The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress.

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.

The distance between breast cancer and the skin is associated with axillary nodal metastasis.

BACKGROUND AND OBJECTIVES: More superficially located tumors may be more likely than deeper tumors to metastasize to the axillary nodes via the lymphatics. The aim of this study was to determine whether breast cancer distance from the skin affects axillary node metastasis, ipsilateral breast cancer recurrence, or recurrence-free survival. MATERIALS AND METHODS: A total of 1,005 consecutive patients with breast cancer who underwent surgery between January 2003 and December 2009 were selected. The distance of the tumor from the skin was measured from the skin to the most anterior hypoechoic leading edge of the lesion. RESULTS: In total, 603 (68%) patients had no axillary nodal metastasis, and 288 (32%) had axillary nodal metastasis. A breast cancer distance from the skin <3 mm induced more axillary nodal metastasis (P = 0.039). However, no significant correlation was observed between breast cancer distance from the skin <3 mm and ipsilateral breast cancer recurrence (P = 0.788) or recurrence-free survival (P = 0.353). CONCLUSIONS: Breast cancers located closer to the skin had a higher incidence of axillary nodal metastasis. Therefore, tumor distance from the skin should be considered when evaluating a patient with breast cancer and considering the risk of nodal metastasis.

Does papillary thyroid carcinoma have a better prognosis with or without Hashimoto thyroiditis?

BACKGROUND: It has been reported that the BRAF (V600E) mutation is related to a low frequency of background Hashimoto thyroiditis (HT); however, there are not many factors known to be related to the development of HT. The aim of this study was to determine whether patients with both papillary thyroid carcinoma (PTC) and HT show aggressive features, by investigating the clinicopathological features of HT in patients with PTC. METHODS: A database of patients with PTC who underwent thyroidectomy between October 2008 and August 2012 was collected and reviewed. All 2464 patients were offered a thyroidectomy, and DNA was extracted from the atypical cells in the surgical specimens for detection of the BRAF (V600E) mutation. Clinical and pathological characteristics were also investigated. RESULTS: Four hundred and fifty-two of 1945 (23.2%) patients were diagnosed with HT, and of these, 119 (72.1%) had a BRAF (V600E) mutation. HT was not significantly associated with the BRAF (V600E) mutation (P < 0.001) and extrathyroidal extensions (P = 0.005) but was associated with a low stage (P = 0.011) and female predominance (P < 0.001). In a subgroup analysis for gender, HT was associated with a low probability of BRAF (V600E) mutations in both genders (P < 0.001 for both females and males). Also, recurrence was significantly associated with HT (OR 0.297, CI 0.099-0.890, P = 0.030), lymph node ratio (OR 2.545, CI 1.092-5.931, P = 0.030), and BRAF (V600E) mutation (OR 2.075, CI 1.021-4.217, P = 0.044). However, there was no relationship with clinicopathological factors or with death. CONCLUSIONS: Our results show that HT in patients with PTC is associated with a low probability of BRAF (V600E) mutations. Moreover, HT was correlated with some factors that were associated with less aggressive clinical features and inversely related to recurrence. Therefore, these results may be useful to predict whether PTC concurrent with HT exhibits a better prognosis than PTC alone.

Correlation between obesity and clinicopathological factors in patients with papillary thyroid cancer.

PURPOSE: Epidemiological studies have shown that obesity is associated with an increased risk of thyroid cancer. However, the exact nature of the relationship, especially with respect to the behavior of the cancer, remains uncertain. The objective of this study was to evaluate the correlation between the body mass index (BMI) and clinicopathological features of thyroid cancer patients. METHODS: From January 2009 to April 2010, 716 consecutive patients (602 females and 114 males; mean age 47.02 ± 11.73 years) with papillary thyroid cancer (PTC) were analyzed retrospectively. Patients were divided into two subgroups according to age (<45 years, ≥45 years). The BMI groupings were based on standardized categories set by the World Health Organization. The relationships between the BMI and these parameters were assessed. RESULTS: A non-overweight BMI was associated with a younger age and female gender. Tumor multiplicity was related to a higher BMI. In an age-related subgroup analysis, a higher BMI was correlated with more lymph node involvement (p = 0.004), lymphatic invasion (p = 0.003) and tumor multiplicity (p = 0.008) in patients ≥45 years of age. The absence of an association between the BMI and T stage, nodal status, vascular invasion, lymphatic invasion, and extrathyroidal extension was noted in a statistical analysis. In the subgroup of patients <45 years of age, no positive associations were observed between the BMI and any parameters other than age and sex. CONCLUSIONS: In PTC patients ≥45 years of age, a higher BMI was associated with more aggressive tumor features, such as lymph node metastasis, lymphatic invasion, and tumor multiplicity.

Effect of axillary lymph node dissection after sentinel lymph node biopsy on overall survival in patients with T1 or T2 node-positive breast cancer: report from the Korean Breast Cancer Society.

BACKGROUND: The effect of axillary lymph node dissection (ALND) after sentinel lymph node biopsy (SLNB) in patients with clinically node-negative patients in preoperative evaluations on overall survival (OS) is uncertain. The study aimed to evaluate the difference of survival between node-positive patients who underwent SLNB alone and those who received ALND after SLNB using the Korean Breast Cancer Society registry. METHODS: We enrolled 2,581 patients who met the eligibility criteria. All enrolled patients had T1 or T2 breast cancer, and received mastectomy or breast-conserving treatment followed by documented adjuvant systemic therapy. RESULTS: There were 197 patients with SLNB alone and 2,384 patients with ALND after SLNB. Smaller tumor size, lower number of nodal metastasis, and higher proportion of breast-conserving surgery were found in patients with SLNB alone than in those with ALND after SLNB. There was no significant difference in OS between the two groups by the log-rank test. ALND after SLNB showed no significant improvement in OS in multivariate analysis. CONCLUSIONS: ALND in patients with sentinel metastasis who have T1 or T2 breast cancer receiving adjuvant systemic therapy may not have improved OS.

Comparison of surgical outcomes between papillary thyroid cancer patients treated with the Harmonic ACE scalpel and LigaSure Precise instrument during conventional thyroidectomy: a single-blind prospective randomized controlled trial.

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of thyroidectomy using the Harmonic ACE scalpel (HS) or the LigaSure Precise (LS) instrument in conventional thyroidectomy. MATERIALS AND METHODS: A prospective, randomized controlled trial was performed. Between August 2011 and June 2012, 832 patients who required thyroidectomy for papillary thyroid cancer were randomized into groups treated with either the HS or the LS instrument. Operative time and surgical morbidities were analyzed. RESULTS: A total of 320 patients (HS group, N = 164; LS instrument group, N = 156) were randomized for analysis according to the intention-to-treat principle. There were no statistically significant differences in the operative times (HS group versus LS instrument group: 71.93 ± 18.26 versus 75.15 ± 20.13; P = 0.423), postoperative transient hypoparathyroidism (13.4% versus 14.1%; P = 0.858), and permanent recurrent laryngeal nerve injuries between the two groups. CONCLUSIONS: In this study, both hemostatic devices were safe and effective in terms of postoperative results and complications without any differences.

Expression of receptor activator of nuclear factor kappa-B as a poor prognostic marker in breast cancer.

PURPOSE: Receptor activator of nuclear factor kappa-B and its ligand (RANK/RANKL) and Osteoprotegerin (OPG) are key molecules for regulating osteoclastic activity in bone. However, little is known about the role of RANK-related molecules in breast cancer prognosis. We aimed to evaluate RANK, RANKL, and OPG expression and the associated clinical impact in breast cancer. METHODS: Tissue microarray (TMA) from 185 patients with primary breast cancer was established. Immunohistochemistry for RANK, RANKL, and OPG was performed. Clinicopathologic features and survival outcomes associated with expression of RANK, RANKL, and OPG were analyzed. RESULTS: RANK, RANKL, and OPG were expressed in 74.1%, 78.4%, and 45.9% of patients, respectively. RANKL expression was associated with lower Ki-67 level. OPG expression was related to small tumor size, node negativity, and low Ki-67. There was no significant difference in clinicopathologic features between tumors with RANK and those without RANK. RANK expression was significantly associated with poor disease-free survival in univariate analysis (P = 0.04) and multivariate analysis (P = 0.02). RANKL expression was associated with improved skeletal disease-free survival in multivariate analysis (P = 0.03). CONCLUSIONS: The RANK/RANKL pathway regulated by OPG may have a role in predicting progression and prognosis of breast cancer.

Clinicopathologic characteristics and surgical outcomes of elderly patients with thyroid cancer.

OBJECTIVE: Age is one of the important prognostic factors in thyroid cancer, and old age is generally related to higher rate of post-operative morbidity and mortality. The study analyzed the characteristics of thyroid cancer in elderly patients compared with those in younger patients. METHODS: Patients who underwent surgery between 1992 and 2011 were enrolled. The patients were divided into those ≥70 years of age (older group) and <70 years of age (younger group). Data including clinicopathological features and post-operative complications was analyzed. Molecular markers including Galectin-3, Cyclooxygenase-2, bcl-2, Cyclin D1, Epidermal growth factor receptor and BRAF mutation were reviewed. Survival analyses including recurrence-free survival and overall survival were examined. RESULTS: Of 1867 patients, 98 were age-classified in older group and the remaining 1769 were in younger group. Older group displayed larger tumor size, and increased extrathyroidal extension, vascular invasion and neural invasion than younger group, and all were statistically significant. Molecular marker analyses revealed no significant differences between the groups. Post-operative complication rates were not significantly different between the older and younger groups in both univariate and multivariate analyses. Elderly patients showed poor recurrence-free survival and overall survival than younger patients in univariate analyses. However, age ≥70 years was not associated with poor recurrence-free survival after adjustment of confounding factors. CONCLUSION: Molecular features of elderly patients may be similar with younger patients. Even though aggravated clinicopathological features of thyroid carcinoma are more prevalent in elderly patients, thyroid surgery in elderly patients can be performed with favorable surgical and oncological outcomes.

Breast cancer after kidney transplantation: a single institution review.

BACKGROUND: Improvements in immunosuppression have resulted in long life expectancy of kidney transplants. Unfortunately, the incidence of post-transplant malignancy (PTM) is increasing. The aim of this study was to evaluate the nature and stage-specific prognosis of post-transplant breast cancer (PTBC) compared with breast cancer in the general population, and to suggest optimal treatment strategies. METHODS: A database of 2,139 consecutive kidney transplant patients was reviewed;11 of the patients developed breast cancer. These 11 PTBC cases underwent operations between 1999 and 2011. Next, 2,554 breast cancer patients treated in the same period were reviewed. Kaplan-Meier curves and the log-rank test were used to assess stage-specific survival of breast cancer in our hospital. RESULTS: In total, 142 cases experienced post-transplant malignancy (PTM; 6.6%) and 11 (0.5%) developed PTBC. No one required an adjusted dose of immunosuppressive agent. Two stage III patients died. For all breast cancer patients, 5-year survival by stage was 97.7% for stage I, 92.9% for stage II, 78.6% for stage III, and 49.9% for stage IV. The 5-year survival for expected stage III-specific survival was 66.7% and no significant statistical difference was seen compared to that of the total breast cancer patients (P = 0.213). CONCLUSIONS: The prognosis of PTBC was comparable to that of the general population. These results suggest that the use of immunosuppressants per se does not adversely affect breast cancer.

Feasibility of sentinel lymph node biopsy in breast cancer patients clinically suspected of axillary lymph node metastasis on preoperative imaging.

BACKGROUND: Generally, sentinel lymph node biopsy (SLNB) is performed in patients with clinically negative axillary lymph node (LN). This study was to assess imaging techniques in axillary LN staging and to evaluate the feasibility of SLNB in patients clinically suspected of axillary LN metastasis on preoperative imaging techniques (SI). METHODS: A prospectively maintained database of 767 breast cancer patients enrolled between January 2006 and December 2009 was reviewed. All patients were offered preoperative breast ultrasound, magnetic resonance imaging, and positron emission tomography scanning. SI patients were regarded as those for whom preoperative imaging was "suspicious for axillary LN metastasis" and NSI as "non-suspicious for axillary LN metastasis" on preoperative imaging techniques. Patients were subgrouped by presence of SI and types of axillary operation, and analyzed. RESULTS: For 323 patients who received SLNB, there was no statistically significant difference in axillary recurrence (P=0.119) between SI and NSI groups. There also was no significant difference in axillary recurrence between SLNB and axillary lymph node dissection (ALND) groups in 356 SI patients (P=0.420). The presence of axillary LN metastasis on preoperative imaging carried 82.1% sensitivity and 45.9% specificity for determining axillary LN metastasis on the final pathology. CONCLUSIONS: SLNB in SI patents is safe and feasible. Complications might be avoided by not performing ALND. Therefore, we recommend SLNB, instead of a direct ALND, even in SI patients, for interpreting the exact nodal status and avoiding unnecessary morbidity by performing ALND.

Notch1 receptor as a marker of lymph node metastases in papillary thyroid cancer.

Notch functions as an oncogene or tumor suppressor according to the type of malignancy, and the BRAF(V600E) mutation is commonly observed in thyroid cancer. However, the role of Notch and BRAF(V600E) in papillary thyroid cancer (PTC) is unclear. This study sought to elucidate the clinicopathological characteristics in patients with PTC regarding the expression of Notch1/Notch3 receptors and BRAF(V600E) mutation. Clinicopathological characteristics were evaluated according to the Notch1/Notch3 receptors and BRAF(V600E) mutation in 187 patients with PTC who underwent definitive surgery. Expression of the Notch1 receptor was significantly associated with poor prognostic markers including large tumor size, nodal metastasis, capsular invasion, and extrathyroidal extension. However, there was no significant association between the clinicopathological characteristics and Notch3 receptor expression/BRAF(V600E) mutation. In multivariate analysis, Notch1 receptor expression showed a significant relationship with lymph node metastasis (P = 0.04). Notch1 receptor may be a predictor of lymph node metastasis and may be related to poor prognostic markers in patients with PTC. Further investigation of Notch1 receptor may further the understanding of the pathogenesis of nodal metastasis in PTC.

Comparison of surgical outcomes between endoscopic and robotic thyroidectomy.

OBJECTIVES: Gasless transaxillary endoscopic thyroidectomy offers a distinct advantage over the conventional open operation because it leaves no visible neck scar. Indications have expanded with the development of new surgical techniques and instruments. However, because of the two-dimensional view and the nonflexible instruments, this procedure is not easily amenable for total thyroidectomy. So, robotic surgery has been introduced and offers improved visualization and dexterity. But, it remains unclear whether robotic thyroidectomy offers any potential benefits over endoscopic thyroidectomy. The aim of this present study was to determine whether robotic surgery is superior to endoscopic surgery through a comparison of surgical outcomes. METHODS: Between May 2009 and February 2011, 165 patients underwent endoscopic thyroidectomy (endoscopy group) and 46 patients underwent robotic thyroidectomy (robot group). A gasless transaxillary approach was used in both groups. The two groups were compared in terms of patient characteristics, perioperative clinical results, pathologic findings, and postoperative complication. RESULTS: Both patient groups were similar in terms of patient characteristics, mean number of retrieved central lymph nodes, pathological features, length of hospital stays, postoperative complication rate, and serum Tg level. However, the mean total operation time for thyroidectomy was 126.2 ± 37.84 min in the endoscopy group and 179.6 ± 44.34 min in the robot group (P < 0.001). Postoperative total drainage for lobectomy was 153.3 ± 45.64 for the endoscopy group and 179.9 ± 49.15 for the robot group (P = 0.031). Cost effectiveness is also an important consideration when evidence for predominance of two surgical techniques is lacking. The mean cost of robotic thyroidectomy was $6,655, compared with $829 for endoscopic thyroidectomy (P < 0.001). There was no significant difference in postoperative complications as hypocalcemia, recurrent laryngeal nerve injury, chyle leakage and tracheal injury in the two groups (P = 0.332). CONCLUSION: Robotic thyroidectomy was lengthier in duration than endoscopic thyroidectomy, more costly, and associated with increased postoperative drainage with no improvement in oncologic outcomes or complication rates. Therefore our data do not support any advantage of robotic surgery over endoscopic surgery.

Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer.

BACKGROUND: Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. METHODS: In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR), and human epithelial receptor-2 (HER2) were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC) according to ER, PR, and HER2 status. RESULTS: Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. CONCLUSIONS: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

Present condition analysis of physician assistant in Korea.

This study intended to identify the need for the legalization and development of a systematic program for physician assistants (PAs) by understanding the actual state of PA operation in hospitals. In 114 hospitals assigned as resident training hospitals for surgery, a survey was conducted on the personnel working as PAs in those hospitals; the survey included general personal information, working conditions, training time, and satisfaction. A total of 192 PAs in surgery at 35 hospitals responded to the survey. The types of PAs are Surgical Assistant, Clinical Physician Assistant, Wound Ostomy Care Nurse, Coordinator, and Clinical Research Coordinator. Types of work PAs preformed are surgical assistance, wound dressing, educating patients, overlooking consultation, doing paper works, writing operation records, and confirming examination results which were ordered. The satisfaction level for the position which PAs hold were 29.1% and and satisfaction level which doctors see towards PA was 15%. The role and the job descriptions of PAs are not clear cut, there are many discrepancies among hospitals we studied. As a result, legalization and the implementation of standardized role of PAs will lead to increase level of satisfactions in the work force and the quality of work which PAs perform will be greater.

Lymph node ratio and pN staging in patients with node-positive breast cancer: a report from the Korean breast cancer society.

Patients with node-positive breast cancer are currently classified according to pN stage. Lymph node ratio (LNR), the ratio of positive to total removed lymph nodes, maybe a more useful prognostic factor in these patients. We therefore compared LNR and pN staging as prognostic factors in patients with node-positive breast cancer. Using two large prospective databases of the Korean Breast Cancer Registry (KBCR) and the Asan Medical Center (AMC) Breast Cancer Center of patients with LN-positive breast cancer from 1988 to 2005, we compared the ability of LNR and pN stage to predict patient survival by Cox regression analysis in the overall patient cohort and in subgroups categorized by age and intrinsic subtype. Patients were categorized into low- (≤ 0.20), intermediate- (>0.20 and ≤ 0.65), and high-risk (>0.65) LNR groups. The difference in mortality risk was greater among LNR groups than among patients staged pN1, pN2, and pN3, as assessed by disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. In contrast to LNR risk categories, the survival curves for pN1 and pN2 stage patients overlapped in those aged <35 years and those with her2/neu-enriched or triple-negative tumors. These findings were validated by analyzing a nationwide registry of 15,488 node-positive patients, which showed that patients with pN1 and intermediate LNR risk had poorer DFS (HR 1.7, 95% CI 1.4-2.2) and CSS (HR 1.6, 95% CI 1.1-2.2) than patients with pN2 and low LNR risk. LNR is a better predictor of prognosis than pN stage in women with breast cancer, especially in high-risk patients, including younger women and women with her2/neu-enriched or triple-negative tumors. Treatment decisions should be based on LNR rather than on pN stage.

Expression of nuclear receptor DAX-1 and androgen receptor in human breast cancer.

BACKGROUND: The functions of nuclear receptor DAX-1 and androgen receptor (AR) in breast cancer are unknown and have not been well-characterized in terms of their importance as a predictive or a prognostic factor. The study investigated the relationship between expression of AR, DAX-1, and clinicopathological factors in primary breast cancer patients. METHODS: The data of 476 breast cancer patients who were treated at Seoul St. Mary's hospital from January 2004 to March 2006 were reviewed. Among them, 169 cases (35.5%) were consecutively evaluated for AR and DAX-1 expression. RESULTS: DAX-1 expression was associated with smaller tumor size; earlier disease stage; and higher expression of estrogen receptor (ER), progesterone receptor (PgR) and AR. AR was significantly expressed in patients with smaller tumor size and higher expression of ER, PgR, and DAX-1. In the subgroup analysis of triple negative breast cancer patients, the expression rate of DAX-1 (4/12, 33.3%) was higher than AR (1/12, 8.3%). CONCLUSIONS: The present review revealed a very high expression rate of DAX-1 in human breast cancer (74%). DAX-1 might modify steroidogenic hormone systems like as AR, estrogen receptor, and progesterone receptor. DAX-1 might be a more effective target than AR for triple negative breast cancer.

Role of sonographic elastography in the differential diagnosis of axillary lymph nodes in breast cancer.

OBJECTIVES: The purpose of this study was to evaluate the diagnostic utility of sonographic elastography in differentiating reactive and metastatic axillary lymph nodes in breast cancer. METHODS: A total of 64 lymph nodes (reactive, n = 33; metastatic, n = 31) from 62 patients with breast cancer were examined by both B-mode sonography and elastography from April to July 2009. Two experienced radiologists retrospectively assessed B-mode sonograms by the sum of scores for 4 criteria: short diameter, shape, hilum, and cortical thickening. Elastographic images were given scores of 1 to 4 according to the percentage of high-elasticity areas in the lymph nodes. We compared the diagnostic performance of B-mode sonography, elastography, and combined examinations. We also calculated the strain ratio of the lymph node and subcutaneous fat tissue. RESULTS: The elasticity score for malignant lymph nodes (mean, 3.1) was higher than the score for benign lymph nodes (mean, 2.2; P < .0001). With a cutoff between elasticity scores of 2 and 3, elastography showed 80.7% sensitivity, 66.7% specificity, and 73.4% accuracy. With a cutoff between B-mode sonographic scores of 1 and 2, B-mode sonography showed 74.2% sensitivity and 78.8% specificity. Combined B-mode and elastographic sonography showed higher sensitivity (87.1%) than B-mode sonography alone. With a strain ratio cutoff point of 2.3, sensitivity was 82.8%, and specificity was 56.3%. CONCLUSIONS: Sonographic elastography may increase the sensitivity of B-mode sonography in the detection of metastatic axillary lymph nodes.

Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast.

BACKGROUND: Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer. METHODS: DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction. RESULTS: Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001). CONCLUSION: Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.

Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesity.

Obese women have an increased risk for post-menopausal breast cancer. The physiological mechanism by which obesity contributes to breast tumourigenesis is not understood. We previously showed that HCCR-1 oncogene contributes to breast tumourigenesis as a negative regulator of p53 and detection of HCCR-1 serological level was useful for the diagnosis of breast cancer(.) In this study, we found that the HCCR-1 level is elevated in breast cancer tissues and cell lines compared to normal breast tissues. We identified apolipoprotein E (ApoE) interacting with HCCR-1. Our data show that HCCR-1 inhibits anti-proliferative effect of ApoE, which was mediated by diminishing ApoE secretion of breast cancer cells. Finally, HCCR-1 induced the severe obesity in transgenic mice. Those obese mice showed severe hyperlipidaemia. In conclusion, our results suggest that HCCR-1 might play a role in the breast tumourigenesis while the overexpression of HCCR-1 induces the obesity probably by inhibiting the cholesterol-lowering effect of ApoE. Therefore, HCCR-1 seems to provide the molecular link between the obesity and the breast cancer risk.

Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status.

BACKGROUND: Oncoprotein HCCR-1 functions as a negative regulator of the p53 and contributes breast tumorigenesis. The serum HCCR-1 assay is useful in diagnosing breast cancer and mice transgenic for HCCR developed breast cancers. But it is unknown how HCCR-1 contributes to human breast tumorigenesis. METHODS: Oncogene HCCR-1 expression levels were determined in normal breast tissues, breast cancer tissues and cancer cell lines. We examined whether HCCR-1 protein expression in breast cancer is related to different biological characteristics, including ER, PR, p53 genotype, and HER2 status in 104 primary breast cancer tissues using immunohistochemical analyses. RESULTS: HCCR-1 was upregulated in breast cancer cells and tissues compared with normal breast tissues. In this study, overexpression of HCCR-1 was well correlated with known breast cancer prognostic markers including the presence of steroid receptors (ER and PR), p53 mutation and high HER2 overexpression. HCCR-1 was not detected in the ER-negative, PR-negative, p53 negative and low HER2 breast cancer tissues. These data indicate that the level of HCCR-1 in breast cancer tissues is relatively well correlated with known breast cancer factors, including the HER2 overexpression, p53 mutation, and ER/PR status. CONCLUSION: Determination of HCCR-1 levels as options for HER2 testing is promising although it needs further evaluation.