-
Nicolaos Palaskas,
Steven M Larson,
Nikolaus Schultz,
Evangelia Komisopoulou,
Justin Wong,
Dan Rohle,
Carl Campos,
Nicolas Yannuzzi,
Joseph R Osborne,
Irina Linkov, [......],
Chris Tran,
Adriana Heguy,
Hong Wu,
Chris Sander,
Michael E Phelps,
Cameron Brennan, Elisa Port,
Jason T Huse,
Thomas G Graeber,
Ingo K Mellinghoff
[show abstract]
[hide abstract]
ABSTRACT: In contrast to normal cells, cancer cells avidly take up glucose and metabolize it to lactate even when oxygen is abundant, a phenomenon referred to as the Warburg effect. This fundamental alteration in glucose metabolism in cancer cells enables their specific detection by positron emission tomography (PET) following i.v. injection of the glucose analogue (18)F-fluorodeoxy-glucose ((18)FDG). However, this useful imaging technique is limited by the fact that not all cancers avidly take up FDG. To identify molecular determinants of (18)FDG retention, we interrogated the transcriptomes of human-cancer cell lines and primary tumors for metabolic pathways associated with (18)FDG radiotracer uptake. From ninety-five metabolic pathways that were interrogated, the glycolysis, and several glycolysis-related pathways (pentose phosphate, carbon fixation, aminoacyl-tRNA biosynthesis, one-carbon-pool by folate) showed the greatest transcriptional enrichment. This "FDG signature" predicted FDG uptake in breast cancer cell lines and overlapped with established gene expression signatures for the "basal-like" breast cancer subtype and MYC-induced tumorigenesis in mice. Human breast cancers with nuclear MYC staining and high RNA expression of MYC target genes showed high (18)FDG-PET uptake (P < 0.005). Presence of the FDG signature was similarly associated with MYC gene copy gain, increased MYC transcript levels, and elevated expression of metabolic MYC target genes in a human breast cancer genomic dataset. Together, our findings link clinical observations of glucose uptake with a pathologic and molecular subtype of human breast cancer. Furthermore, they suggest related approaches to derive molecular determinants of radiotracer retention for other PET-imaging probes.
Cancer Research 06/2011; 71(15):5164-74. · 7.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PET imaging is useful for evaluating locally advanced primary breast cancer. Expression of specific molecular markers in these cancers, such as estrogen receptor (ER), progesterone receptor (PR), and HER2 status, has direct prognostic and therapeutic implications in patient management. This study aimed to determine whether a relationship exists between tumor glucose use and important molecular markers in invasive breast cancer. For our purposes, tumor glucose use is quantified by the PET-derived parameter maximum standardized uptake value (SUV).
Breast tumors from 36 patients were excised and examined histologically after PET. ER, PR, and HER2 status were determined for all lesions histopathologically. In addition, genomewide expression for a subset of 20 tumors was analyzed using the human genome U133A oligonucleotide microarray.
A significant association was found between estrogen ER status and lesion SUV. ER-negative tumors (n = 17; median SUV, 8.5) demonstrated a significantly higher maximum SUV than did ER-positive tumors (n = 19; median SUV, 4.0) (P < 0.001). No significant association existed between SUV and PR status, HER2/neu status, lymph node involvement, or tumor size. Unsupervised hierarchic clustering of the 20 genetically profiled cancers segregated tumor samples into 2 primary groups of 10 patients each, largely corresponding to ER status.
In locally invasive primary breast cancer, ER-negative tumors display higher (18)F-FDG uptake than ER-positive tumors. Microarray analysis confirms these data and identifies genes associated with increased glucose use as measured by PET. These genes significantly overlap those of a previously validated ER-status molecular phenotype. These preliminary data support a growing body of evidence that ER-positive and ER-negative breast cancers have distinct disease-specific patterns. Further validation prospectively and with larger numbers will be required to establish a robust molecular signature for metabolic uptake and patterns of aggressive behavior in advanced breast cancer.
Journal of Nuclear Medicine 03/2010; 51(4):543-50. · 6.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Positron emission tomography (PET) scanning is now part of the standard evaluation for patients with a variety of different malignancies. We describe our experience with breast incidentalomas in a large series of PET scans performed for patients without a known history of breast cancer.
From March 2000 through June 2007, approximately 45,000 PET scans were performed; 163 had breast findings unrelated to the primary malignancy. In 103 of 163 (63%), findings included physiologic variation, lactation, implants, or benign calcifications. Chart review was conducted in the remaining 60 of 163 patients (37%).
In 20 of 60 patients (33%), no additional evaluation was performed due to advanced stage of the primary malignancy; 40 of 60 (67%) underwent additional imaging and evaluation. In 16 of 40 patients (40%), the lesion resolved on repeat PET; the lesion persisted in 10 of 40 (25%). Additional breast imaging was performed in 14 of 40 (35%). In total, 12 of 40 (30%) underwent biopsy; 7 of 40 (18%) were positive for malignancy.
In our experience, 29% of breast incidentalomas (7 of 24) with persistent imaging findings were malignant. Further evaluation of these lesions should be based on overall clinical status. In patients where results would not change overall management, biopsy may not be warranted.
Annals of Surgical Oncology 02/2010; 17(8):2119-25. · 4.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Completion axillary lymph node dissection (CALND) is routinely performed in breast cancer patients with positive sentinel lymph nodes (SLN). We sought to determine the sociodemographic, pathologic, and therapeutic variables that were associated with CALND.
From 7/1997 to 7/2003, 1,470 patients with invasive breast cancer were SLN positive by intraoperative frozen section or final pathologic exam by hematoxylin-eosin and/or immunohistochemistry (IHC). A comorbidity score was assigned using Adult Comorbidity Evaluation-27 system. Fisher's exact, Wilcoxon tests, and multivariate logistic regression analysis were used.
CALND was performed less often in patients with age >or= 70 years compared with age < 70 years, moderate or severe comorbidities compared with no or mild, IHC-only positive SLN and breast conservation therapy (BCT compared with mastectomy. Patients who did not undergo CALND were less likely than CALND patients to have grade III disease, lymphovascular invasion multifocal disease, tumor size > 2 cm or to receive adjuvant chemotherapy. However, they were more likely to undergo axillary radiotherapy (RT). On multivariate analysis, age >or= 70 years [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.26-0.63], IHC-only positive SLN (OR 0.13, 95%CI 0.09-0.19), presence of moderate to severe comorbidities (OR 0.64, 95%CI 0.41-0.99), tumor size <or= 2 cm (OR 0.44, 95%CI 0.29-0.66), axillary RT (OR 0.39, 95%CI 0.20-0.78), and BCT (OR 0.54, 95%CI 0.37-0.79) were all independently associated with lower odds of CALND.
The decision to perform CALND following positive SLN biopsy was multifactorial. Patient factors were a primary determinant for the use of CALND in our study. The decreased use of CALND in the BCT patients probably reflects reliance on the radiotherapy tangents to maintain local control in the axilla.
Annals of Surgical Oncology 05/2009; 16(7):1952-8. · 4.17 Impact Factor
-
Arpana M Naik,
Jane Fey,
Mary Gemignani,
Alexandra Heerdt,
Leslie Montgomery,
Jeanne Petrek, Elisa Port,
Virgilio Sacchini,
Lisa Sclafani,
Kimberly VanZee,
Raquel Wagman,
Patrick I Borgen,
Hiram S Cody
[show abstract]
[hide abstract]
ABSTRACT: We sought to identify the rate of axillary recurrence after sentinel lymph node (SLN) biopsy for breast cancer.
SLN biopsy is a new standard of care for axillary lymph node staging in breast cancer. Nevertheless, most validated series of SLN biopsy confirm that the SLN is falsely negative in 5-10% of node-positive cases, and few studies report the rate of axillary local recurrence (LR) for that subset of patients staged by SLN biopsy alone.
Through December of 2002, 4008 consecutive SLN biopsy procedures were performed at Memorial Sloan-Kettering Cancer Center for unilateral invasive breast cancer. Patients were categorized in 4 groups: SLN-negative with axillary lymph node dissection (ALND; n = 326), SLN-negative without ALND (n = 2340), SLN-positive with ALND (n = 1132), and SLN-positive without ALND (n = 210). Clinical and pathologic characteristics and follow-up data for each of the 4 cohorts were evaluated with emphasis on patterns of axillary LR.
With a median follow-up of 31 months (range, 1-75), axillary LR occurred in 10/4008 (0.25%) patients overall. In 3 cases (0.07%) the axillary LR was the first site of treatment failure, in 4 (0.1%) it was coincident with breast LR, and in 3 (0.07%) it was coincident with distant metastases. Axillary LR was more frequent among the unconventionally treated SLN-positive/no ALND patients than in the other 3 conventionally treated cohorts (1.4% versus 0.18%, P = 0.013).
Axillary LR after SLN biopsy, with or without ALND, is a rare event, and this low relapse rate supports wider use of SLN biopsy for breast cancer staging. There is a low-risk subset of SLN-positive patients in whom completion ALND may not be required.
Annals of Surgery 10/2004; 240(3):462-8; discussion 468-71. · 7.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In the United States, identification of the sentinel lymph node (SLN) requires the use of (99m)Tc-labeled colloid, 1% isosulfan blue dye, or both to trace the lymphatic drainage of a given neoplasm. We report our experience with adverse reactions to isosulfan blue dye during SLN mapping in breast cancer. A chart review of the breast cancer SLN database was performed; it included 2392 sequential patients who underwent SLN biopsy involving isosulfan blue dye at Memorial Sloan-Kettering Cancer Center from September 12, 1996, to August 17, 2000. Thirty-nine of 2392 patients (1.6%) had a documented allergic reaction during the mapping procedure. Most reactions (69%) produced urticaria, blue hives, a generalized rash, or pruritus. The incidence of hypotensive reactions was 0.5%. Although anaphylaxis after the injection of isosulfan blue dye is rare, this article highlights the need to suspect anaphylaxis when hemodynamic instability occurs after the injection of this compound. Our experience indicates that bronchospasm and respiratory compromise are unusual and that most patients do not require emergent intubation and can be managed with short-term pressor support. In addition, our data indicate that patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye. IMPLICATIONS: We report the largest single-institution review of adverse reactions to injection of isosulfan blue dye during sentinel lymph node mapping in breast cancer. Bronchospasm and respiratory compromise are unusual, and most patients can be treated with short-term pressor support. Patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye.
Anesthesia & Analgesia 09/2002; 95(2):385-8, table of contents. · 3.29 Impact Factor
