Acupuncture for the Treatment of Taxane-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Trial.

OBJECTIVES: Some chemotherapy drugs can damage the nerves and cause peripheral neuropathy which is accompanied by severe neuropathic pain or gait impairment. The purpose of this study was to assess the feasibility and the safety of acupuncture for the treatment of peripheral neuropathy following chemotherapy in Korean breast cancer patients. DESIGN: This study was a prospective single-arm observational study using before and after measurements in breast cancer patients presenting with taxane-induced peripheral neuropathy. SETTINGS/LOCATION: This study was performed at East-West Medical Center at Daegu Catholic University Hospital, Daegu, South Korea. INTERVENTIONS: Acupuncture was administered 3 times a week for 4 consecutive weeks, for 25 ± 5 minutes at each session. OUTCOME MEASURES: The primary outcome measure was severity of CIPN using the Neuropathic Pain Symptom Inventory (NPSI) assessed by a self-administered questionnaire and Nerve Conduction Study (NCS) of extremities. The secondary outcome measure was quality of life (QoL) assessed by a self-administered questionnaire using the 36-Item Short From Health Survey (SF-36). RESULTS: Acupuncture significantly reduced the severity of CIPN assessed by NPSI score. Four weeks after the last treatment, the symptoms were not aggravated. According to NCS, 42.9% of participants showed improvement of sensory neuropathy. At the end of the treatment, SF-36 scores were significantly increased for variables including physical functioning, role limitations due to physical health problems, social functioning, and general health perceptions compared to those of baseline measurement. CONCLUSIONS: Acupuncture improved symptoms of CIPN and QoL in Korean women suffering from peripheral neuropathy after chemotherapy using taxane for breast cancer. The effects of acupuncture lasted for at least 1 month after the treatment.

Association between inflammation and cancer stem cell phenotype in breast cancer.

Inflammation and cancer stem cells (CSCs) are becoming increasingly recognized as components of tumorigenesis in breast cancer. In the present study, the association between inflammation and BCSC phenotype was evaluated in human breast cancer tissue. Immunohistochemical staining for cluster of differentiation (CD)24, 44, 4, 8 and 68 was performed using tissue microarray blocks containing 47 consecutive cases of invasive breast carcinoma and 10 normal breast tissue samples. The levels of inflammatory modulators and cytokines, and intratumoral or peritumoral lymphocyte infiltration, were assessed. BCSCs were defined as CD44+/CD24- tumor cells. In total, 21.3% of samples exhibited the CD44+/CD24- phenotype. This phenotype was identified to be significantly inversely associated with lymph node metastasis. In addition, the CD44+/CD24- phenotype was significantly associated with the molecular subtype of breast cancer, and was particularly increased in the basal-like subtype. Furthermore, the CD44+/CD24- phenotype was significantly associated with intratumoral inflammation and tumor-infiltrating CD4+ T cell counts. Notably, tumor-infiltrating CD4+ T cells were significantly increased in patients with the basal-like molecular subtype of breast cancer. In conclusion, the present study identified a significant association between inflammation and the CD44+/CD24- phenotype in breast cancer. These results suggest that the interaction between inflammation and CSCs may affect the tumorigenesis and progression of breast cancer. Further studies are required to clarify the role of inflammation and CSCs in breast cancer.

Prognostic Significance of Activated Leukocyte Cell Adhesion Molecule (ALCAM) in Association with Promoter Methylation of the ALCAM Gene in Breast Cancer.

Activated leukocyte cell adhesion molecule (ALCAM) has been implicated in tumorigenesis. In this study, we studied DNA methylation status of the ALCAM gene using pyrosequencing in breast cancer tissues. We analyzed the association between the methylation status of the ALCAM gene and its expression. Also, the effects of inflammation on the ALCAM gene methylation and its expression were investigated. The ALCAM gene methylation was associated with the ALCAM transcripts in tumor tissues. The methylation status of the ALCAM gene was not significantly different between tumor and normal tissues. The level of ALCAM transcripts was associated with the expression of TNFα, NF-κB p50, IL-4, and intratumoral inflammation. The IHC expression of ALCAM was associated with histologic grade, HER2 overexpression and molecular subtype. The expression of TNFα, NF-κB p50, and IL-4 showed significant association with the clinicopathologic characteristics. In conclusion, the ALCAM gene methylation was related to the level of ALCAM transcripts. Also, the level of ALCAM transcripts was associated with the inflammatory markers in breast cancer. Our results suggest that the methylation of the ALCAM gene contributes to the decreased expression of ALCAM. Also, ALCAM is linked to the inflammatory response in breast cancer.

Difference in F-18 FDG Uptake After Esophagogastroduodenoscopy and Colonoscopy in Healthy Sedated Subjects.

PURPOSE: We aimed to evaluate the difference in fluorodeoxyglucose (FDG) uptake in sedated healthy subjects after they underwent esophagogastroduodenoscopy (EGD) and colonoscopy procedures. METHODS: The endoscopy group (n = 29) included healthy subjects who underwent screening via F-18 FDG positron emission tomography/computed tomography (PET/CT) after an EGD and/or colonoscopy under sedation on the same day. The control group (n = 35) included healthy subjects who underwent screening via PET/CT only. FDG uptake in the tongue, uvula, epiglottis, vocal cords, esophagus, stomach, duodenum, liver, cecum, colon, anus, and muscle were compared between the two groups. RESULTS: Maximum standardized uptake value (SUVmax) in the tongue, pharynx, larynx, and esophagus did not significantly differ between the endoscopy and control groups. In contrast, mean SUVmax in the whole stomach was 18 % higher in the endoscopy group than in the control group (SUVmax: 2.96 vs. 2.51, P = 0.010). In the lower gastrointestinal track, SUVmax from the cecum to the rectum was not significantly different between the two groups, whereas SUVmax in the anus was 20 % higher in the endoscopy group than in the control group (SUVmax: 4.21 vs. 3.50, P = 0.002). SUVmax in the liver and muscle was not significantly different between the two groups. Mean volume of the stomach and mean cross section of the colon was significantly higher in the endoscopy group than in the control group (stomach: 313.28 cm3 vs. 209.93 cm3, P < 0.001, colon: 8.82 cm2 vs. 5.98 cm2, P = 0.001). CONCLUSIONS: EGD and colonoscopy under sedation does not lead to significant differences in SUVmax in most parts of the body. Only gastric FDG uptake in the EGD subjects and anal FDG uptake in the colonoscopy subjects was higher than uptake in those regions in the control subjects.

Metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component causing diagnostic challenges.

BACKGROUND: Breast metastasis from extramammary malignancy is uncommon and often presents diagnostic challenges. Herein, we report a case of a patient with metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component. CASE PRESENTATION: A 47-year-old woman presented with left breast nodule detected on a screening breast ultrasonography. She had surgery for pulmonary adenocarcinoma 3 years ago, and was disease-free state in the follow up studies. The patient was diagnosed with invasive micropapillary carcinoma of the breast by core needle biopsy. She underwent left breast lumpectomy and sentinel lymph node biopsy, and the histologic findings revealed micropapillary carcinoma. Based on the immunohistochemical study, the final diagnosis was solitary breast metastasis from pulmonary adenocarcinoma with micropapillary component. CONCLUSIONS: The diagnosis of metastasis to the breast from extramammary malignancies is difficult but important for proper management and prediction of prognosis. A careful clinical history with a thorough clinical examination is needed to make the correct diagnosis.

Multiple endocrine neoplasia type 1 associated with breast cancer: A case report and review of the literature.

Multiple endocrine neoplasia type 1 (MEN1) is a cancer predisposition syndrome that includes a combination of endocrine and non-endocrine tumors. The present study reports a rare case of MEN1 associated with breast cancer with the MEN1 gene mutation. A 45-year-old female was diagnosed with breast cancer subsequent to presenting with a right breast mass. Pre-operative radiological studies indicated right breast cancer with a suspicious metastatic nodule of the lung. Further studies demonstrated bilateral thyroid nodules, a neuroendocrine tumor of the pancreas, paraganglioma, a left adrenal adenoma, gallstones, uterine subserosal myoma and pituitary macroadenoma. Laboratory examinations revealed hypercalcemia, hypophosphatemia and an increased intact parathyroid hormone level. The workup for the suspected MEN syndrome revealed an increased basal plasma level of insulin-like growth factor-1, prolactin and calcitonin, and an increased 24-h urinary free cortisol level. The patient underwent surgical removal of the breast cancer and the tumors of the pancreas, adrenal gland, thyroid and parathyroid glands, uterus, anterior mediastinum and lung. The pathological diagnosis of the resected breast was of invasive ductal carcinoma. Otherwise the pathological diagnosis was of calcitonin-producing pancreatic endocrine carcinoma, adrenal cortical adenoma, bilateral papillary thyroid carcinomas, parathyroid adenomas, uterine leiomyoma with adenomyosis, a thymic carcinoid tumor and lung hamatoma. Gene analysis was performed to determine the association between gene mutations and the development of tumors in this patient, and a germ-line MEN1 gene mutation was consequently detected. It could be assumed that MEN1 syndrome may have possibly predisposed the present patient to breast cancer. However, additional observations and further studies are required to demonstrate this association.

Breast carcinoma with choriocarcinomatous features: a case report.

Nongestational choriocarcinoma differentiation is extremely rare in breast neoplasms. It is characterized by tumor cells similar to chorionic trophoblastic cells, which react with human placental lactogen and human chorionic gonadotropin (hCG). A 56-year-old woman presented with a palpable right breast mass without past history of trophoblastic tumors. An F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan revealed one focus with low accumulation of FDG in the right breast (maximum standardized uptake value, 1.98). The patient underwent a right mastectomy and biopsy of sentinel nodes. Microscopically, the tumor was a typical invasive ductal carcinoma with multiple foci of choriocarcinoma features. Immunohistochemistry showed that the tumor cells resembling choriocarcinoma were positive for hCG antibody, but negative for HER2/neu, estrogen receptor, and progesterone receptor. A pathologic diagnosis of breast carcinoma with choriocarcinomatous features was made. To our knowledge, this is the first report of invasive carcinoma with choriocarcinomatous features and an unusual finding of low accumulation in an F-18 FDG PET/CT scan in Korea.

Promoter methylation status of the FHIT gene and Fhit expression: association with HER2/neu status in breast cancer patients.

Aberrant DNA methylation has been recognized to contribute to breast carcinogenesis, and promoter hypermethylation of several tumor suppressor genes has been correlated with decreased gene expression. The fragile histidine triad (FHIT) gene is a putative tumor suppressor gene in breast and other types of cancer, and loss of Fhit expression has been observed in breast cancer. The aim of the present study was to evaluate the association between methylation of the FHIT gene and its expression in breast cancer, and to investigate whether methylation and expression of the FHIT gene correlates with clinicopathological characteristics in relation to human epidermal growth factor receptor 2 (HER2) status. Pyrosequencing of bisulfite-treated DNA was performed to study the methylation status of the FHIT gene in 60 breast cancer samples. We examined the expression of Fhit using tissue microarrays by immunohistochemical staining. FHIT methylation was detected in 96.7% and the positive expression rate of Fhit was 87.3% of the patients. The mean methylation level of the FHIT gene was associated with intratumoral inflammation. Methylation level of the FHIT gene had no significant differences according to molecular subtypes. Loss of Fhit expression was associated with large tumor size, basal-like subtype and positive expression of EGFR. In HER2-negative breast cancer, loss of Fhit expression was significantly associated with tumor size, estrogen receptor status and Ki-67 proliferation index. No significant correlation between methylation of the FHIT gene and its expression was observed in the present study. Our results suggest that loss of Fhit expression in breast cancer is associated with poor prognostic features, and it is also relevant to the results in HER2-negative breast cancer. Further studies with larger sample sizes and longer follow-up are required to clarify the predictive and prognostic value of Fhit expression and the FHIT gene methylation status in breast cancer.

Low methylation levels of the SFRP1 gene are associated with the basal-like subtype of breast cancer.

Epigenetic analyses have shown that aberrant DNA methylation signatures are associated with breast cancer molecular subtypes. In this study, we analyzed the methylation status of breast cancer-related genes in relation to the molecular subtypes and investigated whether the basal-like subtype displays distinct methylation profiles. By using pyrosequencing, we analyzed the DNA methylation status of 5 candidate genes in 60 breast cancer samples. We compared the methylation frequency across the molecular subtypes and analyzed the correlation between methylation levels and clinicopathological characteristics. A total of 59 cases displayed aberrant methylation. Amplification during polymerase chain reaction analysis failed in 1 case. The median methylation levels of the secreted frizzled-related protein 1 (SFRP1) gene were significantly lower in the basal-like subtype compared to the luminal A, luminal B and human epidermal growth factor receptor 2 (HER2) subtypes. Cadherin 13 (H-cadherin; CDH13) methylation levels were significantly higher in the HER2 tumors compared to the luminal A and basal-like subtypes. A comparison of the methylation status with clinicopathological characteristics revealed that the expression of bcl-2, progesterone receptor and epidermal growth factor receptor were associated with SFRP1 gene methylation status. Our results indicate that the basal-like subtype is associated with low methylation levels of the SFRP1 gene, suggesting that the methylation levels of specific breast cancer genes may potentially serve as epigenetic biomarkers and prognostic factors.

Acupuncture for the treatment of hot flashes in patients with breast cancer receiving antiestrogen therapy: a pilot study in Korean women.

OBJECTIVES: Antiestrogen therapy can cause vasomotor symptoms similar to those occurring during menopause, including hot flashes. Recent studies suggest that acupuncture is effective in reducing vasomotor symptoms in patients with breast cancer receiving tamoxifen. The purpose of this study was to assess the feasibility and safety of acupuncture for treatment of hot flashes in Korean patients with breast cancer receiving antiestrogen therapy. DESIGN: This was a prospective single-arm observational study using before and after measurements. SETTINGS/LOCATION: The study was located at the East-West Medical Center at Daegu Catholic University Medical Center, Daegu, Korea. SUBJECTS: The subjects were 10 patients with breast cancer who were undergoing antiestrogen therapy with tamoxifen or anastrozole and who were suffering from hot flashes. INTERVENTIONS: Acupuncture was administered 3 times a week for 4 consecutive weeks, for 20±5 minutes at each session. OUTCOME MEASURES: The outcome measure was severity of hot flashes assessed by visual analogue scale (VAS) and total hot flash score. RESULTS: During treatment, severity of hot flashes was reduced by 70%-95% in all patients. Acupuncture significantly alleviated severity of hot flashes assessed by a visual analogue scale (F=30.261; p<0.001) as well as the total hot flash score (F=21.698; p=0.006). Four (4) weeks after the final treatment, symptoms were not aggravated. CONCLUSIONS: Acupuncture appeared to provide effective relief from hot flashes among Korean women receiving antiestrogen therapy after surgery for breast cancer, and the effects lasted for at least 1 month after termination of treatment. A randomized controlled prospective study with a larger sample size is required to clarify the role of acupuncture in the management of hot flashes in Korean patients with breast cancer.

Undifferentiated pleomorphic sarcoma of the male breast causing diagnostic challenges.

Undifferentiated pleomorphic sarcoma of the breast are uncommon and often present diagnostic challenges. Herein, we report a case of the undifferentiated pleomorphic sarcoma occurring in the male breast. A 76-year-old man presented with a palpable bean-sized mass in his left breast for two months. Core needle biopsy revealed the presence of atypical cells in a fibrous proliferative lesion, which was removed by wide excision. Based on examination of the excised tumor, the initial pathologic diagnosis was atypical spindle cell lesion with uncertain malignant potential. One year later, the patient returned with a recurrent mass atthe previous surgical site. The mass was again surgically removed using wide excision. Based on histological findings with immunomarkers, the final diagnosis was undifferentiated pleomorphic sarcoma. Undifferentiated pleomorphic sarcoma of the breast can cause genuine diagnostic difficulty and appropriate immunohistochemistry is mandatory for differential diagnosis.

Expression of leptin, leptin receptor, adiponectin, and adiponectin receptor in ductal carcinoma in situ and invasive breast cancer.

PURPOSE: Adipocytokines, such as leptin, resistin, and adiponectin, are associated with obesity and breast cancer. Several studies have indicated that adipocytokines may influence tumor growth or differentiation. The aims of this study were to determine the expression of leptin, leptin receptor (ObR), adiponectin and adiponectin receptor (AdipoR) in human breast cancer, to evaluate their prognostic significance in the breast cancer. METHODS: Specimens from 198 patients with primary breast cancer were enrolled, and representative paraffin tumor blocks were selected for constructing tissue microarrarys (TMA). Immunohistochemical staining for leptin, ObR, adiponectin, and AdipoR was performed using TMA, and the clinicopathologic characteristics were evaluated from the patient's medical records. RESULTS: Stage 0 breast cancer accounted for 41 cases, and 157 cases were invasive cancer. Positive rates of leptin and ObR expression in the ductal carcinoma in situ (DCIS) group were significantly higher than those of the invasive cancer group (97.4% vs. 34.0%, p<0.001; 74.4% vs. 29.8%, p<0.001). However, positive rates of adiponectin and AdipoR expression in the invasive cancer group were significantly higher than those in the DCIS group (53.7% vs. 33.3%, p=0.024; 59.9% vs. 26.3%, p<0.001). High leptin expression was significantly associated with high Ki-67 expression (p=0.016). High adiponectin expression was significantly correlated with smaller tumor size (p=0.001). CONCLUSION: We suggest that losses of leptin and ObR expression could be associated with invasive cancer, whereas high adiponectin and AdipoR expression may be associated with breast cancer invasiveness.

Ductal carcinoma in situ and sentinel lymph node biopsy.

PURPOSE: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to evaluate whether sentinel lymph node biopsy (SLNB) is required in patients with an initial diagnosis of ductal carcinoma in situ (DCIS). METHODS: A retrospective analysis was performed of 78 patients with an initial diagnosis of DCIS between December 2002 and April 2010 and who proceeded to have either SLNB or axillary node dissection performed as part of their primary surgical procedure. The study focused on the rates of axillary node metastasis and the underestimation of invasive carcinoma at an initial diagnosis. RESULTS: Forty-eight patients underwent SLNB and 18 patients underwent axillary node dissection. Only 1 of 66 patients (1.5%) had a positive sentinel lymph node. After definite surgery, the final diagnosis was changed to invasive ductal carcinoma (IDC) in 12 patients and DCIS with microinvasion in 2 patients; 14 of 78 patients (17.9%) were therefore underestimated at preoperative histological examinations. In 35 patients who were diagnosed DCIS by core needle biopsy (CNB), 13 patients (37.1%) were upstaged into IDC or DCIS with microinvasion in the final diagnosis. The statistically significant factors predictive of invasive breast cancer were a large tumor size and HER2 overexpression. CONCLUSION: The rates of SLNB positivity in pure DCIS are very low, and there is continuing uncertainty about its clinical importance. However in view of the high rate of underestimation of invasive carcinoma in patients with an initial diagnosis of DCIS, SLNB appears to be appropriate in these patients, especially in the case when DCIS is diagnosed by a core needle biopsy. In patients with an initial diagnosis of DCIS by CNB, SLNB should be considered as part of the primary surgical procedure, when preoperative variables show a tumor larger than 2.35 cm and with HER2 overexpression.

Microarray analysis of papillary thyroid cancers in Korean.

BACKGROUND/AIMS: Papillary thyroid cancer (PTC) is the most common malignancy of the thyroid gland. It involves several molecular mechanisms. The BRAF V600E mutation has been identified as the most common genetic abnormality in PTC. Moreover, it is known to be more prevalent in Korean PTC patients than in patients from other countries. We investigated distinct genetic profiles in Korean PTC through cDNA microarray analysis. METHODS: Transcriptional profiles of five PTC samples and five paired normal thyroid tissue samples were generated using cDNA microarrays. The tumors were genotyped for BRAF mutations. The results of the cDNA microarray gene expression analysis were confirmed by real-time PCR and immunohistochemistry analysis of 35 PTC patients. RESULTS: Four of the five patients whose PTC tissues were subjected to microarray analysis were found to carry the BRAF V600E mutation. Microarrays analysis of the five PTC tissue samples showed the expression of 96 genes to be increased and that of 16 genes decreased. Real-time reverse transcription-polymerase chain reaction (RT-PCR) confirmed increased expression of SLC34A2, TM7SF4, COMP, KLK7, and KCNJ2 and decreased expression of FOXA2, SLC4A4, LYVE-1, and TFCP2L1 in PTC compared with normal tissue. Of these genes, TFCP2L1, LYVE-1, and KLK7 were previously unidentified in PTC microarray analysis. Notably, Foxa2 activity in PTC was reduced, as shown by its cytoplasmic localization, in immunohistochemical analyses. CONCLUSIONS: These findings demonstrate both similarities and differences between our results and previous reports. In Korean cases of PTC, Foxa2 activity was reduced with its cytoplasmic accumulation. Further studies are needed to confirm the relationship between FOXA2 and BRAF mutations in Korean cases of PTC.