Audit system on quality of breast cancer diagnosis and treatment (QT): results of quality indicators on screen-detected lesions in Italy in 2005 and preliminary results for 2006.

Within this survey, conducted by the Italian Group of Mammography Screening (GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2005, results showed overall good diagnosis and treatment quality, and an improving trend over time. Critical issues were identified in waiting times, compliance with the recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis has reached the acceptable target, but room for improvement still exists. The sentinel lymph node technique (SLN) was performed on the axilla in more than 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed to local and regional screening programmes in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume would provide the best setting for making audit effective in producing quality improvement.

Audit system on quality of breast cancer diagnosis and treatment (QT): results from the survey on screen-detected lesions in Italy, 2004.

Within this survey, conducted by the Italian Group for Mammography Screening (GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2004, overall results show a good diagnosis and treatment quality and an improving trend over time. Critical issues have been identified in waiting times, compliance to the recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis has reached an acceptable level, but room for improvement still exists. The sentinel lymph node technique (SLN) was performed on the axilla in almost 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed to local and regional screening programmes in order to enable multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volumes would provide the best setting for effective audits leading to quality improvement.

[Recommendations of a national Italian consensus conference on the opportunity of extending screening service by mammography to 40-49 and 70-74 years of age women]. / Raccomandazioni di una conferenza di consenso italiana sull'opportunità di estendere lo screening mammografico organizzato alle donne di 40-49 e 70-74 anni di età.

The Italian Mammography Screening Network (GISMa) held a national consensus conference in Bologna, May 25-26 2006. The large panel of participants included national experts in fields related to breast cancer and screening issues. The final aim was the production of a consensus statement which might become a standard reference for Italy. The consensus document (http://www.gisma.it) states that full national coverage by organized screening for breast (age 50-69), cervical and colorectal cancer is a priority, before any extension of organized mammography screening to younger or older age groups may be considered. If adequate resources are available, extension of organized screening for breast cancer until age 74 is recommended, at least for regular attenders until age 69. Extension of organized screening to women aged 40-49 may be considered at some conditions: (a) that resources are available, (b) that a 1-year interval is adopted, (c) that proper information of the limitations of screening is given to participants and (d) that priority is given to age 45-49.

Role of axillary ultrasound examination in the selection of breast cancer patients for sentinel node biopsy.

BACKGROUND: Sentinel node biopsy (SNB) is a time-consuming procedure that can be avoided in presence of axillary metastases. The aim of this study was to assess the accuracy of ultrasound scan (US) in the prediction of axillary nodes status in patients scheduled for SNB. METHODS: Axillary US was performed and when feasible, a core biopsy of suspicious nodes was taken. The nodal status as assessed by US and/or core biopsy was compared with final histology. RESULTS: Of the 132 patients enrolled, 31 (23.5%) had suspicious axillary nodes according to US; 19 (61.3%) were true positive, whereas 12 cases (38.7%) were not. In 14 of 31 suspicious cases an US-guided core-biopsy was taken, which in 11 of 14 cases (78.5%) confirmed the neoplastic involvement. Overall, core biopsy of the nodes correctly predicted the final histology in 13 of 14 cases (92.8%). CONCLUSIONS: The US of axillary nodes, possibly associated with core biopsy, improved the preoperative evaluation of breast cancer patients scheduled for SNB.

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results from the survey on screen-detected lesions in Italy, 2003-2004.

Within the Italian Breast Screening Network, individual data are collected yearly on about 50% of all screen-detected operated lesions. In 2003 results showed a good overall quality of diagnosis and treatment, and an improving trend over time. Critical issues were identified in the number of cancers diagnosed pre-operatively, which is still below standards, and in the waiting times for surgery. Compliance with recommendations as to not performing frozen section on small lesions and unnecessary axillary dissection for ductal carcinoma in situ still have not reached the target. The sentinel lymph node technique was performed on the axilla in more than 60% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. Preliminary data for 2004 show further progress towards better quality, particularly in pre-operative diagnosis and in the avoidance of frozen section. The detailed results of this survey have been distributed to local and regional screening programmes in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume would provide the best setting for making audit effective in producing quality improvement.

Breast cancer in the elderly: treatment of 1500 patients.

There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This study's goal was to evaluate disease-specific survival and local-regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1-87.3 years). The median follow-up was 8.7 years (range 1-30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan-Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease-specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease-free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors.

Isolation by size of epithelial tumor cells in peripheral blood of patients with breast cancer: correlation with real-time reverse transcriptase-polymerase chain reaction results and feasibility of molecular analysis by laser microdissection.

The aim of this study is the counting and the immunomorphological and molecular characterization of circulating tumor cells (CTCs) by the isolation by size of epithelial tumor cells (ISET) method in the peripheral blood of patients with breast cancer. An evaluation of the method's ability to reveal the presence of occult carcinoma cells in blood of a patient with breast cancer was performed and the results compared with those obtained by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for the evaluation of cytokeratin-19 (CK-19) mRNA expression. The feasibility of molecular analysis of CTCs after laser microdissection of filters used in ISET was illustrated, referring to HER-2 amplification. Blood samples drawn from 44 patients with breast cancer were preoperatively analyzed by ISET. From the same samples, total RNA was extracted and submitted to quantitative real-time RT-PCR for the detection of CK-19 mRNA-positive cells using TaqMan technology. HER-2 amplification was measured by real-time RT-PCR on DNA extracted from cells recovered by laser microdissection from 7 selected ISET-positive filters. Of 44 samples, 12 (27%) showed the presence of epithelial cells on the filter (mean +/- SE: 8.5 +/- 2.4 cells per milliliter of blood). A statistically significant agreement (P = .001) was observed between real-time RT-PCR results and those obtained by ISET. With regard to HER-2 amplification, a good correspondence was found between the results obtained from microdissected CTCs and those obtained using DNA extracted from the primary tumor (R = 0.918; P < .01), as well as the immunohistochemistry results. The ISET method allows for the collection of breast carcinoma cells by filtration despite their smaller dimension relative to other carcinoma cell types. The sensitivity and specificity of the method is comparable with those obtained using the quantitative real-time RT-PCR assay for the evaluation of CK-19 mRNA expression. Moreover, the laser microdissection technique allows for the recovery of nucleic acids for further molecular analysis and CTC characterization.

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial.

PURPOSE: Tamoxifen, which is actually the gold standard adjuvant treatment in estrogen receptor-positive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy because of the development of resistance. Therefore new approaches are required. PATIENTS AND METHODS: We conducted a prospective randomized trial to test the efficacy of switching postmenopausal patients who were already receiving tamoxifen to the aromatase inhibitor anastrozole. After 2 to 3 years of tamoxifen treatment, patients were randomly assigned either to receive anastrozole 1 mg/d or to continue receiving tamoxifen 20 mg/d, for a total duration of treatment of 5 years. Disease-free survival was the primary end point. Event-free survival, overall survival, and safety were secondary end points. RESULTS: Four hundred forty-eight patients were enrolled. All women had node-positive, estrogen receptor-positive tumors. At a median follow-up time of 36 months, 45 events had been reported in the tamoxifen group compared with 17 events in the anastrozole group (P = .0002). Disease-free and local recurrence-free survival were also significantly longer in the anastrozole group (hazard ratio [HR] = 0.35; 95% CI, 0.18 to 0.68; P = .001 and HR = 0.15; 95% CI, 0.03 to 0.65; P = .003, respectively). Overall, more adverse events were recorded in the anastrozole group compared with the tamoxifen group (203 v 150, respectively; P = .04). However, more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group (33 of 150 events v 28 of 203 events, P = .04). CONCLUSION: Switching to anastrozole after the first 2 to 3 years of treatment is well tolerated and significantly improves event-free and recurrence-free survival in postmenopausal patients with early breast cancer.

Role of axillary lymph node ultrasound and large core biopsy in the preoperative assessment of patients selected for sentinel node biopsy.

PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of axillary lymph node sonography, if necessary in combination with US-guided large core biopsy, in the preoperative evaluation of breast cancer patients scheduled for quadrantectomy and sentinel lymph node excision. MATERIALS AND METHODS: From July 2001 to December 2002, we evaluated 117 breast cancer patients with ultrasound and, where indicated, FNAB. Breast lesions had diameters between 4 and 26 mm (mean diameter 11 mm). Fifteen (13%) of the 117 patients were excluded from the series as they did not fulfil the criteria for preliminary sonography of the axilla: in 9 patients fewer than 4 nodes were detected and in 6 patients the breast lesions were intraoperatively found to be benign. Eleven patients (10.7 %) with sonographically suspicious axillary nodes were sampled by US-guided core biopsy using a 14 or 16 Gauge Tru-Cut needle. RESULTS: The ultrasound study aims to evaluate the dimensions and morphology of the breast lesion as well as detect and assess at least 4 axillary nodes. These were evaluated for hilar and cortical thickening and ratio between the sinus diameter and the total longitudinal diameter. Lymph nodes with hilar diameters equal to or greater than 50% of the longitudinal diameter were considered normal. Of the 102 patients evaluated, 77 (75.7%) had normal axillary nodes according to the US criteria adopted. Negativity was confirmed by histology in 56 cases (72.7%, true negative); 21 (27.3%, false negative) were found to be positive, in contrast with the sonographic appearance. The false negative cases were due to lymph node micrometastasis which probably did not cause morphologic alterations perceptible at ultrasound. The remaining 25 patients (24.5%) had axillary lymph nodes classified as suspicious. In 13 cases of (52%, true positive) there was agreement with histology, whereas in 12 cases (48%, false positive) the US suspicion was not confirmed at surgery. The most important sonographic alteration was the gradual reduction in hilar echogenicity (seen in 100% metastatic nodes); conversely, hilar denting or irregularities, as well as dimensional criteria, proved to be poorly specific. CONCLUSIONS: The sonographic assessment of axillary and internal mammary chain nodes, possibly in addition to core biopsy, improves the preoperative evaluation of breast cancer patients scheduled for conservative surgery of the breast (quadrantectomy) and the axilla (sentinel node biopsy). US findings suspicious for metastatic involvement of axillary lymph nodes should be considered as an exclusion criterion for sentinel node biopsy. A more widespread use of axillary node biopsy and an accurate sonographic evaluation of the excised lymph node increase the specificity of the procedure, allowing a better correlation between sonographic findings and definitive histology.

Tankyrase, a positive regulator of telomere elongation, is over expressed in human breast cancer.

Tankyrase promotes telomere elongation by interaction with the telomeric protein binding factor TRF1, a negative regulator of telomere extension. We measured tankyrase mRNA by real-time RT-PCR in 66 breast cancers and in paired normal tissues. Results were compared with hTERT mRNA expression. The levels of tankyrase in breast cancers were significantly higher in comparison to normal tissues (P<0.0001) and significantly related to the status of progesterone receptors. No relationship was found between tankyrase and hTERT mRNA expression in breast cancers. According to our results, tankyrase expression appeared up regulated in breast cancers.

Quantitative real-time reverse transcription polymerase chain reaction: normalization to rRNA or single housekeeping genes is inappropriate for human tissue biopsies.

Careful normalization is essential when using quantitative reverse transcription polymerase chain reaction assays to compare mRNA levels between biopsies from different individuals or cells undergoing different treatment. Generally this involves the use of internal controls, such as mRNA specified by a housekeeping gene, ribosomal RNA (rRNA), or accurately quantitated total RNA. The aim of this study was to compare these methods and determine which one can provide the most accurate and biologically relevant quantitative results. Our results show significant variation in the expression levels of 10 commonly used housekeeping genes and 18S rRNA, both between individuals and between biopsies taken from the same patient. Furthermore, in 23 breast cancers samples mRNA and protein levels of a regulated gene, vascular endothelial growth factor (VEGF), correlated only when normalized to total RNA, as did microvessel density. Finally, mRNA levels of VEGF and the most popular housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were significantly correlated in the colon. Our results suggest that the use of internal standards comprising single housekeeping genes or rRNA is inappropriate for studies involving tissue biopsies.