situ (DCIS) vary from 41% to 93%. We have developed a simple mathematical model to predict the probability of retrieving at least one diagnostic core from a focus of DCIS. We make recommendations of the number of samples needed for different sized areas of microcalcification. The sensitivity of SCB is affected by needle placement accuracy, diameter of the area of microcalcification (d), histological density of DCIS (x) (calculated as 7.5% by previous studies) and number of core samples (n) removed. The probability of achieving at least one representative core sufficient for diagnosis (P(core)) is defined as: P(core) = 1-(1 + p ([1- (x/100)]d - 1 ))n, where rho is the probability of a SCB accurately targeting the area of microcalcification. At least seven core samples should be removed in small foci (<5 mm) of DCIS to achieve a 0.75 probability of an accurate diagnosis. The probability of a diagnostic biopsy of larger areas of DCIS (>10 mm) is 0.95 when five cores are removed. This formula serves as an explanation to patients why SCB may fail to diagnose DCIS, and justifies the retrieval of more core samples to increase the probability of an accurate diagnosis and to reduce the chance of a non-representative core. In the absence of sufficient samples, a wire-guided open biopsy is necessary to exclude DCIS.

Might patients benefit from oral iron therapy following operative treatment of breast carcinoma?

AIMS: To assess the changes in blood haemoglobin concentration and serum iron indices as a consequence of breast operations for cancer in our unit. METHODS: Haematological parameters were measured in 109 patients undergoing definitive operative treatment for breast carcinoma. RESULTS: A mean fall in haemoglobin of 2.1 g (P=0.001) occurred in patients undergoing mastectomy and axillary clearance and of 1.3 g (P<0.001) in patients undergoing wide local excision and axillary clearance. The transferrin saturation (serum iron/total iron binding capacity) in both sets of patients after surgery fell on average to levels that would be expected to impair subsequent red cell production. CONCLUSION: The changes in iron indices that occurred were unrelated to the degree of blood loss consistent with a possible inflammatory effect of the operation. Oral iron therapy is unlikely to be of benefit to operative breast patients if they have normal pre-operative iron stores.

A comparison of 5-day and 8-day drainage following mastectomy and axillary clearance.

AIMS: Mastectomy and axillary clearance are standard operations for the treatment of breast carcinoma. Drainage of the mastectomy site and axilla is often required to allow accumulating blood and inflammatory fluids to escape. However, there is a lack of data relating to how long suction drains should stay in situ after major breast surgery. In our study we have tried to address this deficit by comparing the efficacy of 5-day post-operative drainage with 8-day post-operative drainage. METHODS: Patients requiring mastectomy and axillary clearance were randomized to having drains removed on day 5 or day 8 post-operatively. The number of lymphoceles, aspirations and total aspiration volumes in chest and axillary drains were compared. RESULTS: From a total of 121 patients enrolled into the study, 64 patients were randomized to the 5-day group and 57 to the 8-day group. There were significant differences regarding the number of aspirations and total aspiration volumes in chest and axillary drains between the two groups, favouring 8-day drainage. However the number of lymphoceles drained in the 5-day group was significantly higher than the 8-day group. CONCLUSIONS: Five-day post-operative drainage is as safe as 8-day post-operative drainage in the management of patients undergoing major breast surgery, but results in an increase in lymphocele aspiration and aspiration volume.

The role and histological classification of needle core biopsy in comparison with fine needle aspiration cytology in the preoperative assessment of impalpable breast lesions.

AIMS: To investigate the role of needle core biopsy (NCB) in the preoperative assessment of impalpable breast lesions, mainly derived from the NHS Breast Screening Programme (NHSBSP) and to assess our own modifications to a suggested system for the classification of breast NCBs. METHODS: The NCB, fine needle aspiration cytology (FNAC), and radiology scores from 298 women with non-palpable breast lesions presenting between January 1997 and December 1998, together with the open biopsy results (where available) were collated and analysed. RESULTS: The mean follow up period was 15.8 months (range, 5-28). The 298 NCB specimens were categorised as follows: unsatisfactory/non-representative (B1; n = 61; 20.5%), benign but uncertain whether representative (B2r; n = 52; 17.4%), benign (B2; n = 103; 34.6%), lesions possibly associated with malignancy but essentially benign (B3a; n = 9; 3.0%), atypical epithelial proliferations (B3b; n = 10; 3.4%), suspicious of malignancy (B4; n = 7; 2.3%), and malignant (B5; n = 56; 18.7%). Excision biopsy was performed in 43 cases within the B1 (n = 19), B2r (n = 8), B2 (n = 8), and the B3a (n = 8; data unavailable in one case) categories, revealing malignancy in 18 (42.8%) cases and in 65 cases within the B3b, B4, and B5 categories, revealing malignancy in 64 cases (98.5%). The sensitivity of NCB for malignancy was 87.7%, with a specificity and positive predictive value of 99.3% and 98.5%, respectively. FNAC had an inadequacy rate of 58.7%, a complete sensitivity of 34.5% and a specificity of 47.6%. CONCLUSIONS: This study confirms the value of NCB in the preoperative assessment of impalpable breast lesions. Two new categories are suggested for the NCB classification; category B2r for benign breast tissue where representativeness is uncertain, and the subdivision of category B3 into B3a for benign lesions potentially associated with malignancy (for example, radial scars and intraduct papillomas) and B3b for more worrisome atypical epithelial proliferations. These will aid the accurate audit of NCB and identify more clearly the intellectual pathway leading to a particular assessment.

Clinical outcome and bromodeoxyuridine-derived proliferation indices in 75 invasive breast carcinomas.

INTRODUCTION: In vivo labelling of human breast tumours with bromodeoxyuridine (BrdUrd) and analysis by flow cytometry (FCM) allows the labelling index (LI), S phase duration (t(s)) and the potential doubling time (t(pot)) of the tumour to be estimated. METHODS: The data for a series of tumour specimens from 75 patients with invasive breast carcinoma were reported in 1991, correlated with their lymph-node status, tumour size and grade. RESULTS AND CONCLUSIONS: This study reports the follow-up data over 10 years in respect of time to recurrence and death from the disease. There were no significant correlations between proliferation data and outcome measures. No adverse events were identified which could be attributed to the use of the halogenated pyrimidine label in vivo.

Papillary carcinoma-in-situ of the breast presenting as a fungating lesion.

We report a case of papillary breast carcinoma-in-situ which presented as a fungating lesion. To our knowledge this is the first such case to be reported in the English language literature.

Antibiotic prophylaxis for post-operative wound infection in clean elective breast surgery.

Antibiotic prophylaxis has been used to good effect in the prevention of post-operative wound infections in patients undergoing gastrointestinal operations. We have assessed the use of a single dose of intravenous antibiotic (Augmentin 1.2 g), given with induction of anaesthesia as prophylaxis, against post-operative wound infection in women undergoing clean, elective breast surgery. Three hundred and thirty-four patients were recruited. Of the 164 receiving antibiotic prophylaxis 29 (17.7%) had wound infections compared with 32 (18.8%) in the placebo group (P=0.79). There were no significant differences in any other post-operative infective complications. Antibiotic prophylaxis is probably not required in clean, elective breast surgery.

Primary non-Hodgkin's lymphoma of the female breast masquerading as a breast abscess.

We report the case of a primary non-Hodgkin's lymphoma of the breast, masquerading as a breast abscess.

How to draw the skin ellipse for a mastectomy.

The size of the skin ellipse for a mastectomy varies between patients and the accurate marking and tailoring of the skin flaps is often learnt by the surgical trainee only with increasing experience. Within the Breast Unit, a mathematical model was calculated to predict the required width of the skin ellipse for a successful mastectomy. Measurements of the straight-line distance from mid-clavicular point to the infra-mammary fold and maximum vertical height of the nipple above the infra-mammary fold were taken with the patient relaxed and supine. A close correlation (r = 0.85) was noted. Further analysis demonstrated a linear relationship between the pre-operative height to which the nipple could be suspended above the infra-mammary fold and the required maximum skin ellipse width (r = 0.87, P < 0.001). This linear relationship is easy to remember and is a useful check to ensure that the skin flaps intended will be just right. This same technique may be applicable to skin ellipses elsewhere.

Analysis of somatostatin receptor subtype mRNA expression in human breast cancer.

Somatostatin is a widely distributed inhibitory peptide with growth-inhibitory effects in several human tumours, including breast cancer, raising the possibility that it may have therapeutic potential. The effects of somatostatin are mediated via a family of cell-surface receptors that differ in their tissue distribution, pharmacological properties and intracellular response mediators, suggesting that they mediate different functions of the peptide. We have analysed the expression of somatostatin receptor subtype (SSTR1-5) mRNA in normal and malignant breast tissue. Receptor expression was analysed by reverse transcription-polymerase chain reaction (RT-PCR) using receptor subtype-specific primers and by in situ hybridization (ISH) with riboprobes synthesized by in vitro transcription of cloned PCR products. A total of 51 breast carcinomas, 36 samples of matched normal tissue, two axillary node metastases and eight normal/benign breast tissue samples were analysed. SSTR2 expression was ubiquitous in both normal and malignant breast tissue. Expression of SSTR5 was detected in approximately one-third of tumour and normal tissue, but fewer than 13% of all tissues expressed SSTR1, 3 and 4. These data suggest that SSTR2 gene expression is ubiquitous in breast cancer. Although this is unlikely to have diagnostic or prognostic significance, SSTR2-specific somatostatin analogues may have therapeutic potential in breast cancer.

Patterns of clinical metastasis in breast cancer: an analysis of 100 patients.

Many patients diagnosed with breast cancer will develop metastases and these have diverse presentations. We have reviewed 100 consecutive patients who have died with metastatic breast cancer, to determine the frequency, sites and mode of presentation of recurrent disease. The commonest site of failure was loco-regional (n = 61), this usually presented with a mass, but a minority of patients also complained of pain. Bone metastases developed in 60 patients and produced bone pain, pathological fracture (n = 6) or cord compression (n = 5). Pulmonary metastases producing shortness of breath were diagnosed in 34 patients and were asymptomatic in a further 10. Intra-abdominal metastases were found at some time in 23 patients, most commonly in the liver (n = 20) and the majority complained of epigastric pain (n = 17). Brain metastases occurred in 23 patients and produced a wide range of symptoms including those of a space-occupying lesion (n = 10), cranial nerve palsy (n = 7), diabetes insipidus (n = 3), focal limb weakness (n = 2) and meningitis (n = 1). Three patients had choroid metastases producing reduced visual acuity. Recurrent breast carcinoma can present in a variety of ways, therefore any new symptom or sign should be considered to represent recurrence until proved otherwise.

Management of ductal carcinoma in situ of the breast.

The advent of mammographic breast screening has increased the detection of ductal carcinoma in situ (DCIS), which now accounts for 15-20% of all breast cancer. While symptomatic DCIS has been treated satisfactorily by mastectomy, this may be an overtreatment of smaller screen-detected lesions. Although local excision, with or without radiotherapy, is associated with a significant risk of local recurrence of DCIS or invasive cancer, salvage surgery is usually successful. The long-term breast-specific mortality rate of treatment by mastectomy and local excision are similar. Whereas mastectomy is still appropriate for women with lesions > 30 mm in diameter or centrally placed and for those women who demand the best possible disease-free survival, local surgery should otherwise be considered.

Management of fibroadenoma of the breast.

Fibroadenoma is a common cause of discrete breast lumps in young women. There is agreement that fibroadenomas can be diagnosed preoperatively with a high degree of confidence and that some of the lesions thus diagnosed will resolve, possibly obviating the need for excision. There is, however, wide disagreement over the proportion of fibroadenomas that resolve spontaneously and therefore the benefit that accrues from an expectant policy. The aim of this study was to audit the management of fibroadenomas on one unit and clarify their natural history over a 5-year period. A cohort of 70 women with 87 fibroadenomas diagnosed using a triple assessment of clinical examination, cytology and imaging (sonomammography) have been followed for a minimum of 5 years. In all, 53 of the 'fibroadenomas' have been excised. In four cases the histology revealed benign disease other than fibroadenoma; there were no neoplasms. The sensitivity of cytology and sonomammography for the diagnosis of fibroadenoma were 84% and 98% respectively. Thirty-four fibroadenomas have not been excised. Of 25 fibroadenomas that have been reassessed after at least 5 years of follow-up, 13 (52%) have reduced in size, 4 (16%) are unchanged in size and 8 (32%) have grown. No patient has developed a carcinoma at the site of the presumed fibroadenoma. This study confirms that an expectant management policy of fibroadenomas has not resulted in misdiagnosis of carcinomas. Further, since a significant proportion of fibroadenomas remain static or reduce in size over a 5-year period many women can avoid excision.

Cystic carcinoma of the breast: a trap for the unwary.

Cystic breast masses are a common presentation to breast clinics. While the majority of cysts can be managed by simple aspiration, a small proportion are malignant. Histology records for a 10-year period have been examined to identify patients with cystic breast carcinomas. In all, 31 patients were identified. Of these, 18 had cystic degeneration of high-grade tumours, while 13 had intracystic papillary carcinoma. Both of these tumour types were diagnosed by a combination of cyst fluid cytology and breast imaging. The prognosis of high-grade tumours was poor, while that of intracystic papillary carcinomas was excellent. After cyst aspiration, bloodstained fluid should be sent for cytology and breast imaging arranged in all patients. Patients in whom a cyst refills within 2 week of aspiration require a careful re-evaluation. Cysts in postmenopausal women should be viewed with suspicion. Excision should be performed in patients with positive cytology or imaging.

Prospective study of outcome in women presenting with nipple discharge.

In this study, 56 women who presented to the breast clinic with nipple discharge have been reviewed. Patients were selected for surgery by a triple assessment of clinical examination, discharge cytology and breast imaging. Surgical intervention was required in 17 women. Significant pathology was found in 11 cases including five with carcinoma (in situ or invasive). Those women who did not have carcinoma detected at their initial presentation have been reviewed after a minimum of 5 years. None has gone on to develop breast cancer. We conclude that women with nipple discharge, but no positive findings on triple assessment, are not at an increased risk of the development of carcinoma. In addition, nipple discharge spontaneously resolves in 73% of women over a 5 year period.