Early detection of breast cancer through population-based mammographic screening in Asian women: a comparison study between screen-detected and symptomatic breast cancers.

The first nation-wide mammographic screening program in Asia, BreastScreen Singapore (BSS), was launched in Singapore in January 2002. This study compared the presentation and results of screen-detected breast cancers with symptomatic breast cancers in two affiliated high-volume institutions, one of which was an assessment centre for BSS. The medical records of patients diagnosed with primary breast cancer at the Department of General Surgery, Singapore General Hospital and the Department of Surgical Oncology, National Cancer Centre, Singapore, during the period January 2002 to December 2003 were reviewed. Clinical and pathological comparisons were made between screen-detected lesions and symptomatic lesions. Of a total of 767 cases, 640 (83.4%) were invasive carcinomas and 127 (16.6%) were ductal carcinoma in-situ (DCIS) lesions. Only 13.4% of them were screen-detected. Compared to symptomatic cancers, screen-detected lesions were of smaller size (median size 18 versus 23 mm), a lower stage (stages 0-2, 95 versus 83.2%) and histologic grade (grade 1-2, 71 versus 60%), with a higher incidence of DCIS (31.0 versus 14.3%) and had higher rates of breast conservation (45.6 versus 28.2%) (all p-values <0.05). By multivariate analysis, tumor palpability, tumor size >20 mm, nodal involvement, cerbB2 overexpression, and advanced disease stage were independent poor prognostic factors for disease-free survival, whereas nodal involvement, advanced disease, and recurrence predicted poor cancer-specific survival. However, there was no statistically significant difference in disease-free survival or cancer-specific survival between the two groups at a median follow-up of 38 months. Screening mammography has allowed the detection of smaller and hence oncologically more favorable lesions in Asian women. Although no significant survival benefit was demonstrated in our study, a longer period of follow-up is essential before the benefit of mortality reduction, as a result of mammography screening becomes evident in our population.

Clinical validation of a customized multiple signature microarray for breast cancer.

PURPOSE: Current histopathologic systems for classifying breast tumors require evaluation of multiple variables and are often associated with significant interobserver variability. Recent studies suggest that gene expression profiles may represent a promising alternative for clinical cancer classification. Here, we investigated the use of a customized microarray as a potential tool for clinical practice. EXPERIMENTAL DESIGN: We fabricated custom 188-gene microarrays containing expression signatures for three breast cancer molecular subtypes [luminal/estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2), and "basaloid"], the Nottingham prognostic index (NPI-ES), and low histologic grade (TuM1). The reliability of these multiple-signature arrays (MSA) was tested in a prospective cohort of 165 patients with primary breast cancer. RESULTS: The MSA-ER signature exhibited a high concordance of 90% with ER immunohistochemistry reported on diagnosis (P < 0.001). This remained unchanged at 89% (P < 0.001) when the immunohistochemistry was repeated using current laboratory standards. Expression of the HER2 signature showed a good correlation of 76% with HER2 fluorescence in situ hybridization (FISH; ratio > or =2.2; P < 0.001), which further improved to 89% when the ratio cutoff was raised to > or =5. A proportion of low-level FISH-amplified samples (ratio, 2.2-5) behaved comparably to FISH-negative samples by HER2 signature expression, HER2 quantitative reverse transcription-PCR, and HER2 immunohistochemistry. Luminal/ER+ tumors with high NPI-ES expression were associated with high NPI scores (P = 0.001), and luminal/ER+ TuM1-expressing tumors were significantly correlated with low histologic grade (P = 0.002) and improved survival outcome in an interim analysis (hazard ratio, 0.2; P = 0.019). CONCLUSION: The consistency of the MSA platform in an independent patient population suggests that custom microarrays could potentially function as an adjunct to standard immunohistochemistry and FISH in clinical practice.

Laparotomy for acute complications of gastrointestinal metastases from lung cancer: is it a worthwhile or futile effort?

PURPOSE: Complications of gastrointestinal tract (GIT) metastases from lung cancer are rare and the optimal management remains controversial. Whereas some authors advocate a nonoperative policy due to the poor prognosis, others recommend aggressive surgery as it offers effective palliation. The aim of this study is to present our experience with nine patients who underwent a laparotomy for complications of GIT metastases and to determine their outcome. METHODS: Between 1995 and 2005, nine patients who underwent a laparotomy for complications of pathologically proven GIT metastases secondary to lung cancer were retrospectively reviewed. RESULTS: All patients were male with a median age of 63 years (range, 40-70 years) at initial presentation. The sites of symptomatic GIT metastases include the ileum (n = 3), jejunum (n = 3), cecum (n = 1), duodenum (n = 2) and stomach (n = 2) and the patients presented with obstruction (n = 2), hemorrhage (n = 3), intussusception (n = 3) and perforation (n = 1). The median time of symptomatic GIT metastases from initial presentation was 2 months (range, 0-8 months) and the histological subtypes of the lung cancer were squamous cell carcinoma (n = 3), large cell carcinoma (n = 3), adenocarcinoma (n = 1), pleomorphic carcinoma (n = 1) and pleomorphic with adenocarcinoma (n = 1). All patients underwent an exploratory laparotomy and the definitive surgical procedure was dependent on the site and extent of disease. These included a small bowel resection with primary anastomosis (n = 5), a subtotal gastrectomy with an extended right hemicolectomy (n = 1), a gastrojejunostomy (n = 1), a right hemicolectomy (n = 1), and an ulcerectomy with under-running of ulcers (n = 1). Eight of the nine patients (89%) recovered from surgery and were then discharged from hospital at a median time of 9.5 days (range, 6-24 days). All these eight patients survived for more than 30 days and the median survival was 6 months (range, 2-13 months). Four of the 8 patients (50%) lived for more than 6 months and all eight patients died of advanced metastatic lung cancer with multiple sites of metastases at the time of death. CONCLUSION: Gastrointestinal tract metastases should always be considered in the differential diagnosis of lung cancer patients presenting with an acute abdomen. Aggressive surgical treatment is worthwhile in a selected group of patients as it provides effective palliation.

Managing breast cancer diagnosed in first trimester pregnancy: a case report.

INTRODUCTION: Breast cancer is the most common malignancy in pregnant women, occurring at a rate of about 1 in 3000 pregnancies. Unfortunately, this will sometimes occur during the first trimester of pregnancy and this situation warrants discussion of management options with regard to the mother and child, especially with the current trend of deferring child bearing to a later age. CLINICAL PICTURE: We present a 34-year-old primigravida who had a breast lump prior to confirmation of her pregnancy and received her diagnosis of invasive breast cancer at 7 weeks' amenorrhoea. The oncologic management options of this pregnant patient with breast cancer are discussed. TREATMENT: The patient eventually opted to undergo wide excision of the breast cancer with sentinel lymph node biopsy and possible axillary clearance together with termination of her pregnancy. RESULTS: The patient successfully underwent surgery for her breast cancer and was subsequently treated with adjuvant therapy as per normal protocol for a non-pregnant patient. CONCLUSION: The management of breast cancer and pregnancy occurring concurrently is a complex problem fraught with many dilemmas for both the medical team, the patient and her family. The option chosen must involve a multidisciplinary team and have full informed consent of the patient.

Recurrent phyllodes tumours of the breast: pathological features and clinical implications.

BACKGROUND: Phyllodes tumours (PT) of the breast are fibro-epithelial neoplasms that are known to recur locally in up to 19% of patients. The failure to achieve adequate surgical margins is an important risk factor for local recurrence. This, however, is a common problem as PT are clinically similar to the more common fibro-adenoma and are therefore often locally excised without any gross surgical margins. It is still debatable as to whether it is necessary to subject the patient to repeat surgery to obtain pathologically negative margins after a diagnosis of a benign or borderline PT is made. Although the majority of recurrences are histologically similar to the initial tumour, a malignant recurrence is possible. Malignant tumours can metastasize through the haematogenous route and metastases are associated with a poor prognosis as they are poorly responsive to conventional chemotherapy. METHODS: We retrospectively reviewed 37 women who presented with local recurrence over a 10-year period to the Singapore General Hospital. Data, including age at the time of diagnosis, clinical presentation, histological features, type of surgery carried out, clinical progression and characteristics of locally recurrent disease, were analysed. Comparisons were made between those with benign, borderline and malignant tumours, as well as between those who developed a malignant recurrence and those who did not. RESULTS: The mean age at the time of diagnosis was 39.6 +/- 7.4 years and the mean tumour size was 6.0 +/- 5.1 cm. A total of 22 patients were classified as having benign tumour, 9 as having borderline tumour and 6 as having malignant tumour. Tumour grade did not influence the tumour size, the adequacy of surgical margins or the time interval to local recurrence or the number of recurrences. Local recurrence occurred after a median interval of 20 months. Although malignant tumours tended to recur earlier, this was not found to be statistically significant. The majority of recurrent tumours were histologically similar to the initial tumour; however, seven patients (19%) developed a malignant recurrence from an initially benign or borderline tumour. Although these tumours were larger, recurred more frequently and within a shorter interval, no significant predictive factor was found on multivariate analysis. Distant metastasis developed only in patients with malignant tumours and accounted for all three mortalities in the study. CONCLUSIONS: It may be acceptable to use an expectant management towards benign and borderline tumours that are excised without adequate surgical margins. However, surgery for locally recurrent tumours, as well as malignant tumours, should aim to achieve adequate surgical margins to reduce the risk of local recurrence, particularly that of a malignant recurrence.

Traumatic pneumorrhachis.

Traumatic pneumorrhachis is extremely rare, and a review of the English literature has revealed only 31 reported cases. We review the cause and pathophysiology of this unique entity in trauma patients. We also discuss the significance of this entity to the trauma specialist, paying special attention to the differences between air in the subarachnoid space versus air in the epidural space.

Correlation between breast tumour size and level of axillary lymph node involvement.

OBJECTIVE: Axillary lymph node dissection (ALND) is important for prognosis but does carry certain morbidities, particularly arm lymphoedema. Our aim was to determine whether tumour size correlates with level of axillary lymph node involvement in order to minimize ALND for small tumours. METHODS: Data were collected prospectively. Patients undergoing breast cancer surgery between May and December 2002 underwent preoperative breast ultrasound to measure the size of the primary tumour. Standard ALND was performed for all patients and levels of lymph nodes were sent separately to determine extent of involvement. RESULTS: Of the 203 cases studied, 91 (44.8%) had T1 tumours (<2 cm). The incidence of level II lymph nodes in T1 tumours was 4.4% (4/91 patients). The greater the T stage, the higher the incidence of level I and II involvement (4.4% in T1, 7.1% in T2 and 36.5% in T3 tumours). No node-positive patients had isolated level II lymph node involvement. Ultrasound-determined tumour size correlated well with final histological size (p<0.0005). CONCLUSION: Based on size, 95.6% (87/91) of patients with T1 tumours did not have level II lymph node metastases, so for these patients, level I axillary dissection is adequate.