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1.
Ann Surg Oncol ; 14(3): 1020-3, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17195914

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Paget's Disease, Mammary/secondary , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Retrospective Studies
3.
Ann Surg Oncol ; 10(9): 1048-53, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14597443

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Lobular/pathology , Magnetic Resonance Imaging , Neoplasms, Second Primary/pathology , Biopsy/methods , Breast Neoplasms/diagnosis , Carcinoma, Lobular/diagnosis , Female , Humans , Middle Aged , Neoplasms, Second Primary/diagnosis , Patient Selection , Retrospective Studies , Sensitivity and Specificity
4.
Eur J Surg Oncol ; 28(6): 603-14, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12359195

ABSTRACT

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.


Subject(s)
Algorithms , Breast Neoplasms/pathology , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Female , Humans , Lymphatic Metastasis , Mammary Arteries , Neoplasm Staging , Patient Selection , Prognosis , Women's Health
5.
Eur J Surg Oncol ; 28(5): 490-500, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12217300

ABSTRACT

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.


Subject(s)
Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Axilla , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Lobular/diagnosis , Female , Humans , Middle Aged , Multivariate Analysis , Neoplasm Staging , Predictive Value of Tests , Retrospective Studies , Selection Bias , Sensitivity and Specificity , Women's Health
6.
J Am Coll Surg ; 193(5): 473-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11708502

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Rosaniline Dyes , Sentinel Lymph Node Biopsy/methods , Technetium Tc 99m Sulfur Colloid , Breast Neoplasms/surgery , Dose-Response Relationship, Radiation , Female , Humans , Injections, Intralesional , Lymph Node Excision , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Neoplasm Staging , Predictive Value of Tests , Radionuclide Imaging , Retrospective Studies
7.
Genet Med ; 3(6): 422-5, 2001.
Article in English | MEDLINE | ID: mdl-11715007

ABSTRACT

PURPOSE: Risk-reducing surgery is an important option for women with BRCA1 and BRCA2 mutations. There are reports in the literature that insurance reimbursement for these procedures varies greatly. Because health insurance coverage significantly affects medical decision-making, current information regarding reimbursement practices of third-party payers is needed. METHODS: Retrospective study of hospital billing records of 38 women with documented BRCA1 or BRCA2 mutations who underwent either a risk-reducing mastectomy or a risk-reducing oophorectomy between March 1, 1997, and July 30, 2000. RESULTS: Complete billing and reimbursement information was available for 35 women undergoing a total of 39 risk-reducing surgeries. A total of 38 of 39 (97%) risk-reducing surgeries were covered in full, less applicable coinsurance and deductibles. The rate of insurance reimbursement did not vary with type of insurance, personal history of cancer, or type of procedure. CONCLUSION: Insurance carriers reimbursed the vast majority of BRCA mutation carriers undergoing risk-reducing surgery.


Subject(s)
Breast Neoplasms/prevention & control , Insurance Coverage/statistics & numerical data , Insurance, Health, Reimbursement/statistics & numerical data , Mastectomy/economics , Ovarian Neoplasms/prevention & control , Ovariectomy/economics , Adult , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Breast Neoplasms/surgery , Decision Making , Female , Genes, BRCA1 , Genetic Counseling , Genetic Predisposition to Disease , Heterozygote , Hospital Records , Humans , Managed Care Programs/economics , Middle Aged , Mutation , New York , Ovarian Neoplasms/genetics , Ovarian Neoplasms/surgery , Retrospective Studies , Risk Factors
9.
Ann Surg Oncol ; 8(8): 682-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11569785

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Carcinoma/pathology , Carcinoma/secondary , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy/methods , Adult , Aged , Biopsy, Needle , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Carcinoma/diagnostic imaging , Carcinoma/surgery , Female , Humans , Injections, Intradermal , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Preoperative Care , Probability , Prospective Studies , Radionuclide Imaging , Sensitivity and Specificity , Technetium/administration & dosage , Time Factors
10.
Surgery ; 130(3): 432-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11562666

ABSTRACT

BACKGROUND: The optimal sentinel lymph node (SLN) biopsy technique remains undefined in breast cancer. Injecting radiotracer or blue dye by a variety of routes seems to stage the axilla with comparable accuracy, and we have hypothesized that the dermal and the parenchymal lymphatics of the breast drain to the same SLN in most patients. Two previous studies from our institution support this concept: (1) a single-surgeon series of 200 consecutive SLN biopsy procedures demonstrating a high dye-isotope concordance for both intradermal (ID) and intraparenchymal (IP) isotope injection, and (2) a series of 100 procedures validated by a backup axillary dissection (ALND) in which the false-negative rate following ID isotope injection was comparable to that of our previous results with IP injection. Here, we directly compare the results of SLN biopsy using either ID or IP isotope injection for our entire experience of SLN biopsy procedures in which a backup ALND was done. METHODS: This is a retrospective, nonrandomized study of 298 clinical stage I to II breast cancer patients having SLN biopsy with a backup ALND planned in advance, comparing the results of ID (n = 164) and IP (n = 134) isotope injection. All patients had IP injection of blue dye. Endpoints included (1) successful SLN identification, (2) false-negative rate, (3) dye-isotope concordance, and (4) the SLN/axillary background isotope count ratio. RESULTS: ID isotope was more successful than IP, identifying the SLN in 98% versus 89% of cases, respectively. False-negative results (4.8% vs 4.4%) and dye-isotope concordance (92% vs 93%) were comparable between the 2 groups, and SLN/axillary background isotope count ratios were significantly higher with ID than with IP injection (288/1 vs 59/1). CONCLUSIONS: ID isotope injection identifies the SLN more often than IP, stages the axilla with comparable accuracy, and is associated with higher levels of SLN isotope uptake. The dermal and parenchymal lymphatics of the breast drain to the same axillary SLN in most breast cancer patients, and ID isotope injection is the procedure of choice in this setting.


Subject(s)
Breast Neoplasms/pathology , Breast/pathology , Radioisotopes/administration & dosage , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Axilla/surgery , False Negative Reactions , Female , Humans , Injections , Injections, Intradermal , Lymph Node Excision , Male , Middle Aged , Neoplasm Staging , Retrospective Studies
11.
Ann Surg Oncol ; 8(7): 580-5, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11508619

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/prevention & control , Tamoxifen/therapeutic use , Adult , Aged , Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/psychology , Carcinoma in Situ/prevention & control , Carcinoma in Situ/psychology , Carcinoma, Lobular/prevention & control , Carcinoma, Lobular/psychology , Female , Health Knowledge, Attitudes, Practice , Humans , Middle Aged , Surveys and Questionnaires , Tamoxifen/adverse effects , Treatment Refusal/psychology
12.
Ann Surg Oncol ; 8(7): 592-7, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11508621

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnostic imaging , Child , Female , Humans , Lymphatic Metastasis/diagnostic imaging , Male , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals , Rosaniline Dyes , Sentinel Lymph Node Biopsy/methods , Technetium Tc 99m Sulfur Colloid
13.
Clin Cancer Res ; 7(8): 2434-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11489823

ABSTRACT

PURPOSE: Clinically undetectable micrometastases may account for disease recurrence in breast cancer patients after variable disease-free intervals. However, little is known about the cellular mechanisms controlling human breast cancer micrometastases. We compared tumor proliferation rate, apoptotic index, and angiogenesis in human breast cancer micrometastases with those of macroscopic axillary lymph node metastases. EXPERIMENTAL DESIGN: Seven breast cancer micrometastases (<2 mm) obtained from the sentinel nodes of seven patients were compared with 13 macrometastases (lymph node replaced with tumor) obtained from 13 patients. The tissue was fixed in formalin, embedded in paraffin, serially sectioned, and evaluated by H&E and immunohistochemistry for cytokeratin. Tumor proliferation rate was assessed as the number of Ki-67-positive nuclei/total number of tumor nuclei. Tumor vascularity was quantified using antibody to factor VIII to identify microvessels per high-power field (at x400). Apoptosis was quantified using the terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling method. Results were analyzed with the Wilcoxon rank-sum test. RESULTS: Median size of micrometastases was 0.5 mm (range, 0.4-1.0), and the median number of tumor nuclei/section was 143 (range, 90-312). Median proliferation rate for macrometastases was greater than for micrometastases (35% versus 12%; P = 0.003). Median microvessel density/high-power field for macrometastases was greater than for micrometastases (17 versus 1; P < 0.001). There was no difference in apoptotic index between macrometastases and micrometastases (1.1% versus 0.7%; P = not significant). CONCLUSIONS: Human breast cancer micrometastases have lower tumor proliferation rates and angiogenesis than breast cancer macrometastases. These characteristics may explain their differential growth patterns.


Subject(s)
Breast Neoplasms/pathology , Neoplasm Metastasis/pathology , Adult , Aged , Apoptosis , Breast Neoplasms/blood supply , Breast Neoplasms/metabolism , Cell Division , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Middle Aged , Neovascularization, Pathologic/pathology , von Willebrand Factor/analysis
14.
J Am Coll Surg ; 192(6): 692-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11400962

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Carcinoma in Situ/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Lymphatic Metastasis/pathology , Neoplasm Staging/methods , Neoplasm Staging/standards , Patient Selection , Sentinel Lymph Node Biopsy/methods , Sentinel Lymph Node Biopsy/standards , Female , Humans , Male , Middle Aged , Prospective Studies , Radiopharmaceuticals , Rosaniline Dyes , Sensitivity and Specificity , Technetium Tc 99m Sulfur Colloid
15.
Breast Cancer Res Treat ; 65(3): 225-32, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11336244

ABSTRACT

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.


Subject(s)
Breast Neoplasms/genetics , Carcinoma/genetics , Gene Amplification , Gene Expression Regulation, Neoplastic , Genes, p53/genetics , Nuclear Proteins , Proteins/genetics , Proto-Oncogene Proteins/genetics , Breast Neoplasms/pathology , Carcinoma/pathology , Cell Cycle , Cell Transformation, Neoplastic , DNA Mutational Analysis , Exons , Female , Humans , Proto-Oncogene Proteins c-mdm2 , RNA, Messenger , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Tumor Suppressor Protein p14ARF
17.
World J Surg ; 25(6): 809-18, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11376420

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Lymph Node Excision/methods , Axilla , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Neoplasm Staging , Prognosis , Sentinel Lymph Node Biopsy
18.
Cancer Genet Cytogenet ; 125(2): 131-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11369056

ABSTRACT

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.


Subject(s)
Breast Neoplasms/genetics , Carcinoma/genetics , Carrier Proteins/genetics , Cell Cycle Proteins , Chromosomes, Human, Pair 9/genetics , DNA Methylation , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Genes, p16 , Tumor Suppressor Proteins , Blotting, Southern , Breast/metabolism , Breast Neoplasms/pathology , Carcinoma/pathology , Carrier Proteins/biosynthesis , CpG Islands , Cyclin-Dependent Kinase Inhibitor p15 , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , DNA Mutational Analysis , DNA, Neoplasm/genetics , Exons/genetics , Female , Gene Expression Profiling , Gene Silencing , Humans , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Polymorphism, Single-Stranded Conformational , RNA, Messenger/biosynthesis , RNA, Neoplasm/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Sequence Deletion , Tumor Cells, Cultured , Viral Proteins/biosynthesis , Viral Proteins/genetics
19.
Ann Surg Oncol ; 8(2): 145-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11258779

ABSTRACT

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.


Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Analysis of Variance , Axilla , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/secondary , Carcinoma, Ductal, Breast/surgery , Female , Frozen Sections , Humans , Lymph Node Excision/methods , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Radionuclide Imaging , Sensitivity and Specificity
20.
Cancer ; 91(2): 319-23, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11180077

ABSTRACT

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.


Subject(s)
Breast Neoplasms, Male/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Papillary/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Humans , Lymph Node Excision , Male , Middle Aged , Retrospective Studies
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