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M Bilous

Publications and source records attributed to M Bilous.

At least 19 recordsLinked to original sources

A risk index for early node-negative breast cancer.

BACKGROUND: This study compared the application of the St Gallen 2001 classification with a risk index developed at the New South Wales Breast Cancer Institute (BCI Index) for women with node-negative breast cancer treated without adjuvant systemic therapy. METHODS: The BCI risk categories were constructed by identifying combinations of prognostic indicators that produced homogeneous low-, intermediate- and high-risk groups using the same variables as in the St Gallen classification. RESULTS: The BCI low-risk category consisted of women aged 35 years or more with a grade 1 oestrogen receptor (ER)-positive tumour 20 mm or less in diameter, or with a grade 2 ER-positive tumour of 15 mm or less. This category constituted 40.1 per cent of patients, with a 10-year distant relapse-free survival (DRFS) rate of 97.2 per cent. The BCI intermediate-risk category included women aged 35 years or more with a grade 2 ER-positive tumour of diameter 16-20 mm, or a grade 1 or 2 ER-negative tumour measuring 15 mm or less, and comprised 12.1 per cent of the women, with a 10-year DRFS rate of 88 per cent. The high-risk category comprised 47.7 per cent of women, with a 10-year DRFS rate of 68.4 per cent. CONCLUSION: If confirmed in other data sets, the BCI Index may be used to identify women at low risk of distant relapse (2.8 per cent at 10 years) who are unlikely to benefit from adjuvant systemic therapy, and women at intermediate risk of distant relapse (12 per cent at 10 years) in whom the benefit of adjuvant systemic therapy is small.

Adult↗

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study.

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC ) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC.

Adult↗

Mapping of quantitative trait loci for field resistance to Fusarium head blight in an European winter wheat.

Fusarium head blight (FHB) caused by Fusarium culmorum is an economically important disease of wheat that may cause serious yield and quality losses under favorable climate conditions. The development of disease-resistant cultivars is the most effective control strategy. Worldwide, there is heavy reliance on the resistance pool originating from Asian wheats, but excellent field resistance has also been observed among European winter wheats. The objective of this study was to map and characterize quantitative traits loci (QTL) of resistance to FHB among European winter wheats. A population of 194 recombinant inbred lines (RILs) was genotyped from a cross between two winter wheats Renan (resistant)/Récital (susceptible) with microsatellites, AFLP and RFLP markers. RILs were assessed under field conditions For 3 years in one location. Nine QTLs were detected, and together they explained 30-45% of the variance, depending on the year. Three of the QTLs were stable over the 3 years. One stable QTL, QFhs.inra.2b, was mapped to chromosome 2B and two QTLs QFhs.inra.5a2 and QFhs.inra5a3, to chromosome 5A; each of these QTLs explained 6.9-18.6% of the variance. Other QTLs were identified on chromosome 2A, 3A, 3B, 5D, and 6D, but these had a smaller effect on FHB resistance. One of the two QTLs on chromosome 5A was linked to gene B1 controlling the presence of awns. Overlapping QTLs for FHB resistance were those for plant height or/and flowering time. Our results confirm that wheat chromosomes 2A, 3A, 3B, and 5A carry FHB resistance genes, and new resistance factors were identified on chromosome arms 2BS and 5AL. Markers flanking these QTLs should be useful tools for combining the resistance to FHB of Asian and European wheats to increase the resistance level of cultivars.

Biometry↗

Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy.

BACKGROUND: The 1998 St Gallen classification was devised to guide clinicians in the use of adjuvant systemic therapy for women with early breast cancer. In this study, the classification was applied to a historical group of patients with node-negative breast cancer who were treated without adjuvant therapy. METHODS: The St Gallen classification was applied to 421 women with breast cancer treated with conservative surgery and radiotherapy alone between 1979 and 1994. Primary tumour characteristics were reviewed centrally. RESULTS: When the most stringent version of the St Gallen classification was applied (grade 2 or 3 tumours classified as "high risk"), only 10 per cent of patients were "low risk", with a 10-year distant relapse-free survival (DRFS) rate of 100 per cent, and 15 per cent were at "intermediate risk" (10-year DRFS rate of 94 per cent). The high-risk group (75 per cent of women) had a 10-year DRFS rate of 77 per cent (P < 0.01). If the St Gallen classification had been applied to all patients in this series who were aged less than 70 years, up to 91 per cent would have been recommended to have chemotherapy. CONCLUSION: The St Gallen classification is an inaccurate measure of prognosis for patients with node-negative breast cancer and should be used with caution.

Adult↗

Treatment implications of a positive sentinel lymph node biopsy for patients with early-stage breast carcinoma.

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy is emerging as an alternative to axillary lymph node dissection (ALND) in determining the lymph node status of patients with early-stage breast carcinoma. The hypothesis of the technique is that the SLN is the first lymph node in the regional lymphatic basin that drains the primary tumor. Non-SLN (NSLN) metastasis in the axilla is unlikely if the axillary SLN shows no tumor involvement, and, thus, further axillary interference may be avoided. However, the optimal treatment of the axilla in which an SLN metastasis is found requires ongoing evaluation. The objectives of this study were to evaluate the predictors for NSLN metastasis in the presence of a tumor-involved axillary SLN and to examine the treatment implications for patients with early-stage breast carcinoma. METHODS: Between June 1998 and May 2000, 167 patients participated in the pilot study of SLN mapping and biopsy at Westmead Hospital. SLNs were identified successfully and biopsied in 140 axillae. All study patients also underwent ALND. The incidence of NSLN metastasis in the 51 patients with a SLN metastasis was correlated with clinical and pathologic characteristics. RESULTS: Of 51 patients with a positive SLN, 24 patients (47%) had NSLN metastases. The primary tumor size was the only significant predictor for NSLN involvement. NSLN metastasis occurred in 25% of patients (95% confidence interval [95%CI], 10-47%) with a primary tumor size </= 20 mm and in 67% of patients (95%CI, 46-83%) with a primary tumor size > 20 mm (P = 0.005). The size of the SLN metastasis was not associated significantly with NSLN involvement. Three of 7 patients (43%) with an SLN micrometastasis (< 1 mm) had NSLN involvement compared with 38 of 44 patients (48%) with an SLN macrometastasis (> or = 1 mm). CONCLUSIONS: The current study did not identify a subgroup of SLN positive patients in whom the incidence of NSLN involvement was low enough to warrant no further axillary interference. At present, a full axillary dissection should be performed in patients with a positive SLN.

Adult↗

Complex sclerosing lesion: the lesion is complex, the management is straightforward.

BACKGROUND: Complex sclerosing lesion (CSL) and its smaller counterpart, the radial scar (RS), are frequently seen pathological entities. They are clinically asymptomatic and, prior to the implementation of mammographic screening, were most commonly found incidentally during pathological examination of other biopsied lesions. Complex sclerosing lesions are being detected regularly on mammograms due to widespread screening; many of their features resemble those of malignancy. Management varies and has been controversial. METHODS: Twenty-three cases of CSL detected during the first prevalent round of screening at BreastScreen Western Sydney (from February 1993 until June 1995) are presented and reviewed. Assessment was by a combination of radiological, clinical and cytological work-up prior to surgical biopsy. In addition, 126 spiculated carcinomas detected in the same period were reviewed and compared. RESULTS: Fourteen RS/CSL (62%) had lucent centres and nine (38%) had a central mass; three had been diagnosed provisionally as RS/CSL. Spicule lengths ranged from 25 to 90 mm; central masses ranged from 5 to 50 mm; and mass:spicule length ratio ranged from 1.2:1 to 1:10. Calcification (benign or indeterminate) was present in six cases (29%). No RS/CSL contained 'suspicious' calcifications, whereas 120 of 126 carcinomas (95%) had a central mass and six (5%) had a lucent centre (spicule lengths: 10-90 mm; central mass: 5-40 mm; and mass:spicule length ratio: 1.1:1-1:10). Twenty-one spiculated carcinomas (17%) contained microcalcifications (14 benign or indeterminate; seven suspicious). Provisional radiological diagnosis (PRD) after mammogram, with or without ultrasound, for histologically confirmed RS/CSL, was RS/CSL in 18 cases (78%), carcinoma in four cases (17%) and equivocal in one case (5%). For eight (6.5%) spiculate carcinomas the PRD was RS/CSL prior to histological diagnosis. The RS/CSL were detected with equal frequency in right and left breasts, and 22 (96%) lesions occurred in the upper breast. Seven RS/CSL (31%) and 83 spiculated carcinomas (65%) had been described as 'palpable' but most were subtle. Twelve fine-needle aspiration biopsies were performed (six 'palpable' lesions (no radiological guidance); four with ultrasound guidance and two with stereotactic guidance), and five (62.5%) of eight adequate lesions were reported as benign, two (25%) were reported as atypical, and one (12.5%) was reported as suspicious. CONCLUSIONS: Definitive mammographic and sonographic differentiation of RS/CSL and stellate-type carcinoma is impossible. For screen-detected lesions that may be RS/CSL, the appropriate surgical procedure is a small but adequate biopsy using guidewire or other localization methods with optimal cosmetic incision.

Biopsy, Needle↗

HER2 testing recommendations in Australia.

HER2 is the target of a new treatment for metastatic breast cancer using the humanised monoclonal antibody trastuzumab (Herceptin). Since only around 20% of breast cancers carry the overexpressed HER2 receptor protein to which this treatment is directed, patient selection is very important in determining eligibility for the drug. Currently, immunohistochemistry and fluorescence in situ hybridisation are the main tests used for HER2 detection, and these testing recommendations have been developed based on national and international data.

Algorithms↗

Recent developments in stereotactic breast biopsy methodologies: an update for the surgical pathologist.

Recently, there have been a number of new devices introduced for stereotactic biopsy of nonpalpable, mammographically detected lesions. The vacuum-assisted core biopsy (VACB) (Minimal Invasive Breast Biopsy (MIBB), U.S. Surgical, Norwalk, CT; Mammotome, Biopsys Medical, Cincinnati, OH) obtains multiple tissue cores (11-gauge) in a circumferential manner around the biopsy probe, inserted under stereotactic guidance. It provides more complete sampling of mammographic lesions than the conventional 14-gauge stereotactic core biopsy, reducing the number of unsatisfactory biopsies. The advanced breast biopsy instrumentation (ABBI) (United States Surgical Corporation, Norwalk, CT) system utilizes stereotactic technique and an oscillating blade-cutting mechanism to obtain a single large diameter (5 mm to 20 mm) tissue core, with the aim of obtaining an intact lesion in its entirety for histologic assessment. Its potential as a treatment option is still under investigation. Suggested protocols for specimen handling are presented together with a review of the recent literature. Close liaison with radiologists and surgeons performing these biopsies will allow the collection of further outcome data to evaluate the strengths and weaknesses of each technique.

Biopsy, Needle↗

An audit of breast cancer pathology reporting in Australia in 1995.

To measure the quality of pathology reporting of breast cancer and establish a baseline against which future changes can be measured, we audited item completeness in breast cancer reports in Australia in 1995 before the release of specific recommendations from the Australian Cancer Network. Tumour type and size were given in reports of invasive breast cancer for 93% of women, 70% had, in addition, grade and clearance of the margins while only 28% had all recommended information. The most complete items in reports were histological type of breast cancer (99.6% of cases), tumour size (94%, 95% confidence interval (CI) 92-95) and margins of excision (87%, 95% CI 85-89). Histological grade (84%, 95% CI 82-86 of cases) and presence or absence of ductal carcinoma in situ (DCIS) (79%, 95% CI 77-81) were less complete and vessel invasion (61%, 95% CI 58-63) and changes in non-neoplastic breast tissue adjacent to the breast cancer (68%, 95% CI 66-71) the least complete. Less than half the reports of DCIS reported on tumour size (49%, 95% CI 42-57), presence or absence of necrosis (41%, 95% CI 34-49) or nuclear grade (39%, 95% CI 31-46). Around 1500 reports were identified as issued by 147 laboratories and 392 pathologists; 69% of pathologists issued fewer than two reports a month in the audit. We concluded that infrequency of reporting may have contributed to incompleteness of reporting. In addition, we found significant variation across Australian states with some indication that reporting was consistently poor in one state. The audit highlighted areas for improvement for breast cancer reporting in Australia. Research evidence suggests that multifaceted strategies are needed to assist practitioners with implementing more uniform reporting standards.

Aged↗

Conservative surgery and radiation therapy for invasive lobular carcinoma of the breast.

BACKGROUND: There is debate as to whether infiltrating lobular carcinoma (ILC) can be effectively treated with breast conservative surgery (CS) and radiotherapy (RT) because of a perceived high risk of local recurrence. This retrospective study examined the outcome of patients with ILC treated by CS and RT. METHODS: Between November 1979 and December 1994, 57 women with UICC Stage I or II ILC were treated by CS and RT at Westmead Hospital, New South Wales, Australia. The median age was 55 years (range 28-79). Twelve patients (21%) underwent a re-excision after initial CS. The final margins were clear for 43 patients (75.4%), positive (invasive or in situ) for nine patients (15.8%), and indeterminate for five patients (8.8%). All patients received whole-breast irradiation (45-50.4 Gy) usually supplemented by a boost (10-30 Gy). Fifty-three of 57 patients (93%) had their pathology reviewed at Westmead Hospital. RESULTS: After a median follow up of 69 months (range 36-162) three patients (5.3%) developed a local recurrence. One of 43 patients (2.3%) with known clear margins developed a local recurrence compared with two of 14 patients (14.3%) with positive or indeterminate margins (P = NS). The 5- and 10-year rates of freedom from local recurrence were 96 and 93%, respectively. The 5-year disease-free survival was 85% (node-negative, 92%; node-positive, 66%). Overall survival was 94% at 5 years. No patient developed a contralateral breast cancer. CONCLUSION: Patients with ILC can be effectively treated with CS and RT.

Actuarial Analysis↗

Is centralized histopathology review necessary for screen-detected breast lesions?

To address quality requirements for breast pathology in the Australian screening programme, one breast cancer Screening and Assessment Service initiated a process of central pathologic review of all lesions detected through the service. The aim of this study was to measure concordance between the initial and review pathology, and to assess the merit of routine review. Concordance was measured by observed agreement and the kappa statistic for 267 women with 273 lesions. Concordance was excellent for the four classification schemes examined, good for the identification of benign lesions and hyperplasia, and excellent for the identification of DCIS or invasive carcinoma. For the sub-categorization of hyperplasias and invasive carcinomas concordance was good, but was poor for the sub-typing of DCIS. Initial and review concordance was acceptable, suggesting that disagreement among pathologists may not present a major impediment to the provision of dependable diagnoses. Full case review is unnecessary for benign lesions or invasive carcinoma, but should be maintained for DCIS and hyperplasias.

Journal Article↗

Carcinomas of the renal pelvis associated with smoking and phenacetin abuse: p53 mutations and polymorphism of carcinogen-metabolising enzymes.

Phenacetin abuse and smoking are established risk factors for transitional cell carcinomas of the urinary tract. In the present study, we analysed exposure and the clinical course of patients who underwent nephrectomy for transitional cell carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded histological sections followed by direct DNA sequencing revealed that 29 of 89 (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were found in 4 tumours and triple mutations in 1 tumour. The incidence of p53 mutations was significantly higher in tumours with grades 3 and 4 than in those with grades 1 and 2 and higher in invasive than in non-invasive tumours. Furthermore, patients with carcinomas carrying a p53 mutation showed poorer survival than those without mutation. The type of p53 mutation in renal pelvic carcinomas was similar to that reported for bladder cancer, G:C-->A:T transition mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C-->T:A and G:C-->C:G transversions. The incidence and type of p53 mutation did not differ significantly in patients with a history of phenacetin abuse, smoking or neither of these habits. This was also true for G:C-->T:A transversions (17.5% of mutations), which are considered typical of smoking-induced carcinomas at other sites, e.g., lung, oral cavity and oesophagus. Our results indicate that the frequency and pattern of p53 mutations are similar in transitional cell carcinomas of the bladder and the renal pelvis and do not reflect exposure to phenacetin and/or smoking. The frequency of genetic polymorphism in genes coding for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1 and GSTM1) was also independent of exposure. Although the sample size of our study does not allow definite conclusions, these data are compatible with chronic tissue damage as a causative factor in the evolution of urothelial carcinomas rather than pointing to a direct mutagenic effect of phenacetin and tobacco-specific carcinogens.

Aged↗

Ductal carcinoma in situ. Part 2: Treatment.

Several dilemmas exist when treating a patient with ductal carcinoma in situ (DCIS): the high rate of inter-observer variation for pathologists who must diagnose these tumours; the potential for over- and under-treatment; and the uncertainty about the best way to inform a patient who must often make a decision between breast conservation and mastectomy. Mastectomy is nearly 100% curative, is expedient, but may represent over-treatment for many women, particularly those with asymptomatic mammographically detected lesions. Axillary dissection is not recommended as a routine except for patients with lesions over 5 cm in whom the risk of micro-invasion and lymph node involvement increases. Conservative surgery (CS) alone is associated with a local recurrence rate of approximately 20%, and half of these recurrences (10% overall) are invasive, with a potential long-term cure rate of at least 90%. The addition of radiation to CS reduces the risk of local recurrence to approximately 10%, half of these recurrences (5%) are invasive for a potential long-term cure rate of 95%. Several randomized trials comparing CS with or without radiation therapy (RT) are in progress. The factors that increase the rate of local recurrence after CS alone for DCIS include close or involved margins, and the presence of necrosis or high-grade tumours. Patients with these features should have radiation therapy if breast conservation is preferred. Patients with low-grade tumours (without necrosis) up to 15 mm, with clear margins of at least 10 mm, who agree to be closely observed may be good candidates for CS alone. A critical review of the literature is presented.

Breast Neoplasms↗

Fine-needle biopsy specimens of benign breast lesions distinguished from invasive cancer ex vivo with proton MR spectroscopy.

PURPOSE: To determine whether invasive breast cancer can be distinguished from benign lesions with proton magnetic resonance (MR) spectroscopy ex vivo on the basis of altered cellular chemistry. MATERIALS AND METHODS: Two hundred eighteen fine-needle biopsy specimens were obtained in 191 patients undergoing surgery and were analyzed with proton MR spectroscopy. MR spectroscopic and histopathologic findings were compared. RESULTS: Invasive carcinoma produced increased signal at 3.25 ppm, attributable to choline-containing metabolites. Discrimination between invasive carcinoma (n = 82), benign lesions (n = 106), or carcinoma in situ (n = 17) was based on the resonance intensity at 3.25 ppm standardized to the resonance at 3.05 ppm (P < .001). The ratio of peak height intensities of resonances at 3.25 to those at 3.05 ppm was less than 1.7 in 102 of the 106 normal or benign lesions. All carcinoma in situ specimens with comedonecrosis or a microinvasive component (n = 6) were categorized at MR spectroscopy with invasive carcinoma, while others with in situ disease alone were categorized with benign lesions (n = 11). The sensitivity and specificity of MR spectroscopy in fine-needle biopsy specimens in distinguishing benign lesions from invasive cancer were 95% and 96%, respectively. CONCLUSION: Proton MR spectroscopy of fine-needle biopsy specimens provides objective diagnostic information that complements findings of conventional preoperative investigations of breast lesions.

Adult↗

Prognostic significance of c-erbB-2 oncogene in axillary node-negative breast cancer.

BACKGROUND: With the advent of screening mammography more breast cancer will be detected at an earlier stage, apparently confined to the breast with no nodal involvement. However, 30% of these will recur due to micrometastases present at the time of diagnosis. Chemotherapy and tamoxifen have been shown to improve disease-free survival in axillary node-negative patients but not overall survival. In the search for a useful predictor of breast cancer recurrence the relationship between c-erbB-2 expression and recurrence and survival was examined. METHODS: Eighty-eight axillary node-negative breast cancer patients were followed up for at least 5 years. RESULTS: There was a significant relationship between c-erbB-2 expression and both tumour recurrence (P<0.001) and poorer survival (P=0.003). In a Cox multiple regression analysis, c-erbB-2 staining remained the only significant prognostic variable for recurrence (P=0.002) and survival (P=0.032). Tumour recurrence in c-erbB-2-positive cases tended to occur early in the course of follow up and was associated with poorer survival. CONCLUSION: C-erbB-2 was found to be a useful prognostic indicator for early recurrence and poorer survival in axillary node-negative breast cancer patients.

Adult↗

Breast cancer: getting the diagnosis right.

Distinguishing between early breast cancer and benign conditions, which are much more common, can be difficult. Careful clinical examination and directed imaging, supported by fine needle aspiration cytology, provide a high level of diagnostic accuracy.

Biopsy, Needle↗

Sarcomas following radiation therapy for breast cancer: a report of three cases and a review of the literature.

PURPOSE: First to describe clinical and pathologic features of sarcomas arising after radiation therapy for breast cancer and to report three cases of sarcoma arising 7, 15, and 20 years following radiation therapy for breast cancer. Second, to review the literature on this treatment complication. METHODS AND MATERIALS: Medline literature search. RESULTS: The most frequent histology is osteosarcoma and bone is affected more commonly than soft tissue at a median latency of 11 years. The scapula is the most frequently affected bone. The most frequently affected soft tissue site is now the conserved breast with a median latency of 5.5 years. The aetiologic factors relating to these sarcomas are not fully defined with factors of beam energy, radiation dose, chemotherapy and regional edema being inconsistently reported. CONCLUSION: The frequency of radiation-induced sarcoma at 10 years of follow-up is approximately 0.2%. This is an overestimate by an unknown factor because of the description of sarcomas arising metachromously in breast cancer patients, in nonirradiated areas.

Adult↗