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HER-2/neu Status (her-2/neu + status)
Selected AbstractsChromogenic in situ hybridization analysis of HER-2/neu status in breast carcinoma: Application in screening of patients for trastuzumab (Herceptin®) therapyPATHOLOGY INTERNATIONAL, Issue 8 2001Hiroyuki Kumamoto Evaluation of HER-2/neu status is important in the management of patients with breast carcinoma, especially in determining the possible application of trastuzumab, a humanized anti-HER-2/neu monoclonal antibody. Chromogenic in situ hybridization (CISH) detection of the HER-2/neu oncogene is a newly developed in situ hybridization method that utilizes a robust and unique-sequence DNA probe labeled with digoxygenin, and sequential incubations with antidigoxygenin fluorescein, antifluorescein peroxidase, and diaminobenzidine. In this study, we examined 20 archival specimens of human breast carcinoma using CISH, and we correlated findings with immunohistochemical findings for HER-2/neu. HER-2/neu immunohistochemistry was carried out with HercepTestTM, a standardized immunohistochemical examination system for HER-2/neu overexpression in surgical pathology specimens. CISH analysis could be done in 18 out of 20 cases examined. Gene copy signals for HER-2/neu were recognized as intranuclear brown dots in both neoplastic and non-neoplastic cells. Seven carcinomas showed an increased number or size of signals and were interpreted as being positive for HER-2/neu amplification. Eight cases were positive with the HercepTestTM. Seven out of eight carcinoma cases found to overexpress immunoreactive HER-2/neu also demonstrated HER-2/neu gene amplification following CISH analysis. There was a significant correlation between immunohistochemical and CISH analyses (P< 0.001). We found that CISH was a specific, sensitive and easily applicable method for the detection of HER-2/neu gene amplification, which may be used together with immunohistochemical examination for the evaluation of patients with breast carcinoma. [source] Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasisCANCER, Issue 12 2007Kadri Altundag MD Abstract BACKGROUND. Breast cancer is the second most common cause of central nervous system (CNS) metastases. Several risk factors for CNS metastases have been reported. The objective of the current study was to describe clinicopathologic characteristics and prognostic factors in breast cancer patients with CNS metastases. METHODS. The authors retrospectively evaluated clinical data from 420 patients who had been diagnosed with breast cancer and CNS metastasis between 1994 and 2004 at the University of Texas M. D. Anderson Cancer Center. RESULTS. The median age of the patients at the time of diagnosis of breast cancer was 45 years (range, 25,77 years). Premenopausal and postmenopausal patients were distributed equally. Most patients had invasive ductal histology (91.2%), grade 3 tumors (81.4%) (using the modified Black nuclear grading system), T2 tumor classification (40.1%), and N1 lymph node status (59.7%) diagnosis. Forty percent of patients had estrogen receptor (ER)-positive disease, and 34% had progesterone receptor-positive disease. HER-2/neu status was recorded for only 248 patients, and 39% of the patients in that group had HER-2/neu -positive disease. The most common sites of first metastasis were liver, bone, and lung. CNS metastasis was the site of first recurrence in 53 patients (12%). In total, 329 patients had received either neoadjuvant treatment (113 patients) or adjuvant chemotherapy (216 patients). The majority of those patients (74.4%) had received anthracycline-based regimens. Metastasis was solitary in 111 patients (26.4%), and 29 patients had only leptomeningeal metastases. The median time from breast cancer diagnosis to CNS metastasis was 30.9 months (range, from ,5 months to 216.7 months). The median follow-up after a diagnosis of CNS metastasis was 6 months (range, 7,95.9 months). In all, 359 patients died, and the overall median survival was 6.8 months. Only age at diagnosis and ER status were associated significantly with overall survival in the multivariate analysis. CONCLUSIONS. The current results indicated that the prognosis remains patients with breast cancer metastatic to the CNS. More effective treatment approaches are needed for patients with CNS metastases, even for those with favorable prognostic factors, such as ER-positive tumors or younger age. Cancer 2007. © 2007 American Cancer Society. [source] Race modifies the association between breast carcinoma pathologic prognostic indicators and the positive status for HER-2/neuCANCER, Issue 10 2005Azadeh T. Stark Ph.D. Abstract BACKGROUND Inferences about the variations in the biology of breast carcinoma between African-Americans and Caucasians have been reported. The difference in the prevalence of positive HER-2/neu breast carcinoma was evaluated and the race-specific risk was assessed for positive HER-2/neu among a cohort of women diagnosed with their first primary breast carcinoma, given the accepted prognostic pathologic indicators for positive HER-2/neu status. METHODS Demographic, clinical, and pathologic data were collected from existing databases. The status of HER-2/neu was considered positive if the immunohistochemistry score was 3+ or if the fluorescent in situ hybridization indicated a ratio greater than 2. Multivariable logistic regression was used to determine the race-specific risk for HER-2/neu positive breast carcinoma. RESULTS The difference in the prevalence of HER-2/neu -positive status between African-American and Caucasian women was not statistically significant (P = 0.46). For Caucasian women the likelihood for positive HER-2/neu was statistically significant and increased almost linearly within each stage with nuclear grade dedifferentiation relative to the reference group, women with Stage 1, Grade 1 carcinomas. For African-American women, this risk was not significantly associated with stage, nuclear grade, their interaction term, or other pathologic prognostic indicators. CONCLUSIONS The findings suggest that race modifies the association between the pathologic prognostic indicators of breast carcinoma and the likelihood of HER-2/neu -positive carcinoma. So far, clinical correlative studies of HER-2/neu have not included race as an independent variable. Concerns about the limited generalizability and the need for validation of the findings across racial lines have been expressed previously. Cancer 2005. © 2005 American Cancer Society. [source] Serum HER-2/neu conversion to positive at the time of disease progression in patients with breast carcinoma on hormone therapyCANCER, Issue 2 2005Allan Lipton M.D. Abstract BACKGROUND Prolonged exposure of breast carcinoma cells in vitro to tamoxifen results in tamoxifen resistance. Tamoxifen-resistant cells express increased HER-2/neu mRNA and protein. The objective of this study was to determine whether patients with metastatic or locally advanced breast carcinoma who have negative serum HER-2/neu status at the initiation of first-line hormone therapy with letrozole or tamoxifen convert to positive serum HER-2/neu status at the time of disease progression and to determine whether serum HER-2/neu conversion to positive status is associated with response to therapy and overall survival. METHODS Serum samples were obtained at baseline and at the time of disease progression from 240 patients who initially had negative serum HER-2/neu status (< 15 ng/mL). A manual microtiter, enzyme-linked immunosorbent assay that was specific for the extracellular domain of the HER-2/neu (c- erbB-2) oncoprotein product was used to quantitate serum levels. RESULTS Among 240 patients, 61 patients (26%) converted from serum HER-2/neu negative to positive (> 15 ng/mL) at the time of disease progression. Thirty-two of 129 patients (25%) who were treated with tamoxifen and 29 of 111 patients (26%) who were treated with letrozole became converted to positive serum HER-2/neu status at the time of disease progression. The response rate and the time to disease progression on first-line hormone therapy were not affected by serum HER-2/neu conversion. The survival of patients who converted to positive serum HER-2/neu status was significantly shorter compared with the survival of patients who remained negative for serum HER-2/neu. A multivariate analysis revealed that conversion to positive serum HER-2/neu status was an independent prognostic variable for survival. CONCLUSIONS Conversion to positive serum HER-2/neu status occurred in approximately 25% of patients who received first-line hormone therapy. Conversion to serum HER-2/neu -positive status occurred with equal frequency in antiestrogen and aromatase-inhibitor therapy. The current results showed that serum conversion to HER-2/neu -positive status was an independent risk factor for decreased survival in patients with breast carcinoma. Cancer 2005. © 2005 American Cancer Society. [source] HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinomaCANCER, Issue 11 2005Peter A. Learn M.D. Abstract BACKGROUND The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a , 50% regression in clinical tumor size prior to surgery. RESULTS In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu -negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2,13.0) in favor of docetaxel. Women who had HER-2/neu -negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu -positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu -negative tumors to match that observed in women who have HER-2/neu -positive tumors treated with AC alone. Cancer 2005. © 2005 American Cancer Society. [source] Androgen receptors frequently are expressed in breast carcinomasCANCER, Issue 4 2003Potential relevance to new therapeutic strategies Abstract BACKGROUND Several studies have demonstrated the biologic and therapeutic significance of estrogen and progesterone receptors (ER and PR) in breast carcinomas. The aim of the current study was to examine the presence of androgen receptors (AR) in breast carcinomas. METHODS Two hundred cases of breast carcinoma, consisting of 145 invasive and 55 noninvasive (ductal carcinoma in situ [DCIS]) lesions, were examined using a monoclonal antibody against AR on formalin-fixed, paraffin-embedded archival material. The results were analyzed for correlations with immunohistochemically determined ER, PR, and HER-2/neu expression. RESULTS Eighty-seven of the 145 cases (60%) of invasive carcinoma and 45 of the 55 cases (82%) of DCIS were AR-positive according to internationally standardized guidelines. The vast majority of Grade 1 carcinomas were positive for AR (90% of invasive Grade 1 carcinomas and 95% of Grade 1 DCIS), whereas in Grade 3 invasive carcinomas and DCIS, positive immunoreactions for AR were observed in 46% and 76% of cases, respectively. Among the cases of Grade 3 carcinoma, 33 invasive carcinomas (39%) and 17 DCIS lesions (68%) were ER-negative but AR-positive. Among Grade 1 carcinomas (invasive and DCIS), not a single case was positive for HER-2/neu, but most cases were intensely positive for AR. In contrast, many invasive Grade 3 carcinomas exhibited agreement between AR status and HER-2/neu status (AR-positive and HER-2/neu-positive, 30.5%; AR-negative and HER-2/neu-negative, 42.5%). CONCLUSIONS Androgen receptors are commonly expressed in DCIS and in invasive breast carcinoma. A significant number of poorly differentiated carcinomas are ER-negative and PR-negative but AR-positive. Immunohistochemical examination of AR would be desirable because it would provide additional information about steroid receptors in breast carcinomas. Cancer 2003;98:703,11. © 2003 American Cancer Society. DOI 10.1002/cncr.11532 [source] History of Smoking is Associated with Younger Age at Diagnosis of Breast CancerTHE BREAST JOURNAL, Issue 4 2010Mathew C Abramowitz MD Abstract:, Smoking tobacco has been associated with incidence, response and outcomes after treatment of some cancers. We hypothesized that tobacco use could result in an observable effect on breast cancer stage and characteristics at diagnosis. There were 6,000 patients with Tis-4, N0-3 breast cancers who presented to a comprehensive cancer center at initial diagnosis between 1970 and 2006. Patients were included who had a known smoking history, and subdivided into any tobacco use 2683 (45%) or never tobacco use 3317 (55%). Analyses were performed to evaluate the association of smoking with clinical, pathologic and treatment-related factors at cancer presentation. Median age at diagnosis for all breast cancers was 55 years, for nonsmokers was 56 years, for any smoking history was 55 years, and the subgroup of current smokers was 52 years. The difference in median age for current smokers versus nonsmokers was statistically significant (p < 0.0001). The probability of age <55 years at breast cancer diagnosis for any smoking history compared to nonsmokers was 1.2 for white patients (p < 0.0003) but 0.81 for black patients (p = 0.25). There was no statistically significant association between smoking and T stage, N stage, ER/PR status, or Her-2/neu status, although smokers were less likely to utilize breast-conserving treatment. Smoking was associated with a younger age at diagnosis and lower utilization of breast conservation, and observed in the subgroup of white patients but not black patients. Further efforts to clarify potential reasons for any racial differences and lower utilization of breast conservation with smoking are warranted. [source] | ||||||||||