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Expression of DNA Methyltransferases in Breast Cancer Patients and to Analyze the Effect of Natural Compounds on DNA Methyltransferases and Associated Proteins.

Sameer MIRZA ; Gayatri SHARMA ; Rajinder PARSHAD ; Sidhartha Datta GUPTA ; Pranav PANDYA ; Ranju RALHAN

Journal of Breast Cancer.2013;16(1):23-31. doi:10.4048/jbc.2013.16.1.23

PURPOSE: The DNA methylation mediated by specific DNA methyltransferases (DNMTs), results in the epigenetic silencing of multiple genes which are implicated in human breast cancer. We hypothesized that the natural compounds modulate the expression of DNMTs and their associated proteins in the breast cancer cell lines and affect the methylation mediated gene silencing. METHODS: The DNMTs transcript expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in the tumors and the adjacent normal breast tissues of the patients with invasive ductal breast carcinoma. We tested the hypothesis that the natural compounds, viz., epigallocatechin gallate (EGCG), genistein, withaferin A, curcumin, resveratrol, and guggulsterone, have demethylation potential. To investigate this hypothesis, we analyzed the DNMTs expression at the transcript levels, followed by the analysis of DNMT1 and its associated proteins (HDAC1, MeCP2, and MBD2). RESULTS: The increased DNMTs transcripts expression, viz., DNMT1, DNMT3a, and DNMT3b, in the breast cancer tissues suggest involvement of the DNMTs in the breast carcinogenesis. Quantitative RT-PCR analysis revealed that the treatment with natural compounds, viz., EGCG, genistein, withaferin A, curcumin, resveratrol, and guggulsterone, resulted in a significant decrease in the transcript levels of all the DNMTs investigated. Importantly, these natural compounds decreased the protein levels of DNMT1, HDAC1, and MeCP2. CONCLUSION: Our results demonstrate that the natural compounds, EGCG, genistein, withaferin A, curcumin, resveratrol, and guggulsterone, have the potential to reverse the epigenetic changes. Moreover, their lack of toxicity makes these natural compounds promising candidates for the chemoprevention of the breast cancer. In-depth future mechanistic studies aimed to elucidate how these compounds affect the gene transcription are warranted.
Breast ; Breast Neoplasms ; Catechin ; Cell Line ; Chemoprevention ; Curcumin ; DNA ; DNA Methylation ; Epigenomics ; Genistein ; Humans ; Methylation ; Methyltransferases ; Pregnenediones ; Proteins ; Stilbenes ; Withanolides

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The Role of the CDH1 Promoter Hypermethylation in the Axillary Lymph Node Metastasis and Prognosis.

Seung Pil JUNG ; Sangmin KIM ; Seok Jin NAM ; Insun KIM ; Jeoung Won BAE

Journal of Breast Cancer.2013;16(1):16-22. doi:10.4048/jbc.2013.16.1.16

PURPOSE: Hypermethylation of the tumor suppressor genes is frequently observed in the tumor development and progression. However, the correlation between the hypermethylation of the tumor suppressor genes, CDH1 and the axillary lymph node (ALN) metastasis is not fully elucidated. To verify the role of the CDH1 promoter hypermethylation in the ALN metastasis and prognosis, we compared the methylation status of the CDH1 genes in the primary lesion and the paired metastatic ALNs. METHODS: We selected a total of 122 paraffin-embedded specimens of the primary and paired metastatic lymph node from 61 breast cancer patients and analyzed the frequency of hypermethylation in the primary and metastatic lymph node using the methylation-specific polymerase chain reaction. In addition, the methylation status of CDH1 was analyzed with the clinicopathologic characteristics, the disease-free survival and disease-specific survival. RESULTS: The hypermethylation of CDH1 gene was identified in 54 (88.5%) of the 61 patients who had axillary metastasis. The hypermethylation status of the CDH1 gene was significantly increased in the metastatic ALNs compared with that in the primary tumors (60.7% vs. 45.9%, p<0.001). The hypermethylation status of the CDH1 genes in the metastatic ALNs was associated with a poor histologic grade (p=0.041) and the patients who had methylated tumor in the primary lesion showed worse disease-free survival than the patients who did not have methylated tumor (p=0.046). CONCLUSION: This study suggests that hypermethylation of the CDH1 gene may play a pivotal role in the metastasis of the axillary lymph node and the breast cancer recurrence.
Breast Neoplasms ; Disease-Free Survival ; Genes, Tumor Suppressor ; Humans ; Lymph Nodes ; Methylation ; Neoplasm Metastasis ; Polymerase Chain Reaction ; Prognosis ; Recurrence

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Eribulin for Advanced Breast Cancer: A Drug Evaluation.

Alaaeldin SHABLAK

Journal of Breast Cancer.2013;16(1):12-15. doi:10.4048/jbc.2013.16.1.12

Eribulin is a synthetic microtubule dynamics inhibitor that was developed from a marine natural product halichondrin B. It exhibited in vitro and in vivo activities against a wide number of malignancies. A number of advanced phase trials showed improved survival following eribulin treatment in pretreated advanced breast cancer patients. This review provides an overview of the background to the therapeutic use of eribulin in oncology, including its pharmacology, pharmacokinetics, clinical efficacy, safety, and potential economic factors.
Breast ; Breast Neoplasms ; Drug Evaluation ; Ethers, Cyclic ; Furans ; Humans ; Ketones ; Macrolides ; Microtubules

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Potential Applications of Quantum Dots in Mapping Sentinel Lymph Node and Detection of Micrometastases in Breast Carcinoma.

Feroz ALAM ; Neha YADAV

Journal of Breast Cancer.2013;16(1):1-11. doi:10.4048/jbc.2013.16.1.1

Breast cancer cure aims at complete elimination of malignant cells and essentially requires detection and treatment of any micrometastases. Here, we present a review of the current methods in use and the potential role of the quantum dots (QDs) in detection and visualization of sentinel lymph node and micrometastases in breast cancer patients. The traditional histopathological, immunohistochemical, and reverse transcriptase polymerase chain reaction procedures being used for micrometastases detection had serious drawbacks of high false negativity, specificity variations and false positivity of the results. Photon emission fluorescence multiplexing characteristics of the quantum dots make them potentially ideal probes for studying the dynamics of cellular processes over time such as continuous tracking of cell migration, differentiation, and metastases. In breast cancer, QDs based molecular and genomic detections had an unparallel high sensitivity and specificity.
Breast ; Breast Neoplasms ; Cell Movement ; Early Detection of Cancer ; Fluorescence ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Nitriles ; Pyrethrins ; Quantum Dots ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; Track and Field

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Complications of Augmentation Mammaplasty with Autologous Fat Grafts.

Sangdal LEE

Journal of Breast Cancer.2009;12(1):54-59. doi:10.4048/jbc.2009.12.1.54

PURPOSE: Autolougous fat grafting to the breast for cosmetic enlargement remains controversial because the efficacy and the complications due to fat necrosis are unclear. METHODS: Ten cases who underwent autologous fat grafting to the breast for enlargement and visited author's clinic from October 2006 to March 2008 were evaluated retrospectively. Mammography, ultrosonography, culture, cytology, operative findings and results were reviewed for each cases. RESULTS: The study group consisted of 7 cases for additional augmentation mammaplasty, 1 case for breast abscess, 2 cases for breast examination. Two of 7 augmentation cases had multiple palpable masses. One of 2 cases for breast examination had fat grafts 20 months ago and have suffered from painful huge masses especially on exercise. One case with abscess had fat graft 4 months ago and have suffered from painful reddish swelling. On mammography of 9 cases except 1 breast abscess, malignancy could not be excluded in 2 cases because of bizarre forms of multiple microcalcifications. On ultrasonography of 8 cases, there were ill defined hypoechoic masses in 2 cases which needed additional cytology for rule out malignancy. There were implant puncture in all 2 cases with silicone implants, and in case with abscess, there were S. epidermidis in culture. Among 7 augmentation mammaplasty cases, removal of fat necrosis was performed simultaneously in 1 case with severely palpable masses but postoperative seroma formation and capsular contracture occurred. CONCLUSION: Autologous fat grafting for breast augmentation can make masses, abscess and microcalcifications on mammography due to fat necrosis which compromise breast cancer detection. Additional study is necessary to evaluate the efficacy of fat stem cell grafts as an alternative to traditional method.
Abscess ; Breast ; Breast Neoplasms ; Contracture ; Cosmetics ; Fat Necrosis ; Female ; Mammaplasty ; Mammography ; Punctures ; Retrospective Studies ; Seroma ; Silicones ; Stem Cells ; Transplants

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Clinical Analysis of Medullary Carcinoma of the Breast.

Jae Won OH ; Seho PARK ; Joo Hee KIM ; Ja Seung KOO ; Ho HUR ; Woo Ick YANG ; Byeong Woo PARK ; Kyong Sik LEE

Journal of Breast Cancer.2009;12(1):47-53. doi:10.4048/jbc.2009.12.1.47

PURPOSE: Medullary carcinoma of the breast is a variant of breast cancer characterized by the histologic appearance of poorly differentiated cells surrounded by a prominent lymphoid stroma. Medullary carcinoma has been reported to carry a prognosis better than other invasive breast carcinomas, but it is frequently overdiagnosed due to the difficulty in diagnosis. The aim of this study was to assess the clinical manifestations and outcome of medullary carcinoma of the breast. METHODS: We reviewed the data of 91 patients diagnosed with medullary carcinoma and 3,743 patients with invasive ductal carcinoma, not otherwise specified (NOS) from January 1980 to December 2005 at Yonsei University Severance Hospital. The clinicopathologic features, disease free survival (DFS) and overall survival (OS) for patients with medullary carcinoma were compared with those of the NOS patients. RESULTS: With reviewing the pathologic slides, 69 (75.8%) patients had findings compatible with typical medullary carcinoma (TMC) and the remaining 22 (24.2%) patients were reclassified as atypical medullary carcinoma (AMC). Early stage cancer was more frequent at medullary carcinoma and lymph node positive cancer was less frequent at medullary carcinoma. The expression of ER/PR was positive in either the TMC (18.9%/16.2%) and AMC (15.0%/20.0%) as compared to the NOS (63.2%/57.2%), and the difference was significant (p<0.001). In contrast, the HER-2/neu expression rate was significantly higher in the TMC (47.4%) and AMC (45.5%) than in the NOS (28.3%, p=0.001). The 10-year disease free survival and 10-year overall survival of the atypical medullary carcinoma patients (67.8%, 77.8%) were in fact similar to the NOS carcinoma patients (68.3%, 74.7%). There was significant difference in 10-year disease free survival and 10-year overall survival between the TMC (77.8%, 86.0%) and NOS carcinoma (68.3%, 74.7%) patients (p=0.002, p=0.006). CONCLUSION: The clinical outcome of typical medullary carcinoma is favorable in spite of its aggressive pathologic features and it differs from atypical medullary carcinoma. For precise prediction of prognosis of medullary cancer, we should apply strict criteria for the diagnosis of subtype with medullary features.
Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Carcinoma, Medullary ; Disease-Free Survival ; Humans ; Lymph Nodes ; Prognosis

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The Changes of the Histologic and Biologic Markers Induced by Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

Un Jong CHOI ; Kwang Man LEE

Journal of Breast Cancer.2009;12(1):41-46. doi:10.4048/jbc.2009.12.1.41

PURPOSE: Neoadjuvant chemotherapy (NAC) has become the standard treatment for locally advanced breast cancer. The postoperatively adjuvant systemic treatment is based on the status of the histological and biological markers of either the pre-NAC or the post-NAC. There have been several reports that have demonstrated the changes of the histological and biological markers after NAC. The aim of this study is to investigate the effects of NAC on the expression of the histological and biological markers of breast cancer. METHODS: We analyzed the paired pre- and post-NAC tumor specimens from 37 patients with stage IIIA, IIIB or IIIC breast cancer. All the patients received 2 to 6 cycles of anthracycline-containing NAC. Over 6 pieces of pre-NAC tumor specimens were taken by 14 G core needle from multiple sites of a tumor, and the post-NAC specimens were taken at the time of the operation. The histologic grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), c-erbB2, p53, Ki67, CD31 and p-glycoprotein were analyzed in the paired pre- and post-NAC tumor specimens from 37 patients. RESULTS: Twenty five patients (67.6%) revealed significant changes of more than one marker. The markers that showed changes of more than two grades were as follows; histologic grade in 1, ER in 4, PR in 9, c-erbB2 in 4, p53 in 1, Ki67 in 4, CD31 in 9 and pglycoprotein in 5 patients. In 12 patients (32.4%), significant changes were found in the markers that can influence the decision-making for adjuvant treatment (i.e. ER, PR and c-erbB2). The ER/PR status changed from positive to negative in 4 patients and c-erbB2 was changed from positive to negative in 3 patients. Among those patients, the strategy of adjuvant treatment was adjusted according to the changes. CONCLUSION: The specimens for the histologic and biologic markers of a tumor should be taken before NAC because NAC can have an influence on the expression of the prognostic markers of locally advanced breast cancers, and this may subsequently influence predicting the prognosis and making the decision for adjuvant systemic treatment.
Biomarkers ; Breast ; Breast Neoplasms ; Estrogens ; Humans ; Needles ; P-Glycoprotein ; Prognosis ; Receptors, Progesterone

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The Use of a Corrective Procedure with Vicryl Mesh for Oncoplastic Surgery of the Breast.

Tae Ik EOM ; Byung Seup KIM ; Bon Young KOO ; Jong Wan KIM ; Young Ah LIM ; Han Hee LEE ; Su Jung LEE ; Hee Joon KANG ; Lee Su KIM

Journal of Breast Cancer.2009;12(1):36-40. doi:10.4048/jbc.2009.12.1.36

PURPOSE: In addition to the oncological results, cosmetic results are very important to cancer patients. Currently, the use of oncoplastic surgery is an emerging approach. In this study, we examined the clinical outcomes of the use of a corrective procedure with an absorbable implant, a Vicryl mesh(R), as compared with the use of conventional breast conserving surgery (BCS). METHODS: Fifty six patients who completed questionnaire were enrolled in the study. For 33 cases, BCS was performed concurrently with the use of a Vicryl mesh and for the other 23 cases, conventional BCS alone was performed. Contraindications of the use of corrective procedure were a patient age over 60 year, diabetes, neoadjuvant chemotherapy and a previous excisional biopsy performed on the same breast. Patients rated their cosmetic outcomes by use of a four point scale. RESULTS: For one of 34 cases, the Vicryl mesh was removed due to infection and this patient was excluded from the study. Twenty seven of the remaining 33 patients (82%) who underwent the corrective procedure with Vicryl mesh were satisfied with their outcome. For patients that received conventional BCS only ten of 23 patients (43%) were satisfied with their outcome (p=0.05). Patient age, body mass index (BMI) and tumor location did not affect the cosmetic outcomes of the corrective procedure. When the resection area of the breast was 40-70 cm2, 88% of the patients were satisfied with their outcome. CONCLUSION: This study suggested that the use of Vicryl mesh correction was superior to the use of conventional BCS alone for cosmesis. This method appears to provide a satisfactory outcome for oncoplastic surgery of the breast.
Absorbable Implants ; Biopsy ; Body Mass Index ; Breast ; Cosmetics ; Humans ; Mastectomy, Segmental ; Polyglactin 910 ; Surveys and Questionnaires

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Intraparenchymal Methylene Blue Injection for Sentinel Lymph Node in Breast Cancer Patients does not Interfere with the Pulse Oximetry Readings.

Fatih AYDOGAN ; Ziya SALIHOGLU ; Cihan URAS ; Ilhan KARABICAK ; Varol CELIK ; Ali CERCEL ; Semih BAGHAKI ; Ufuk TOPUZ ; Deniz ATASOY ; Rovnat BABAZADE ; Hilal UNAL

Journal of Breast Cancer.2009;12(1):32-35. doi:10.4048/jbc.2009.12.1.32

PURPOSE: Alteration in oxygen saturation is a side effect of the dye used in sentinel lymph node biopsy. The object of this study was to determine the possible effects of methylene blue on the oxygen saturation in patients undergoing sentinel lymph node biopsy. METHODS: The complete peroperative records of 148 patients who underwent sentinel lymph node biopsy with intraparenchymal injection of methylene blue were reviewed. The data reviewed included the preinjection pulse oximeter saturation readings and the postinjection values until the readings returned to the preoperative levels in the postanesthesia care unit. RESULTS: The pulse oximetry values were recorded preoperatively, after intubation and, at 15, 30, 45, and 60 minutes of the operation. The results showed that methylene blue did not cause any significant changes in oxygen saturation levels. CONCLUSION: We suggest that methylene blue might be preferable for the patients with concomitant disease, and for whom close monitoring of their oxygen saturation is required.
Breast ; Breast Neoplasms ; Humans ; Intubation ; Lymph Nodes ; Methylene Blue ; Nitriles ; Oximetry ; Oxygen ; Pyrethrins ; Reading ; Sentinel Lymph Node Biopsy

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Exposure of Surgical Staff to Radiation During Surgical Probe Applications in Breast Cancer.

Recep BEKIS ; Pinar CELIK ; Banu UYSAL ; Mehmet Ali KOCDOR ; Ali SEVINC ; Serdar SAYDAM ; Omer HARMANCIOGLU ; Hatice DURAK

Journal of Breast Cancer.2009;12(1):27-31. doi:10.4048/jbc.2009.12.1.27

PURPOSE: The aim of study was to determine the level of the radiation exposure of surgical staff during surgical probe applications in breast cancer. METHODS: Three operations of a sentinel lymph node biopsy were randomly selected. Spaced circles (50 cm apart) were drawn surrounding the operation bed on the floor. Tc-99m nanocolloid was injected peritumorally and intradermally into a patient. The radiation dose was measured with a GeigerMueller counter placed according to the drawn circles at distances of 50-200 cm from the side of patient's head and bilateral chest while the patient lay on the operation bed. All of the surgical procedures were recorded with a video camera and were monitored. RESULTS: The whole body dose to the senior surgeon was calculated as 2.00-4.70 microSv which means that a senior surgeon can perform 212-500 procedures per year to reach the annual International Commission on Radiological Protection radiation dose limit for a member of the public. CONCLUSION: We concluded that radiation risk to the surgical staff is low from sentinel node detection with the use of radiocolloids.
Breast ; Breast Neoplasms ; Floors and Floorcoverings ; Head ; Humans ; Nitriles ; Organothiophosphorus Compounds ; Pyrethrins ; Sentinel Lymph Node Biopsy ; Thorax

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