[Preoperative biopsy diagnosis in suspicion of breast cancer]. / Praeoperativ biopsidiagnostik ved mistanke om brystkraeft.

The golden standard in non-operative breast cancer diagnosis is the triple test, a combination of clinical evaluation, mammography/ultrasound and needle biopsy, either fine needle aspiration cytology (FNAC) or histological core biopsy. FNAC and core biopsy both have advantages and disadvantages but neither of them can act as a decisive diagnostic procedure on its own. The final diagnosis should always be a consensus between the three diagnostic modalities in the triple test. Quality assurance of the pathological diagnosis is a must. The number of uncertain diagnoses i.e. atypia or suspicion of malignancy should be kept at a minimum. These diagnostic categories call for additional diagnostic procedures and thereby cause a delay in reaching the final diagnosis leading to definitive treatment.

[Carcinoma in situ of the breast]. / Carcinoma in situ mammae.

Ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) represent a proliferation of malignant epithelial cells within the ducts of the breast without invasion through the basement membrane. It is assumed that all invasive carcinomas of the breast are preceded by DCIS or LCIS. However, it is not known what proportion of DCIS or LCIS--if left untreated--will progress to invasive carcinoma. Standard treatment for DCIS is breast-conserving surgery with free margins and radiation therapy. LCIS is usually treated by observation alone.

Down-regulation of the tumor suppressor protein 14-3-3sigma is a sporadic event in cancer of the breast.

14-3-3 proteins comprise a family of highly conserved and broadly expressed multifunctional regulatory proteins that are involved in various cellular processes such as cell cycle progression, cell growth, differentiation, and apoptosis. Transcriptional expression of the sigma isoform of 14-3-3 is frequently impaired in human cancers, including carcinomas of the breast, which has led to the suggestion that this protein might be involved in the neoplastic transformation of breast epithelial cells. Here we report on the analysis of 14-3-3sigma expression in primary breast tumors using a proteomic approach complemented by immunohistochemical analysis by means of specific antibodies against this isoform. We show that the levels of expression of 14-3-3sigma were similar in non-malignant breast epithelial tissue and matched malignant tissue with only sporadic loss of expression observed in 3 of the 68 tumors examined. Moreover we show that 14-3-3sigma immunoreactivity was restricted to epithelial cells and significantly stronger in the myoepithelial cells that line the mammary ducts and lobules. The lack of expression of 14-3-3sigma in the three breast carcinomas was not associated with high levels of expression of the dominant-negative transcriptional regulator DeltaNp63 or with increased expression of estrogen-responsive finger protein, a ubiquitin-protein ligase (E3) that targets 14-3-3sigma for proteolysis. Validation of the results was performed retrospectively on an independent clinical tumor sample set using a tissue microarray containing 65 primary tumors. Our data suggest that, contrary to what was previously thought, loss of expression of 14-3-3sigma protein is not a frequent event in breast tumorigenesis.

Integrating proteomic and functional genomic technologies in discovery-driven translational breast cancer research.

The application of state-of-the-art proteomics and functional genomics technologies to the study of cancer is rapidly shifting toward the analysis of clinically relevant samples derived from patients, as the ultimate aim of translational research is to bring basic discoveries closer to the bedside. Here we describe the essence of a long-term initiative undertaken by The Danish Centre for Translational Breast Cancer Research and currently underway for cancer biomarker discovery using fresh tissue biopsies and bio-fluids. The Centre is a virtual hub that brings together scientists working in various areas of basic cancer research such as cell cycle control, invasion and micro-environmental alterations, apoptosis, cell signaling, and immunology, with clinicians (oncologists, surgeons), pathologists, and epidemiologists, with the aim of understanding the molecular mechanisms underlying breast cancer progression and ultimately of improving patient survival and quality of life. The unifying concept behind our approach is the use of various experimental paradigms for the prospective analysis of clinically relevant samples obtained from the same patient, along with the systematic integration of the biological and clinical data.

[Mammographic screening in the county of Copenhagen. Clinical consequences of the first three screening rounds]. / Mammografiscreening i Københavns Kommune. Kliniske konsekvenser efter de første tre screeningsrunder.

INTRODUCTION: Service mammography has been offered biennially to women aged 50-69 years in the municipality of Copenhagen since 1991. The results were compared to breast cancer cases before initiation of screening. The comparison concerns prognostic factors and the treatment-related consequences. MATERIAL AND METHODS: Data from the Copenhagen service mammography screening were linked to data from the DBCG database. RESULTS: Before screening, 16% of breast cancer cases had a tumour size of 10 mm or less, this percentage increased to 41 in the screen-detected cases. Sixty per cent of breast cancer cases showed no evidence of metastatic spread to axillary lymph nodes before screening; this percentage increased to 78 per cent in the screen-detected cases. Forty per cent of ductal carcinomas showed a malignancy grade I before screening, compared to 53% in the screen-detected cases. Thirteen per cent were treated with breast conserving therapy before screening, as opposed to 48% in the screen-detected cases. Forty-one per cent needed postoperative adjuvant treatment before screening, compared with 21% in the screen-detected cases. DISCUSSION: A marked improvement was seen in the prognostic and treatment-related characteristics of the screen-detected breast cancer cases, as compared to breast cancer cases from the same area before screening was initiated.

[Mammography screening in the county of Copenhagen. Results of the first three screening rounds]. / Mammografiscreening i Københavns Kommune. Populationsresultater fra de første tre screeningsrunder.

INTRODUCTION: Biennial service mammography screening for breast cancer has been offered to women aged 50-69 years in the municipality of Copenhagen since 1991. We report the results of the first three invitation rounds. MATERIAL AND METHODS: Data were collected from the Copenhagen service mammography screening database and other Danish registers. RESULTS: The average participation rate during the first three invitation rounds was 66%. The breast cancer detection rate was 10/1,000 screened in the first invitation round and 5/1,000 in the consecutive rounds. The probability of a false positive mammography was 6% at the prevalent screen, and this was reduced to 3% at incidence screens. Fifty-two cases of interval cancer were seen after the first invitation round. The expected number was 152, which gives a proportional interval cancer rate of 0.34. The sensitivity was 86% and the specificity 94% after the first round. DISCUSSION: The detection rate of breast cancer was high, especially in the prevalence round. The trend in the incidence of breast cancer at the subsequent rounds was similar to that before screening, which indicates that mammography screening does not lead to any greater over-diagnosis. The rate of false positive mammography was high at the initial screening round, but was acceptable at subsequent rounds, and a false positive mammography does not seem to have affected participation in subsequent rounds. The Copenhagen screening programme conforms to international quality assurance guidelines for process evaluation.

[Mammographic screening in the municipality of Copenhagen 1991-1997. Evaluation of the preoperative assessment]. / Mammografiscreening i Københavns Kommune 1991-1997. Evaluering af det praeoperative udredningsforløb.

INTRODUCTION: A biennial mammography screening programme started for all women aged 50-69 in the municipality of Copenhagen, Denmark, in April 1991. The aim of the present study was to evaluate the quality of the preoperative diagnostic assessment for women recalled for further examination. Quality indicators were: validity of the fine-needle aspiration cytology, rate of malignant to benign surgery, and frequency of one-step surgery for malignant lesions. MATERIAL AND METHOD: Database registries during the first three screening rounds from April 1991 to March 1997 were studied retrospectively, for fine-needle aspiration cytology tests where surgical biopsy was also performed. RESULTS: In the period 1991-1997, 4,111 women were recalled for clinical mammography and subsequently 1,086 women underwent surgery. The use of the triple test in the preoperative assessment increased from 50% in the first screening round to 72% in the third. Throughout the period of evaluation, the number of inadequate fine-needle aspiration cytology (FNAC) was reduced from 32% to 6%. Inadequate FNAC from malignant lesions declined from 27% to 6%. The sensitivity of FNAC increased from 67% to 90% and the accuracy from 60% to 81%. The malignant/benign ratio of surgery rose from 1.4 in the first screening round to 2.8 in the third. One-step surgery as definitive treatment was performed in 67% of malignant instances. DISCUSSION: The preoperative diagnostic assessment improved during the evaluation period. The triple test was used more often over time, the validity of FNAC and the malignant/benign ratio of surgery increased.