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P I Borgen

Publications and source records attributed to P I Borgen.

At least 19 recordsLinked to original sources
PubMed2007

The role of sentinel lymph node biopsy in Paget's disease of the breast.

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard of care for axillary lymph node staging in breast cancer and appears suitable for virtually all patients with clinically node-negative (cN0) invasive disease. However, its role in Paget's disease of the breast, a condition in which invasion may or may not be present, remains undefined. METHODS: Among 7,083 consecutive SLN biopsy procedures, we retrospectively identified 39 patients with Paget's disease of the breast. Nineteen patients had no associated clinical/radiographic features ("Paget's only"), and 20 patients had associated clinical/radiographic findings ("Paget's with findings"). RESULTS: The mean ages for the Paget's alone and with findings groups were 63.6 and 49.6 years, respectively. The use of breast conservation therapy was 32% in the Paget's alone group and 10% in the Paget's with findings group. Invasive carcinoma was found in 27% of patients in the Paget's alone group and 55% of patients in the Paget's with findings group. The success rate of SLN biopsy was 98%, and the mean number of SLNs removed was 3 in both groups. In the entire cohort of Paget's disease, 28% (11/39) of the patients had positive SLNs (11%, Paget's alone; 45%, Paget's with findings). CONCLUSION: In our "Paget's only" cohort, invasive cancer was found in 27% of cases and positive SLNs in 11%. SLN biopsy should be considered in all patients with Paget's disease of the breast, whether associated clinical/radiographic findings are present.

Adult↗
PubMed2003

Magnetic resonance imaging detects unsuspected disease in patients with invasive lobular cancer.

BACKGROUND: Predicting the extent of disease in the breasts of patients with invasive lobular cancer (ILC) can be difficult because of the limits of physical examination and standard imaging. We determined the utility of magnetic resonance imaging (MRI) in finding otherwise unsuspected cancer in the ipsilateral or contralateral breast of patients with ILC. METHODS: Through database review of all breast MRIs performed between January 1, 1999, and December 30, 2002, we identified patients with newly diagnosed ILC who underwent an MRI for extent-of-disease evaluation or contralateral screening. MRI findings separate from the primary tumor were biopsied and correlated with pathology by using MRI-guided biopsy. RESULTS: Sixty-two patients were identified. In all, 59 ipsilateral and 57 contralateral studies were performed. Suspicious lesions separate from the primary tumor were found by MRI in 38 (61%) of 62 patients. Eight patients were excluded from further analysis (seven elected mastectomy without biopsy; one had an unguided excision). Nineteen of 51 patients with an ipsilateral finding underwent MRI-guided biopsy, which revealed cancer in 11, or 22% of those imaged. Twenty of 53 patients with a contralateral finding underwent MRI-guided biopsy, which revealed cancer in 5, or 9% of those imaged. CONCLUSIONS: MRI of the breast identifies unsuspected multicentric or contralateral cancer in patients with ILC. These findings support the use of MRI in selected patients with ILC, particularly in the ipsilateral breast.

Biopsy↗
PubMed2002

A prospective validated model for predicting axillary node metastases based on 2,000 sentinel node procedures: the role of tumour location [corrected].

AIMS: The purpose was to identify the independent predictive factors of axillary lymph-node metastases (ALNM) in infiltrating ductal carcinoma (IFDC) and to create a prospective, validated statistical model to predict the likelihood of ALNM in patients in the present era of sentinel lymph-node (SLN) biopsy and enhanced histopathology. METHODS: Univariate and multivariate analyses of 13 clinicopathological variables (including tumour location) were performed to determine predictors of ALNM in 1659 eligible SLN biopsy procedures. A logistic regression model was developed and then prospectively validated on a second population of 187 subsequent consecutive procedures. RESULTS: Age, pathological tumour size, palpability, lymphovascular invasion (LVI), histological grade, nuclear grade, ductal histological subtype, tumour location (quadrant) and multifocality were associated with ALNM in univariate analyses (P < 0.001). Of these, only palpability and histological grade were not statistically associated with ALNM in the multivariate analysis (P> 0.05). The frequency of ALNM in upper-inner-quadrant (UIQ) tumours was 20.6%, compared with 33.2% for all other quadrants (P<0.0005). There was no statistical difference between UIQ and other-quadrant tumours in any clinicopathological variables analysed. The logistic regression model, developed based on the population of 1659, had the same accuracy, sensitivity, specificity, positive predictive value and negative predictive value when applied prospectively to the second population. CONCLUSION: Tumour size, LVI, age, nuclear grade, histological subtype, multifocality and location in the breast were independent predictive factors for ALNM in IFDC. ALNM is less frequent in UIQ tumours than in other-quadrant tumours. Our prospectively validated predictive model could be valuable in pre-operative patient discussions, although staging of the axilla in the individual patient remains necessary.

Adult↗
PubMed2002

A selection algorithm for internal mammary sentinel lymph node biopsy in breast cancer.

Internal mammary lymph-node (IMN) metastases in breast carcinomas have a major influence on survival, comparable with the influence of axillary lymph-node metastases (ALNM). Prospective, randomized trials have demonstrated that complete IMN dissection as part of extended radical mastectomy does not improve overall or disease-free survival. In the subset of patients with tumours 1cm or less in size and no ALNM, information on IMN status would provide important information. In these cases, the presence of IMN metastases would change the staging from stage I to stage IIIB, according to the current tumour, node and metastasis classification. More importantly, it would influence these patients' adjuvant treatment. Lymphatic mapping for sentinel lymph-node (SLN) biopsy has demonstrated extra-axillary drainage in up to 35% of patients. Recent reports have demonstrated the feasibility of internal mammary sentinel lymph-node (IM-SLN) biopsy. Here we review the general prognostic and clinical significance of tumor location and lymph-node metastases in breast cancer and discuss the specific factors associated with IMN identification, metastases and treatment in the pre-SLN and SLN eras. Based on our review, we propose an algorithm for a selective approach to IM-SLN in breast cancer.

Algorithms↗
PubMed2001

Is there a role for selective axillary dissection in breast cancer?

Surgery is the most effective therapeutic intervention available for the treatment of breast cancer. It has been responsible for obtaining local control and long-term disease-free intervals in more patients over the past century than any other treatment modality. Trends toward earlier stage at diagnosis are likely to increase the importance of surgery and to secure its central role in the treatment of this disease. Unfortunately, during the 1990s the value of excellent local control of breast cancer has been minimized as the disease has come to be considered systemic from inception and as the results of adjuvant-therapy trials in patients with early-stage breast cancer have revealed survival advantages in patients receiving systemic therapy. Only rarely is it acknowledged that surgery alone achieves long-term disease-free states in 70% to 80% of all patients. At the core of this paradigmatic controversy is management of the axilla. The status of the axilla remains the most powerful predictor of outcome in patients with invasive carcinoma of the breast, and it is likely that a small but identifiable subset of patients obtains a survival benefit from the removal of disease-containing nodes. It is believed that no benefit is derived from the removal of negative nodes, and indeed there are even patients in whom complete elimination of the exploration of the axilla may be considered-all of which underscores the need to investigate the axilla selectively. Lymphatic mapping and sentinel lymph node (SLN) biopsy represents the most exciting development to date toward this end. The challenge today, as we move closer to a selective approach to the axilla, is to ensure that patients with positive nodes have those nodes identified and removed and patients with negative nodes experience minimal disturbance of their axilla.

Axilla↗
PubMed2001

Sentinel lymph node biopsy in patients with male breast carcinoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is now a widely implemented technique for evaluating the axilla in women with early stage breast carcinoma. Men who develop breast carcinoma are at similar risk as their female counterparts of developing the morbidities related to axillary dissection. SLNB is aimed at preventing these morbidities. In this study, the authors evaluated the role of SLNB in the treatment of men with early stage breast carcinoma. METHODS: Among the 1692 patients who underwent SLNB at the Memorial Sloan-Kettering Cancer Center, 16 men with breast carcinoma were identified. The charts and records of these 16 patients were reviewed retrospectively. RESULTS: The mean patient age was 57.2 years. The mean tumor size was 1.3 cm. In 15 of 16 patients (93.75%) and in all patients with T1 tumors, one or more sentinel lymph nodes were successfully identified. SLNB failed in one patient, who had a T2 tumor (3 cm). Ten of the 15 patients had negative sentinel lymph nodes (66.7%). Four of these patients had no additional lymph nodes removed, whereas six patients had additional lymph nodes removed, all of which were negative. Two patients (13.3%) had positive sentinel lymph nodes on frozen-section analysis and underwent immediate completion axillary dissection: Both had additional positive lymph nodes. Three patients (20.0%) had positive sentinel lymph nodes on further sectioning or immunohistochemistry, and two patients underwent completion axillary dissection: Neither patient had additional positive lymph nodes. The third patient had one immunohistochemically positive lymph node and did not undergo completion axillary dissection. CONCLUSIONS: SLNB for patients with breast carcinoma was as successful in men as it has been shown to be in women and may be offered as a management option to men with early stage breast carcinoma by surgeons who are experienced with the technique.

Adult↗
PubMed2001

Lymphovascular invasion enhances the prediction of non-sentinel node metastases in breast cancer patients with positive sentinel nodes.

BACKGROUND: Fifty percent of patients with sentinel lymph node (SLN) metastases have no metastatic disease in non-SLNs on axillary lymph node dissection (ALND). The goal of this study is to determine which patients have metastatic disease limited to the SLN, and, therefore, may not require completion ALND. METHODS: Of the first 1000 patients undergoing SLN biopsy at Memorial Sloan-Kettering Cancer Center, using a combined blue dye and isotope technique, 231 (26%) had positive SLN. Of these, 206 underwent completion ALND. They are the study group for this report. RESULTS: The likelihood of non-SLN metastasis was inversely related to three clinicopathologic variables: tumor size < or = 1.0 cm; absence of lymphovascular invasion (LVI); and SLN micrometastases (< or = 2 mm). None of 24 patients with all three predictive factors had non-SLN metastases, whereas 58% of patients with none of the factors had disease in the non-SLN. CONCLUSION: Patients with small breast cancers, no LVI, and SLN micrometastases have a low risk of non-SLN metastases, and may not require completion ALND.

Adult↗
PubMed2001

Patient reluctance toward tamoxifen use for breast cancer primary prevention.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial demonstrated that tamoxifen reduces the incidence of new breast cancers by 49% in women at increased risk for breast cancer development. Tamoxifen does have side effects, however, including marginally increased risks of endometrial cancer and thromboembolic events. In this study, women at increased risk for breast cancer development were offered tamoxifen. Their knowledge of tamoxifen as a chemopreventive agent was assessed, and factors influencing their acceptance of tamoxifen and willingness to take it were determined. METHODS: Forty-three patients were identified who qualified to take tamoxifen for primary prevention. Patients qualified by having at least a 1.7% 5-year risk of developing breast cancer, the criteria for entry into the NSABP P-1 trial. Patients initially completed questionnaires designed to assess their knowledge of tamoxifen and its associated risks and benefits. Patients were then provided neutral educational sessions and literature delineating the actual risks and benefits of tamoxifen. Subsequently, patients' decisions regarding taking tamoxifen were reassessed. RESULTS: Mean patient age was 52.8 years, with a range of 39 to 74 years. Ten patients (23.2%) qualified based on the presence of lobular carcinoma in situ (LCIS), seven patients (16.3%) qualified based on increased risk secondary to age >60 years, and 26 patients (60.5%) age range 35 to 59 qualified based on risk profiles demonstrating significantly increased risk. Of the total 43 patients, two (4.7%) elected to start taking tamoxifen. Fifteen patients (34.8%) declined immediately, and 26 patients (60.5%) were undecided initially but ultimately declined. Educational sessions did not influence patients' decisions. Fear of side effects, including endometrial cancer, thromboembolic events, and menopausal symptoms, was the most commonly cited reason for declining to take tamoxifen. CONCLUSIONS: In this study, the vast majority of patients at increased risk for breast cancer perceived that the risks of taking tamoxifen outweighed the benefits and declined to take it.

Adult↗
PubMed2001

Highest isotope count does not predict sentinel node positivity in all breast cancer patients.

BACKGROUND: Radioisotope mapping is an essential technical component of sentinel lymph node (SLN) biopsy, and most authors define isotope success by an arbitrary threshold SLN-to-background ratio. Few studies have examined the degree to which the relative level of SLN counts correlates with the presence of metastasis. Having removed the SLN with the highest counts, how far should the surgeon persist in removing additional SLN which contain much lower levels of isotope? METHODS: We performed SLN biopsy, using both radioisotope and blue dye, in 2285 consecutive patients with stage I-II breast cancer. Successful isotope localization was defined as an ex vivo SLN-to-axillary background count ratio of at least 4:1, and enhanced pathologic analysis (serial sections and immunohistochemistry) was used throughout. RESULTS: Among the 1566 patients with more than one SLN site identified, the SLN contained metastasis in 463 (30%). In 369 (80%) of these SLN-positive cases, the SLN with the highest count contained tumor, but in 94 (20%) it was benign. Among these 94: (1) the counts of the hottest benign SLN exceeded those of the histologically positive SLN by a ratio of at least 10:1 in 31% (29 of 94) of cases, (2) the counts of the positive SLN were < 4:1 those of the axillary background in 16% (15 of 94) of cases, and (3) blue dye failed to identify 27% of positive SLN. No optimum ratio of SLN-to-SLN or SLN-to-background counts identified the positive SLN in all cases. CONCLUSION: Although the SLN with the highest counts is positive in 80% of breast cancer patients with multiple SLN, neither a relatively high isotope count nor the presence of blue dye consistently predict SLN positivity in all breast cancer patients. For maximum accuracy, SLN biopsy requires (1) the removal of all nodes containing isotope regardless of the relative magnitude of counts, (2) the concurrent use of blue dye to salvage those procedures in which isotope fails, and (3) the removal of all clinically suspicious non-SLN.

Adolescent↗
PubMed2001

Localization of the sentinel node in breast cancer: identical results with same-day and day-before isotope injection.

BACKGROUND: Although the technique of sentinel lymph node (SLN) biopsy in breast cancer is not fully standardized, an increasing number of centers map the SLN by using radioisotope supplemented by blue dye, and most have injected isotope on the day of surgery. Here we directly compare the results of same-day and day-before isotope injection in a large series of breast cancer patients having SLN biopsy with our mature technique. METHODS: Starting with our 961st SLN procedure for breast cancer, 1320 consecutive patients had SLN biopsy after the injection of unfiltered 99mTc-labeled sulfur colloid given as a single-site, low-volume (0.05 ml) intradermal injection: 933 on the day of surgery (1-day protocol) and 387 on the day before (2-day protocol). All had intraparenchymal injection of blue dye. RESULTS: The two groups were comparable in age, tumor location, histopathologic characteristics, and number of SLNs identified. LSG taken at 2 hours in the 2-day protocol was positive more often than LSG performed at 30 minutes in the 1-day protocol, and nonaxillary sites of lymphatic drainage were seen in <1% of each group. Absolute isotope counts and the ratio of SLN to axillary background counts were similar. Isotope localization of the SLN succeeded in a comparable fraction of patients, as did SLN identification overall. CONCLUSIONS: The results of SLN mapping with same-day and day-before injection of radioisotope are virtually identical. The logistical advantages of day-before injection do not compromise the success of the procedure.

Adult↗
PubMed2001

Molecular analysis of the INK4A and INK4B gene loci in human breast cancer cell lines and primary carcinomas.

The INK4A and INK4B loci are located at 9p21 and have been implicated in the tumorigenesis of various human malignancies. The INK4A gene encodes two cell cycle regulators, p16(INK4A) and ARF, while INK4B encodes p15(INK4B). Previously, we have shown that the p16(INK4) tumor suppressor was not mutated or deleted in primary breast carcinomas. However, primary and metastatic breast carcinomas exhibited a relative hypomethylation of p16(INK4A), which is associated with expression, compared to normal breast tissue. The present study was conducted to determine if inactivation of p15(INK4B) and INK4A exon 1beta (ARF) are common events in breast carcinoma. Mutational analysis was performed by PCR-SSCP, and mRNA expression was evaluated by RT-PCR. Methylation-specific PCR was used to determine the methylation status of the p15(INK4B) promoter. Our results demonstrate that the p15(INK4B) gene was altered in 3 (21%) of the 14 breast cell lines; one had a silent mutation and two had homozygous deletion of the gene. None of the cell lines showed methylation of p15(INK4B). Two (14%) cell lines had homozygous deletion of INK4A exon 1beta. All normal and malignant breast tissue samples were wild-type and non-methylated for p15(INK4B) and wild-type for exon 1beta. Our results show that these structurally and functionally related genes are not invariably affected together, and the most frequently observed alteration at the INK4A and INK4B loci in breast carcinoma appears to be p16(INK4A) hypomethylation.

Blotting, Southern↗
PubMed2001

The breast cancer patient with multiple sentinel nodes: when to stop?

BACKGROUND: During sentinel lymph node (SLN) biopsy for breast cancer, most authors report identifying a mean of 1 to 3 SLNs, but a range of 1 to 8 (or more) SLNs per patient. A significant minority of patients have 4 or more SLNs. Here we seek to determine the significance for the breast cancer patient of finding multiple SLNs, and whether there is an optimal threshold number of SLNs that should be removed. STUDY DESIGN: 1,561 patients who underwent successful SLN biopsy using blue dye and radioisotope in combination. Each SLN site was categorized prospectively by the operating surgeon as a dye success, an isotope success, or both. All SLNs containing counts at least four times greater than the postexcision axillary background were considered to be isotope successes. RESULTS: Fifteen percent of patients (241) had multiple (>3) SLNs. Ninety-eight percent of node-positive patients (440 of 449) were identified within the first three SLN sites examined. In 2% of all SLN positive patients (9 of 449) or 4% of patients with multiple SLN (9 of 241), a positive SLN was detected at site four or more. In eight patients the first positive SLN was found at sites four or more. Blue dye and isotope were equally effective in identifying metastases in patients with multiple SLNs. CONCLUSIONS: Fifteen percent of patients having SLN biopsy for breast cancer have multiple SLNs. Although 98% of positive SLNs were identified within the first three sites sampled, a small number of patients had their first positive SLN at sites 4 to 8. These data suggest that there is no absolute upper threshold for the number of SLNs that should be removed. Sampling a few additional SLNs probably adds little morbidity to the procedure, yet may significantly alter the treatment of some individuals. SLN biopsy should be continued until all blue and hot nodes are removed.

Breast Neoplasms↗
PubMed2001

A trend analysis of the relative value of blue dye and isotope localization in 2,000 consecutive cases of sentinel node biopsy for breast cancer.

BACKGROUND: Among the advocates of blue dye, isotope, or combined dye-isotope mapping of the sentinel lymph node (SLN) for breast cancer, there is no universal consensus as to which technique is optimal and whether the relative value of each method changes with increasing experience. The objective of this study was to examine the relative contributions of blue dye and radioisotope to successful identification of the SLN as the SLN-mapping technique evolved over our first 2,000 consecutive cases. STUDY DESIGN: Using the first 2,000 consecutive SLN biopsy procedures for breast cancer, performed by eight surgeons (none previously experienced in SLN techniques) at one institution, using a combined technique of blue dye and isotope mapping, we report the institutional learning curve and the relative contributions of dye and isotope to identifying both the SLN and the positive SLN, by increments of 500 cases. RESULTS: Comparing the first 500 with the most recent 500 cases, success in identifying the SLN by blue dye did not improve with experience, although success in isotope localization steadily increased, from 86% to 94% (p < 0.00005). With the increasing success of isotope mapping, the marginal benefit of blue dye (the proportion of cases in which the SLN was identified by blue dye alone) steadily declined, from 9% to 3% (p = 0.0001). Parallel to this trend, the proportion of positive SLNs identified by blue dye did not change with experience (89% to 90%), but isotope success steadily increased, from 88% to 98% (p = 0.0015). The proportion of positive SLNs identified by blue dye alone declined from 12% to 2% (p = 0.0015). CONCLUSIONS: Using a combined technique of blue dye and radioisotope mapping, and with refinement of the radioisotope technique, we report 97% success identifying the SLN. Although we continue to recommend the use of both methods in SLN mapping for breast cancer, we observe with experience a declining marginal benefit for blue dye.

Breast Neoplasms↗
PubMed2001

Genetic alterations of the p14ARF -hdm2-p53 regulatory pathway in breast carcinoma.

TP53 is the most commonly mutated tumor suppressor gene in human cancers. The amplification and overexpression of HDM2 plays a role in tumorigenesis via inactivation of p53-dependent cell cycle arrest. p14ARF, an alternate transcript of the INK4A tumor suppressor locus, prevents hdm2-induced transcriptional silencing of p53 by binding hdm2. The role of this p14ARF-hdm2-p53 regulatory pathway in breast carcinoma is unknown. We hypothesized that p14ARF mutations and HDM2 gene amplification may be alternative mechanisms of p53 inactivation in breast cancer. Mutational analysis of TP53 (exons 5-9) and exon 1beta of pl4ARF was performed by PCR-SSCP and putative mutations were confirmed by sequencing. p14ARF mRNA expression was evaluated by RT-PCR and the presence of HDM2 gene amplification by differential PCR. Among the cell lines, 7/14 (50%) harbored TP53 mutations and 2/14 (14%) had a deletion ofp14ARF exon 1beta with no detectable p14ARF mRNA. None demonstrated HDM2 gene amplification. TP53 mutations were identified in 7/36 (19%) breast tumors and HDM2 amplification in 2/30 (7%) tumors. All the tumors contained an intact p14ARF exon 1beta with corresponding expression of the mRNA. Alterations in the various components of this regulatory pathway were identified in nine (64%) cell lines and 25% of the 36 breast cancers with TP53 mutation being the predominant aberration. Although p14ARF mutations and HDM2 gene amplification appear to be uncommon events in breast carcinoma, deregulation of this pathway may occur via alternative mechanisms in breast carcinogenesis.

Breast Neoplasms↗
PubMed2001

Sentinel lymph node biopsy: an American perspective.

The current protocol for use of sentinel lymph node biopsy at Memorial Sloan-Kettering Cancer Center, NY, USA is described. The technique requires to be validated both by individual surgeons and institutions prior to use. Ongoing American multi-institutional trials to investigate the true role of sentinel lymph node biopsy are underway.

Journal Article↗