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OBJECTIVE: The aim of this study was to present the results of early experience of robot-assisted nipple sparing mastectomy (RANSM). BACKGROUND: RANSM improves cosmetic outcomes over conventional nipple-sparing mastectomy. However, data on the feasibility and safety of the RANSM are limited. METHODS: Patients who underwent RANSM with immediate breast reconstruction as part of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) from November 2016 to January 2020 were enrolled. clinicopathologic characteristics, perioperative complications, and operation time were collected. RESULTS: Overall, 73 women underwent 82 RANSM procedures conducted by 11 breast surgeons at 8 institutions. The median patient age was 45.5âyears old (20-66âyears), and 52 (63.4%) patients were premenopausal. Invasive breast cancer was noted in 55 cases (40 cases were stage i, 11 cases were stage ii, and 4 cases were stage iii, respectively) and ductal carcinoma in-situ was recorded in 20 cases. Of those, 3 patients with BRCA1/2 mutation carriers underwent contralateral risk-reducing RANSM. The median length of hospitalization was 12.0âdays (5.0-24.0âdays). The incision location was the mid-axillary line and the median incision length was 50.0âmm (30.0-60.0âmm). Median total operation time, median total mastectomy time, and median reconstruction time was 307.0 minutes (163.0-796.0 minutes), 189.5 minutes (97.5-325.0 minutes), and 119.5 minutes (45.0-689.0 minutes). Only 2 cases (2.5%) required reoperation. Nipple ischemia was found in 9 cases (10.9%) but only 1 case (1.2%) required nipple excision given that 8 cases (9.7%) resolved spontaneously. Skin ischemia was observed in 5 cases (6.1%) and only 2 (2.4%) cases needed skin excision whereas 3 cases (3.6%) resolved spontaneously. There was no conversion to open surgery orcases of mortality. The mean time for mastectomy among surgeons who performed more than 10 cases was 182.3 minutes (± 53.7, minutes) and 195.4 minutes (± 50.4, minutes). CONCLUSION: This was the first report of RANSM conducted in the KoREa-BSG. RANSM is technically feasible and acceptable with a short learning curve. Further prospective research to evaluate surgical and oncologic outcomes is needed.
Subject(s)
Breast Neoplasms , Mammaplasty , Robotics , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Endoscopy/methods , Female , Humans , Male , Mammaplasty/methods , Mastectomy/methods , Middle Aged , Nipples/surgeryABSTRACT
BACKGROUND: Increasing rates of breast cancer screening have been associated with an increasing frequency of non-palpable breast lesions detection. Preoperative breast lesion localization is essential for optimizing excision accuracy. This study aimed to evaluate the efficacy and safety of indocyanine green (ICG) hyaluronic acid injection as a novel mixture for localization. METHODS: We performed a prospective clinical trial with female patients who underwent surgery for non-palpable breast lesions. All patients were sequentially assigned to the control group (localization with activated charcoal), Test Group 1 (ICG-hyaluronic acid mixture 0.1 mL), or Test Group 2 (ICG-hyaluronic acid mixture 0.2 mL) by 1:1:1 ratio. RESULTS: A total of 44 patients were eligible for this study (Control Group = 14, Test Group 1 = 15, Test Group 2 = 15 patients). Fibroadenoma (n = 17, 38.6%) accounted for the largest proportion of diagnoses, and five patients (11.4%) were diagnosed with malignancies. There were no statistically significant differences in baseline characteristics among the three groups. The marking rate was over 86% in all groups, with no significant intergroup differences. Skin pigmentation was only observed in the control group. The mean accuracy of resection (the greatest diameter of the excised specimen divided by the greatest diameter of the preoperative lesion as observed using ultrasonography, with values closer to 1 reflecting a higher accuracy) was 3.7 in the control group, 2.2 in Test Group 1, and 2.1 in Test Group 2 (p = 0.037 between Controls and Test Group 1, p = 0.744 between Test Group 1 and Test Group 2, and p = 0.026 between Controls and Test Group 2). CONCLUSION: ICG-hyaluronic acid injection is a novel method that was shown to accurately localize non-palpable breast lesions and was associated with no skin pigmentation. Further research is required to apply this method to malignant breast lesions. Trial registration "A Multicenter Open-label, Parallel, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of LuminoMark™ Inj. (Conc. for Fluorescence) Localization in Patients with Non-palpable Breast Lesions" was prospectively registered as a trial (ClinicalTrials. gov Identifier: NCT03743259, date of registration: May 29, 2018, https://clinicaltrials.gov/ct2/show/NCT03743259 ).
Subject(s)
Breast Neoplasms , Hyaluronic Acid , Indocyanine Green , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Female , Humans , Hyaluronic Acid/adverse effects , Hyaluronic Acid/therapeutic use , Indocyanine Green/adverse effects , Indocyanine Green/therapeutic use , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. METHODS: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. DISCUSSION: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Breast Neoplasms/mortality , Disease-Free Survival , Female , Goserelin/administration & dosage , Humans , Kaplan-Meier Estimate , Menstruation , Premenopause , Tamoxifen/administration & dosage , Treatment OutcomeABSTRACT
Acinic cell carcinoma is a rare malignant tumor that accounts for 2%-3% of salivary gland tumors. Acinic cell carcinoma arising from the breast is extremely rare, with only approximately 70 cases reported to date. Owing to its rarity, previous studies have primarily focused on pathological findings. Herein, we present the clinical and radiological features of acinic cell carcinoma of the breast in a 33-year-old woman.
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Importance: While nipple-sparing mastectomy (NSM) for breast cancer was only performed using the open method in the past, its frequency using endoscopic and robotic surgical instruments has been increasing rapidly. However, there are limited studies regarding postoperative complications and the benefits and drawbacks of minimal access NSM (M-NSM) compared with conventional NSM (C-NSM). Objective: To examine the differences in postoperative complications between C-NSM and M-NSM. Design, Setting, Participants: This was a retrospective multicenter cohort study enrolling 1583 female patients aged 19 years and older with breast cancer who underwent NSM at 21 university hospitals in Korea between January 2018 and December 2020. Those with mastectomy without preserving the nipple-areolar complex (NAC), clinical or pathological malignancy in the NAC, inflammatory breast cancer, breast cancer infiltrating the chest wall or skin, metastatic breast cancer, or insufficient medical records were excluded. Data were analyzed from November 2021 to March 2024. Exposures: M-NSM or C-NSM. Main Outcomes and Measures: Clinicopathological factors and postoperative complications within 3 months of surgery were assessed. Statistical analyses, including logistic regression, were used to identify the factors associated with complications. Results: There were 1356 individuals (mean [SD] age, 45.47 [8.56] years) undergoing C-NSM and 227 (mean [SD] age, 45.41 [7.99] years) undergoing M-NSM (35 endoscopy assisted and 192 robot assisted). There was no significant difference between the 2 groups regarding short- and long-term postoperative complications (<30 days: C-NSM, 465 of 1356 [34.29%] vs M-NSM, 73 of 227 [32.16%]; P = .53; <90 days: C-NSM, 525 of 1356 [38.72%] vs M-NSM, 73 of 227 [32.16%]; P = .06). Nipple-areolar complex necrosis was more common in the long term after C-NSM than M-NSM (C-NSM, 91 of 1356 [6.71%] vs M-NSM, 5 of 227 [2.20%]; P = .04). Wound infection occurred more frequently after M-NSM (C-NSM, 58 of 1356 [4.28%] vs M-NSM, 18 of 227 [7.93%]; P = .03). Postoperative seroma occurred more frequently after C-NSM (C-NSM, 193 of 1356 [14.23%] vs M-NSM, 21 of 227 [9.25%]; P = .04). Mild or severe breast ptosis was a significant risk factor for nipple or areolar necrosis (odds ratio [OR], 4.75; 95% CI, 1.66-13.60; P = .004 and OR, 8.78; 95% CI, 1.88-41.02; P = .006, respectively). Conversely, use of a midaxillary, anterior axillary, or axillary incision was associated with a lower risk of necrosis (OR for other incisions, 32.72; 95% CI, 2.11-508.36; P = .01). Necrosis occurred significantly less often in direct-to-implant breast reconstruction compared to other breast reconstructions (OR, 2.85; 95% CI, 1.11-7.34; P = .03). Conclusions and Relevance: The similar complication rates between C-NSM and M-NSM demonstrates that both methods were equally safe, allowing the choice to be guided by patient preferences and specific needs.
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Purpose: The incidence of early tumor detection is increasing due to popularization of breast cancer screening and the development of imaging techniques. Thus, suitable preoperative localization is required for proper diagnosis and treatment of non-palpable breast lesions. The purpose of this study was to evaluate the efficacy and safety of indocyanine green (ICG)-hyaluronic acid (HA) mixture for lesion localization compared to activated charcoal. Methods: This was a multicenter, randomized, open-label, parallel phase 3 clinical trial performed at four centers in Korea. Female patients scheduled for surgery to remove non-palpable breast lesions were enrolled. One hundred and nine patients were randomly assigned to a control group (activated charcoal: 0.3. - 1 mL) or a study group (ICG-HA mixture, 0.2 mL) for the localization of a breast lesion. The primary endpoint was the accuracy of resection. Secondary endpoints included the technical success rate, histopathological accuracy, skin pigmentation rate, and adverse event rate. Results: A total of 104 patients were eligible for per-protocol analysis (control group, n = 51; study group, n = 53). The accuracy of resection in the study group was not inferior to that of the control group (90.57% vs. 98.04%, 95% confidence interval (CI): -2.31 - 18.91, p = 0.21). There was no statistically significant difference in technical success rate between the two groups (marking on breast skin: p = 0.11, marking on the excised specimen: p = 0.12). However, there were statistically significant differences in histopathological accuracy (0.26 ± 0.13 vs. 0.33 ± 0.17, p = 0.01) and skin pigmentation rate (0.00% vs. 30.77%, p< 0.01). Adverse events were not reported in either group. Conclusions: When localization was performed using ICG-HA, the accuracy of resection was not inferior to that of activated charcoal. However, skin pigmentation rate was significantly lower. In conclusion, ICG-HA is effective and safe for localizing of non-palpable breast lesions.
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PURPOSE: Pegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. MATERIALS AND METHODS: This was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. RESULTS: Pegfilgrastim administration reduced FN by 11.8-1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. CONCLUSION: The use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.
Subject(s)
Breast Neoplasms , Febrile Neutropenia , Humans , Female , Breast Neoplasms/drug therapy , Incidence , Prospective Studies , Febrile Neutropenia/chemically induced , Febrile Neutropenia/epidemiology , Febrile Neutropenia/prevention & control , Pain , Republic of Korea/epidemiologyABSTRACT
PURPOSE: Restricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer. This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND. METHODS: We designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period). RESULTS: A total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (-30.04 ± 27.76 vs. -42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (-3.92 ± 9.80 vs. -10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group. CONCLUSION: We suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967146.
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PURPOSE: To investigate the factors affecting detectability of invasive breast cancers on BSGI. MATERIAL AND METHODS: We evaluated BSGI, mammography and pathologic reports of 89 patients with invasive breast cancers. RESULTS: 87.6% were visible on BSGI. Cancer in old or postmenopausal women were more visible on BSGI (pâ¯=â¯0.003, 0.046). Cancersâ¯≥â¯1.0â¯cm in size were significantly more visible on BSGI than those <1â¯cm in size (pâ¯=â¯0.002). Cancers in fatty breasts were more visible than those in dense breasts (pâ¯=â¯0.042). CONCLUSION: Invasive cancers in older, postmenopausal patients, cancers with size ≥1.0â¯cm, and those with fatty breast are better visualized by BSGI, than those in younger, premenopausal patients, with size <1.0â¯cm and dense breast.
Subject(s)
Breast Neoplasms/pathology , Breast/pathology , Gamma Rays , Mammography/methods , Radionuclide Imaging/methods , Adipose Tissue , Adult , Age Factors , Aged , Aged, 80 and over , Breast/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Female , Humans , Middle Aged , Retrospective StudiesABSTRACT
Little is known about the natural history of right colonic diverticulitis treated with conservative management. The purpose of this study was to analyze the short-term outcome of a conservative approach to the treatment of patients with acute right colonic diverticulitis. A retrospective review of the clinical and radiological findings of 62 patients with acute right colonic diverticulitis was carried out. Conservative treatment was provided to 47 patients and surgical treatment to 15 patients with the diagnosis of acute right colonic diverticulitis. An initial ultrasound was performed in 45 of 62 patients (73%) and a CT was performed in 16 of 62 patients (26%). Diverticulitis was confirmed pretreatment diagnosis in 56 of 61 (91.8%) patients who had radiological evaluation. There were seven (11.3%) pericolic abscesses identified as a complication of the diverticulitis. All 47 patients who received conservative management were successfully treated and had improvement of symptoms with no sign of clinical deterioration. For the fifteen patients who had surgery: 5 had right hemicolectomies, 8 had appendectomies without diverticulectomy, 1 had an appendectomy with diverticulectomy, and 1 had diverticulectomy alone. During a median followup of 23.9 months, two of 55 (3.6%) patients who did not have surgical resection for inflamed diverticulum had recurrences one and ten months after the initial treatment; they were successfully treated again with bowel rest and antibiotics without complication. Conservative treatment should be considered as a safe and effective option for acute right colonic diverticulitis. In addition, a less aggressive approach may be more suitable for recurrent diverticulitis than extended surgical resection.
Subject(s)
Diverticulitis, Colonic/therapy , Acute Disease , Adult , Digestive System Surgical Procedures , Diverticulitis, Colonic/complications , Diverticulitis, Colonic/diagnosis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Two consecutive surveys for breast surgeons in Korea were conducted to comprehend the practice patterns and perceptions on margin status after breast-conserving surgery. The surveys were conducted online in 2014 (initial) and 2016 (follow-up). A total of 126 and 88 responses were obtained in the initial and follow-up survey, respectively. More than 80% of the respondents replied to routinely apply frozen section biopsy for intraoperative margin assessment in both surveys. Re-excision recommendations of the margin for invasive cancer significantly changed from a close margin to a positive margin over time (p=0.033). Most of the respondents (73.8%) defined a negative margin as "no ink on tumor" in invasive cancer, whereas more diverse responses were observed in ductal carcinoma in situ cases. The influence of guideline establishment for negative margins has been identified. A high uptake rate of intraoperative frozen section biopsy was noted and routine use needs reconsideration.
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BACKGROUND: Neogenin is expressed in cap cells that have been suggested to be mammary stem or precursor cells. Neogenin is known to play an important role in mammary morphogenesis; however its relationship to tumorigenesis remains to be elucidated. METHODS: To compare the expression levels of neogenin in cells with different tumorigenicity, the expression levels in M13SV1, M13SV1R2 and M13SV1R2N1 cells, which are immortalized derivatives of type I human breast epithelial cells, were evaluated. Then we measured the expression level of neogenin in paired normal and cancer tissues from eight breast cancer patients. Tissue array analysis was performed for 54 human breast tissue samples with different histology, and the results were divided into four categories (none, weak, moderate, strong) by a single well-trained blinded pathologist and statistically analyzed. RESULTS: The nontumorigenic M13SV1 cells and normal tissues showed stronger expression of neogenin than the M13SV1R2N1 cells and the paired cancer tissues. In the tissue array, all (8/8) of the normal breast tissues showed strong neogenin expression, while 93.5% (43/46) of breast cancer tissues had either no expression or only moderate levels of neogenin expression. There was a significant difference, in the expression level of neogenin, in comparisons between normal and infiltrating ductal carcinoma (p < 0.001). CONCLUSION: Neogenin may play a role in mammary carcinogenesis as well as morphogenesis, and the expression may be inversely correlated with mammary carcinogenicity. The value of neogenin as a potential prognostic factor needs further evaluation.
Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast/metabolism , Gene Expression Regulation, Neoplastic , Membrane Proteins/biosynthesis , Biomarkers, Tumor/biosynthesis , Blotting, Western , Breast/pathology , Cell Line , Cell Line, Tumor , Epithelial Cells/metabolism , Humans , Immunohistochemistry , Models, Statistical , Neoplasm Metastasis , Prognosis , Tissue DistributionABSTRACT
BACKGROUND: VEGF (Vascular Endothelial Growth Factor) is a key factor of angiogenesis and high tissue VEGF levels are related to a poor prognosis in breast cancer. MATERIALS AND METHODS: By semi-quantitative RT-PCR, we determined the relative expressions of VEGF mRNA in MCF-7 (both ER-alpha+ and ER-beta+ (mainly ER-alpha+), PR+, bcl-2+, EGFR-) and MB-MDA-231 (only ER-beta+, PR-, EGFR-) breast cancer cells which were treated with estrogen, tamoxifen and EGF (Epidermal Growth Factor). RESULTS: In MCF-7 cell lines, estrogen induced the expression of VEGF mRNA while tamoxifen reduced its expression. Estrogen and tamoxifen did not confer any significant effect on MB-MDA-231 cells and EGF showed no significant effect on MCF-7 or MB-MDA-231. CONCLUSION: Reduced VEGF mRNA expression of MCF-7 cells treated with tamoxifen may be related to the antagonistic effect of tamoxifen on ER-positive breast cancer, and this antagonistic effect may be related to ER-alpha.
Subject(s)
Breast Neoplasms/metabolism , Epidermal Growth Factor/pharmacology , Estradiol/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Tamoxifen/pharmacology , Transcription, Genetic/drug effects , Vascular Endothelial Growth Factor A/biosynthesis , Breast Neoplasms/genetics , Cell Line, Tumor , Densitometry , Humans , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Vascular Endothelial Growth Factor A/geneticsABSTRACT
PURPOSE: To investigate the therapeutic effectiveness of ultrasound (US)-guided trigger point injection for myofascial trigger points (MTrPs) in the internal rotator muscles of the shoulder in post-mastectomy patients. MATERIALS AND METHODS: This pilot study was a non-controlled, prospective, clinical trial. Nineteen post-mastectomy patients with a diagnosis of at least one active MTrP in the subscapularis and/or pectoralis muscles were included. We performed trigger point injections into the subscapularis muscle deep behind the scapula as well as the pectoralis muscle for diagnostic and therapeutic purpose by the newly developed US-guided method. RESULTS: Visual analogue scale and range of motion of the shoulder for external rotation and of abduction showed significant improvement immediately after the first injection and 3 months after the last injection compared with baseline (p<0.05 for both). Duration from onset to surgery and duration of myofascial pain syndrome in the good responder group were significantly shorter than in the bad responder group (p<0.05). Patients did not report any complications related to the procedure or serious adverse events attributable to the treatment. CONCLUSION: In post-mastectomy patients with shoulder pain, US-guided trigger point injections of the subscapularis and/or pectoralis muscles are effective for both diagnosis and treatment when the cause of shoulder pain is suspected to originate from active MTrPs in these muscles, particularly, the subscapularis.
Subject(s)
Pectoralis Muscles/diagnostic imaging , Trigger Points/diagnostic imaging , Adult , Aged , Anesthetics, Local/administration & dosage , Anesthetics, Local/therapeutic use , Female , Humans , Injections, Intramuscular/methods , Lidocaine/administration & dosage , Lidocaine/therapeutic use , Mastectomy , Middle Aged , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/drug effects , Myofascial Pain Syndromes/drug therapy , Pectoralis Muscles/drug effects , UltrasonographyABSTRACT
The RUNX3 gene is regarded as a tumor suppressor gene in many human solid tumors, and its inactivation is believed to be related with solid tumor carcinogenesis. As little information is available about the role of the RUNX3 gene in breast cancer, we investigated the relationship between the RUNX3 gene and breast cancer. We performed reverse transcriptase-polymerases chain reaction (RT-PCR), methylation specific PCR, and bicolor fluorescent in situ hybridization analysis in an effort to reveal related mechanisms. Forty breast tissue samples and 13 cell lines were used in this study. Eighty-five percent of breast cancer tissues showed downregulated RUNX3 gene expression, whereas it was downregulated in only 25% of normal breast tissues by RT-PCR assay. Sixty-seven percent of breast cancer cell lines showed downregulated RUNX3 expression, but the RUNX3 gene was not expressed in two normal breast cell lines. Hypermethylation was observed in 53% of breast cancer tissues and 57% of breast cancer cell lines. Hemizygous deletion was observed in 43% of breast cancer cell lines. Hypermethylation and/or hemizygous deletion was observed in 5 of 7 breast cancer cell lines, and the four of these five examined showed no RUNX3 gene expression. We suggest that various mechanisms, including methylation and hemizygous deletion, could contribute to RUNX3 gene inactivation.
Subject(s)
Breast Neoplasms/genetics , Carcinoma, Ductal, Breast/genetics , Core Binding Factor Alpha 3 Subunit/genetics , Base Sequence , Case-Control Studies , Cell Line, Tumor , DNA Methylation , DNA, Neoplasm/genetics , Down-Regulation , Female , Gene Deletion , Humans , In Situ Hybridization, Fluorescence , Promoter Regions, Genetic , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND: Using the new 2003 American Joint Committee on Cancer (AJCC) staging system, the authors evaluated the usefulness of the staging bone scan in patients with primary breast carcinoma. METHODS: The authors examined 1939 patients with primary breast carcinoma for staging bone scan who were treated at a single institution. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging systems. RESULTS: Bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.7% (5 of 699) for patients with Stage IIA disease, 2.1% (10 of 479) for patients with Stage IIB disease, 4.5% (7 of 154) for patients with Stage IIIA disease, and 10.5% (2 of 19) for patients with Stage IIIB disease according to the 1988 AJCC staging system. The authors found a significant difference in the bone metastasis rate between patients with Stages IIA and IIB disease in the 1988 staging system (P = 0.039). Reevaluating the patients by the 2003 system resulted in significant upstaging, especially for patients with Stage II/III disease. According to the 2003 staging system, bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.6% (4 of 648) for patients with Stage IIA disease, 0.6% (2 of 310) for patients with Stage IIB disease, 4.0% (9 of 225) for patients with Stage IIIA disease, 16.7% (2 of 12) for patients with Stage IIIB disease, and 4.4% (7 of 158) for patients with Stage IIIC disease. It was noteworthy that there was a significant difference between Stages IIB and IIIA in the 2003 staging system (P = 0.010). CONCLUSIONS: Stage reclassification using the new AJCC staging system resulted in upstaging of high-risk patients, as well as a significant decrease in the bone metastasis rate in patients with Stage IIB breast carcinoma. Considering the cost-effectiveness of staging bone scan, the data suggested that it was of little value for patients with Stage I and II breast carcinoma, but was highly recommended for patients with worse than Stage III disease by the new 2003 staging system.
Subject(s)
Bone Neoplasms/diagnostic imaging , Bone and Bones/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Neoplasm Staging/standards , Adult , Aged , Aged, 80 and over , Bone Neoplasms/secondary , Breast Neoplasms/therapy , Female , Humans , Middle Aged , Neoplasm Invasiveness/pathology , Predictive Value of Tests , Prospective Studies , Radionuclide Imaging , Radiopharmaceuticals , Risk Factors , Survival RateABSTRACT
Phospholipase C-gamma1 (PLCgamma1) plays a critical role in cell growth and proliferation by generating the second messengers, diacylglycerol and 1, 4, 5-inositol triphosphate. To investigate the roles of Src homology domain 2 and domain 3 of PLCgamma1 in PLCgamma1-mediated cell signaling, we characterized some proteins binding to these domains in the MCF7 and MDA-MB-231 breast cancer cell lines. Of the several proteins that bind to glutathione-S-transferase-SH2/SH2/SH3, we identified an 85 kDa protein that binds to the SH3 domain of PLCgamma1 as the guanine nucleotide exchange factor, p21-activated protein kinase-interacting exchange factor-a (betaPix-a). BetaPix-a co-immunoprecipitated with PLCgamma1 in breast cancer tissues extracts and in MCF7 and MDA-MB-231 cell extracts. In addition, PDGF-stimulated PLCgamma1 activity was elevated in betaPix-a-overexpressing NIH3T3 cells. Our results suggest that betaPix-a binds to the Src homology domain 3 of PLCgamma1 and promotes tumor growth in breast cancer by enhancing the activity PLCgamma1.