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Biomedical subjects

Thomas B Julian

Publications and source records attributed to Thomas B Julian.

13 recordsLinked to original sources

Detection of occult sentinel lymph node micrometastases by immunohistochemistry in breast cancer. An NSABP protocol B-32 quality assurance study.

BACKGROUND: Occult metastases, by definition, are not detected on initial examination. They may be present on slides but missed during screening or may be present in paraffin embedded tissue blocks and undetected without additional levels. Anticytokeratin immunohistochemistry (CK IHC) enhances detection of occult metastases, particularly micrometastases (> 0.2 mm but not larger than 2.0 mm) or isolated tumor cell clusters (< or = 0.2 mm). This study defines the rate at which pathologists miss metastases on CK IHC of sentinel lymph nodes (SLN). METHODS: CK IHC sections 0.5 and 1.0 mm from the original surface of SLN tissue blocks were screened by pathologists using standard bright field light microscopes (LM) and by supervised computer assisted cell detection (CACD). All blocks were from breast cancer patients, initially classified 'node negative' on review of routinely stained sections from the surface of each block. Cases missed by LM screening but detected by CACD defined false negative screens. RESULTS: Of 236 cases screened, LM detected 34 (14.4%; 95% CI: 9.6-20.2) cases and, in the 202 cases negative by LM, CACD detected an additional 30 (14.9%; 95% CI: 9.6-21.2%) cases with occult metastases. Occult metastases missed by LM screening ranged from 0.01 to 0.1 mm in greatest dimension. The probability of missing an occult metastasis < or = 0.02 mm; < or = 0.05 mm, and < or = 0.10 mm was 75%, 69.2%, and 61.2%, respectively. No occult metastases larger than 0.10 mm were missed by LM screening. CONCLUSIONS: Pathologists screening the CK IHC stained slides may frequently miss detecting metastases < 0.10 mm.

Axilla↗

Added cancer yield of MRI in screening the contralateral breast of women recently diagnosed with breast cancer: results from the International Breast Magnetic Resonance Consortium (IBMC) trial.

OBJECTIVE: To estimate the added cancer yield of magnetic resonance imaging (MRI) over mammography in the contralateral breast of patients with a recent diagnosis of breast cancer. METHODS: We conducted a prospective, international study of mammography and MRI in women with a recent diagnosis of unilateral breast cancer. Each subject received a mammogram, clinical breast exam (CBE), and MRI of the unaffected breast within a 90 day time period. Definitive diagnosis of suspicious findings was determined through biopsy and central pathology review. RESULTS: Of the 103 eligible women included in study analyses, MRI detected 4 cancers in the contralateral breast while mammography detected none. MRI resulted in 12% (95% CI, 6%-20%) of women recommended for biopsy and 10% of women undergoing additional biopsy. The added cancer yield of MRI was 4% (95% CI, 1%-10%) and the positive predictive value of an abnormal MRI was 33% (95% CI, 10%-65%). Forty percent (4/10) of the biopsies performed based on the MRI recommendation were positive for malignancy. CONCLUSION: In women with a recent breast cancer diagnosis, approximately 4% will have an otherwise occult invasive breast cancer detected in the opposite breast by MRI alone.

Biopsy↗

Prerandomization Surgical Training for the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial: a randomized phase III clinical trial to compare sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer.

OBJECTIVE: To train surgeons in a standardized technique of sentinel lymph node biopsy and to prepare them for the requirements of a prospective randomized surgical trial. SUMMARY BACKGROUND DATA: The NSABP B32 trial opened to accrual in May 1999. A significant component of this trial was a prerandomization training phase of surgeons performed by a group of core surgical trainers. The goals of this training phase were to expeditiously instruct surgeons in a standardized technique of sentinel lymph node biopsy and to educate those same surgeons in complete and accurate data collection and source documentation for the trial. METHODS: This study is a description of the training data collected in a prospective fashion for the training component for surgeon entry into the B32 trial, evaluating the effectiveness of the training program in regards to surgical outcomes and protocol compliance. RESULTS: Two hundred twenty-six registered surgeons underwent site visit training by a core surgical trainer and 187 completed training and were approved to randomize patients on the trial. The results of 815 training (nontrial) cases demonstrated a technical success rate for identifying sentinel nodes at 96.2% with a false negative rate of 6.7%. A protocol compliance analysis, which included the evaluation of 94 separate fields, showed mean protocol compliance of 98.6% for procedural fields, 95.5% for source documentation fields and 95.0% for data entry fields. CONCLUSIONS: This training and quality control program has resulted in a large number of surgeons capable of performing sentinel lymph node biopsy in a standardized fashion with a high degree of protocol compliance and pathologic accuracy. This will ensure optimal results for procedures performed on the randomized phase of the trial.

Axilla↗

Mammographic density and breast cancer after ductal carcinoma in situ.

Women with ductal carcinoma in situ (DCIS) are at substantially increased risk for a second breast cancer, but few strong predictors for these subsequent tumors have been identified. We used Cox regression modeling to examine the association between mammographic density at diagnosis of DCIS of 504 women from the National Surgical Adjuvant Breast and Bowel Project B-17 trial and risk of subsequent breast cancer events. In this group of patients, mostly 50 years old or older, approximately 6.6% had breasts categorized as highly dense (i.e., > or =75% of the breast occupied by dense tissue). After adjusting for treatment with radiotherapy, age, and body mass index, women with highly dense breasts had 2.8 (95% confidence interval [CI] = 1.3 to 6.1) times the risk of subsequent breast cancer (DCIS or invasive), 3.2 (95% CI = 1.2 to 8.5) times the risk of invasive breast cancer, and 3.0 (95% CI = 1.2 to 7.5) times the risk of any ipsilateral breast cancer, compared with women with less than 25% of the breast occupied by dense tissue. Our results provide initial evidence that the risk of second breast cancers may be increased among DCIS patients with highly dense breasts.

Adult↗

NSABP-32: Phase III, randomized trial comparing axillary resection with sentinal lymph node dissection: a description of the trial.

The NSABP-32 trial is a randomized, phase III clinical trial to compare sentinel node (SN) resection to conventional axillary dissection in clinically node-negative breast cancer patients. The primary aims of the trial are to determine if removal of only SNs provides survival and regional control equivalent to those of axillary dissection, while diminishing the magnitude of surgically related side effects. In order to ensure consistency of the outcomes for this trial, a standardized method of SN surgery has been utilized for all cases. A secondary aim of the B32 trial is to evaluate whether patients with "occult" metastases in the SNs have worse survival. Accrual is taking place at 73 institutions in North America, and 217 surgeons are enrolling patients.

Axilla↗

Accelerated partial breast irradiation after conservative surgery for breast cancer.

OBJECTIVE: To critically review the theoretical and actual risks and benefits of accelerated partial breast irradiation (APBI) after breast-conserving surgery. SUMMARY BACKGROUND DATA: Because of rapid evolution of radiation therapy techniques related to brachytherapy and three-dimensional conformal radiation therapy, APBI has very recently come to the forefront as a potential local treatment option for women with breast cancer. This review aims to give an overview of the biologic rationale for APBI techniques, and benefits and limitations of APBI techniques. METHODS: The authors reviewed the currently available published world medical literature on breast-conserving surgery with and without postoperative irradiation; all studies involving partial breast irradiation, including brachytherapy, for breast cancer; and currently accruing and planned APBI trials. The focus of this review was the early results of treatment in terms of toxicity, complications, cosmesis, and local control. RESULTS: On average, approximately 3% of patients treated with breast-conserving surgery will have an in-breast local recurrence away from the original lumpectomy site with or without postoperative standard whole-breast irradiation. The results of phase I-II studies involving approximately 500 patients treated with APBI after breast-conserving surgery have been published. Although many of the studies have limited long-term follow-up and potential selection bias, early results suggest that toxicity, cosmesis, and local control are comparable to outcomes seen after breast-conserving surgery followed by standard whole-breast irradiation. CONCLUSIONS: Recent advances in radiation delivery and published series of partial breast irradiation support large randomized trials comparing APBI with standard whole-breast irradiation after breast-conserving surgery.

Brachytherapy↗

Technical limitations of sentinel node biopsy in breast cancer: a single surgeon's experience.

Few studies have attempted to critically identify patient- and tumor-related factors that limit sentinel node biopsy (SNB). These studies have been limited by sample size and surgeon variability. The present study attempts to enumerate these limitations in a unique group of patients. One hundred twenty-five SNBs performed by a single surgeon between May 1997 and June 2001 were reviewed. Overall SNB was successful in 96 per cent of patients with a 97 per cent correlation with the axillary node dissection. Sentinel node identification was not affected by age, tumor size, tumor location, prior segmental resection, or neoadjuvant therapy. No false negatives were noted in the neoadjuvant group. The use of blue dye alone significantly understaged patients when compared with isotope alone (P = 0.02). SNB is a highly accurate method to identify axillary metastases and its limitations are not affected by patient or tumor related factors. In the present study SNB detection by both isotope and blue dye has been shown to be superior to blue dye alone. This finding demonstrates that these limitations may be overcome with the standardization of the technique used.

Age Factors↗

Sentinel node biopsy after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: After neoadjuvant chemotherapy, while results of sentinel node biopsy (SNB) are encouraging, conditions that may affect sentinel node (SN) detection and false negative rates with respect to clinical and pathological tumor response after neoadjuvant therapy require investigation. METHODS: Thirty-four patients with clinical stage I, II and IIIA invasive breast cancer underwent neoadjuvant chemotherapy with doxorubicin/cyclophosphamide or doxorubicin/cyclophosphamide and docetaxel/segmental resection, SNB, and axillary node dissection (AND). RESULTS: SNs were found in 31 of 34 patients (91.2%). SNs were found in 20 of 21 patients (95.2%) with complete clinical tumor response, it was positive in 40% and no false negatives occurred. SNs were found in 11 of 13 patients (84.6%) with partial or no clinical tumor response; in four patients (33%) the SN was positive and no false negative nodes were found. Seven patients had complete pathological tumor response. SNs were found in six of these patients (85.7%). The SN was positive in 1 of 6 patients (16.7%) with no false negative. In 25 of 27 patients (92%) with partial or no pathological tumor response, the SN was identified. Eleven of these patients (44%) had positive nodes with no false negatives. CONCLUSIONS: SN identification rate and accuracy after neoadjuvant chemotherapy for breast carcinoma were extremely good however there is potential for inaccuracy after less than complete pathological tumor response. Further evaluation of SNB in larger clinical trial is warranted prior to accepting this approach as a standard care.

Antineoplastic Combined Chemotherapy Protocols↗