Prognostic Value of p53 and bcl-2 Expression in Patients Treated with Breast Conservative Therapy

Prognostic value of p53 and bcl-2 expression on treatment outcome in breast cancer patients has been extensively evaluated, but the results were inconclusive. We evaluated the prognostic significance of these molecular markers in patients treated with breast conserving surgery and radiotherapy. One hundred patients whose immunostaining of p53 and bcl-2 expression was available among 125 patients who underwent radiotherapy after breast conserving surgery and axillary lymph node dissection were enrolled into this study. Eighty-seven patients also received adjuvant chemotherapy and/or hormonal therapy. Conventional clinicopathologic variables and treatment-related factors were also considered. The 5-yr loco-regional relapse-free and distant metastasis-free survival rates were 91.7% and 90.9%, respectively. On univariate analysis, age, T stage and the absence of bcl-2 & estrogen receptor (ER) expression were associated with loco-regional relapse-free survival. When incorporating these variables into Cox proportional hazard model, only bcl-2(-)/ER(-) phenotype was an adverse prognostic factor (P=0.018). As for the distant metastasis-free survival, age, T stage, and p53 expression were significant on univariate analysis. However, p53 expression was the only prognosticator on multivariate analysis (P=0.009). A bcl-2(-)/ER(-) phenotype and p53 expression are useful molecular markers predicting loco-regional relapse-free and distant metastasis-free survival, respectively, in patients treated with breast conserving surgery and radiotherapy

Welfare Genome Project: A Participatory Korean Personal Genome Project With Free Health Check-Up and Genetic Report Followed by Counseling.

The Welfare Genome Project (WGP) provided 1,000 healthy Korean volunteers with detailed genetic and health reports to test the social perception of integrating personal genetic and healthcare data at a large-scale. WGP was launched in 2016 in the Ulsan Metropolitan City as the first large-scale genome project with public participation in Korea. The project produced a set of genetic materials, genotype information, clinical data, and lifestyle survey answers from participants aged 20-96. As compensation, the participants received a free general health check-up on 110 clinical traits, accompanied by a genetic report of their genotypes followed by genetic counseling. In a follow-up survey, 91.0% of the participants indicated that their genetic reports motivated them to improve their health. Overall, WGP expanded not only the general awareness of genomics, DNA sequencing technologies, bioinformatics, and bioethics regulations among all the parties involved, but also the general public's understanding of how genome projects can indirectly benefit their health and lifestyle management. WGP established a data construction framework for not only scientific research but also the welfare of participants. In the future, the WGP framework can help lay the groundwork for a new personalized healthcare system that is seamlessly integrated with existing public medical infrastructure

Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy

BACKGROUND: Bcl-2 is positively regulated by hormonal receptor pathways in breast cancer. A study was conducted to assess the prognostic significances of clinico-pathologic variables and of ER, PR, p53, c-erbB2, bcl-2, or Ki-67 as markers of relapse in breast cancer patients who had received the identical adjuvant therapy at a single institution. METHODS: A cohort of 151 curatively resected stage III breast cancer patients (M:F = 3:148, median age 46 years) who had 4 or more positive lymph nodes and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinico-pathologic characteristics including disease-free survival (DFS) and overall survival (OS). Patients with positive ER and/or PR expression received 5 years of tamoxifen following AC/T. The protein expressions of biomarkers were assessed immunohistochemically. RESULTS: The median follow-up duration was 36 months, and 37 patients (24.5%) experienced a recurrence. Univariate analyses indicated that the tumor size (P = 0.038) and the number of involved lymph nodes (P < 0.001) significantly affected the recurrences. However, the type of surgery, the histology, histologic grade, the presence of endolymphatic emboli, and a close resection margin did not. Moreover, ER positivity (P = 0.013), bcl-2 positivity (P = 0.002) and low p53 expression (P = 0.032) were found to be significantly associated with a prolonged DFS. Furthermore, multivariate analysis identified 10 or more involved lymph nodes (HR 7.366; P < 0.001), negative bcl-2 expression (HR 2.895; P = 0.030), and c-erbB2 over-expression (HR 3.535; P = 0.001) as independent indicators of poorer DFS. In addition, bcl-2 expression was found to be significantly correlated with the expressions of ER and PR, and inversely correlated with the expressions of p53, c-erbB2 and Ki-67. Patients with bcl-2 expression had a significantly longer DFS than those without, even in the ER (+) subgroup. Moreover, OS was significantly affected by ER, bcl-2 and c-erbB2. CONCLUSION: Bcl-2 is an independent prognostic factor of DFS in curatively resected stage III breast cancer patients and appears to be a useful prognostic factor in combination with c-erbB2 and the number of involved lymph nodes

Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Prognostic factors in locally advanced breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive and prognostic factors in breast cancer patients treated by neoadjuvant chemotherapy.</p> <p>Methods</p> <p>A total of 145 stage II and III breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors (ER, PR, p53, c-erbB2, bcl-2, and Ki-67) by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters.</p> <p>Results</p> <p>Among the clinicopathologic parameters investigated, none of the marker was correlated with response rate (RR) except triple negative phenotype. Patients with triple negative phenotype showed higher RR (83.0% in triple negative <it>vs</it>. 62.2% in non-triple negative, <it>p </it>= 0.012) and pathologic complete RR (17.0% in triple negative <it>vs</it>. 3.1% in non-triple negative, <it>p </it>= 0.005). However, relapse free survival (RFS) and overall survival (OS) were significantly shorter in triple negative breast cancer patients (<it>p </it>< 0.001, <it>p </it>= 0.021, respectively). Low histologic grade, positive hormone receptors, positive bcl-2 and low level of Ki-67 were associated with prolonged RFS. In addition, positive ER and positive bcl-2 were associated with prolonged OS. In our homogeneous patient population, initial clinical stage reflects RFS and OS more precisely than pathologic stage. In multivariate analysis, initial clinical stage was the only significant independent prognostic factor to impact on OS (hazard ratio 3.597, <it>p </it>= 0.044).</p> <p>Conclusion</p> <p>Several molecular markers provided useful predictive and prognostic information in stage II and III breast cancer patients treated with neoadjuvant docetaxel/doxorubicin chemotherapy. Triple negative phenotype was associated with shorter survival, even though it was associated with a higher response rate to neoadjuvant chemotherapy.</p

The sequencing of chemotherapy and radiotherapy in breast cancer patients after mastectomy

Background. The purpose of the study was to retrospectively evaluate the outcome according to the sequencing of radiotherapy and chemotherapy after mastectomy in high-risk patients with breast cancer. Methods. From January 1986 through September 2000, 275 women with stage I-IIIB breast cancer were treated with chemotherapy and radiotherapy after mastectomy The patients were divided into four groups. Chemotherapy was given first in 116 patients (CTRT), concurrent chemoradiotherapy in 77 (CCRT), sandwich therapy in 65 (SAND), and radiotherapy first in 17 (RTCT). Prognostic factors such as age, primary tumor size and nodal status were not statistically different among the four groups. There was a higher proportion of patients with close or positive margins in CCRT and RTCT groups than in the CTRT and SAND groups (22/77, 5/17 vs 3/116, 2/65, P<0.001). Results. Median follow-up was 145 months (range, 10-210). Five-year overall and disease-free survival were 69.4% and 56.1%, respectively Survival outcomes were not statistically different among the four groups (5-year overall/disease-free survival, 68.0%/63.0%, 71.3%/60.8%, 65.0%/48.1%, 81.9%/58.8%, in CTRT, CCRT, SAND, and RTCT, respectively) (P = 0.3422/P = 0.6333). The incidence of local-regional recurrence was not different in the early radiotherapy group (CCRT/RICT, 11%/12%) and delayed radiotherapy group (CTRT/SAND, 7%/8%). Conclusions. This study suggests that in these high-risk breast cancer patients after mastectomy, delay in the start of radiotherapy does not increase local-regional recurrence, and the final survival outcomes are not affected by the sequencing of chemotherapy and radiotherapy.Piroth MD, 2008, BMC CANCER, V8, DOI 10.1186/1471-2407-8-114Goldhirsch A, 2005, ANN ONCOL, V16, P1569, DOI 10.1093/annonc/mdi326BELTON JR, 2005, CLIN ONCOL, V23, P1934White J, 2004, INT J RADIAT ONCOL, V60, P77, DOI 10.1016/j.ijrobp.2004.02.035RECHT A, 2003, CLIN BREAST CANCER, V11, P4Hebert-Croteau N, 2002, BREAST CANCER RES TR, V74, P77CALAIS G, 2002, INT J RADIAT ONCOL, V54, P57Recht A, 2001, J CLIN ONCOL, V19, P1539Metz JM, 2000, CANCER J, V6, P324Overgaard M, 1997, NEW ENGL J MED, V337, P949Ragaz J, 1997, NEW ENGL J MED, V337, P956Olson JE, 1997, CANCER, V79, P1138Recht A, 1996, NEW ENGL J MED, V334, P1356HARTSELL WF, 1995, CANCER, V76, P2497LEONARD CE, 1995, J CLIN ONCOL, V13, P2906BUZDAR AU, 1993, CANCER, V71, P3680BUCHHOLZ TA, 1993, INT J RADIAT ONCOL, V26, P23GRIEM KL, 1987, J CLIN ONCOL, V5, P1546

The sequencing of chemotherapy and radiotherapy in breast cancer patients after mastectomy

Background. The purpose of the study was to retrospectively evaluate the outcome according to the sequencing of radiotherapy and chemotherapy after mastectomy in high-risk patients with breast cancer. Methods. From January 1986 through September 2000, 275 women with stage I-IIIB breast cancer were treated with chemotherapy and radiotherapy after mastectomy The patients were divided into four groups. Chemotherapy was given first in 116 patients (CTRT), concurrent chemoradiotherapy in 77 (CCRT), sandwich therapy in 65 (SAND), and radiotherapy first in 17 (RTCT). Prognostic factors such as age, primary tumor size and nodal status were not statistically different among the four groups. There was a higher proportion of patients with close or positive margins in CCRT and RTCT groups than in the CTRT and SAND groups (22/77, 5/17 vs 3/116, 2/65, P<0.001). Results. Median follow-up was 145 months (range, 10-210). Five-year overall and disease-free survival were 69.4% and 56.1%, respectively Survival outcomes were not statistically different among the four groups (5-year overall/disease-free survival, 68.0%/63.0%, 71.3%/60.8%, 65.0%/48.1%, 81.9%/58.8%, in CTRT, CCRT, SAND, and RTCT, respectively) (P = 0.3422/P = 0.6333). The incidence of local-regional recurrence was not different in the early radiotherapy group (CCRT/RICT, 11%/12%) and delayed radiotherapy group (CTRT/SAND, 7%/8%). Conclusions. This study suggests that in these high-risk breast cancer patients after mastectomy, delay in the start of radiotherapy does not increase local-regional recurrence, and the final survival outcomes are not affected by the sequencing of chemotherapy and radiotherapy Free full text available at www.tumorionline.i

Metaplastic Breast Carcinoma: Clinicopathologic Features and Prognostic Value of Triple Negativity

Metaplastic breast carcinomas (MBC) are a rare type of breast cancer and are generally characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) negativity. There is a paucity of information on prognosis according to hormone receptor and HER2 expression for these rare tumors. The aim of this study was to compare the clinical features and prognosis between triple-negative metaplastic carcinoma (TNMC) and non-triple-negative metaplastic carcinoma (NTNMC). We retrospectively analyzed MBC patients treated at Seoul National University Hospital between 1996 and 2006. The medical records were reviewed. Fifty-one patients were identified. At a median follow-up of 40.8 months, the 3-year disease-free survival (DFS) and overall survival (OS) rates were 75.5% and 86.3%, respectively. Non-triple negativity (P = 0.012) correlated significantly with OS in multivariate analysis. Of the 51 patients, 41 (80.4%) had TNMC and 10 (19.6%) had NTNMC. The two groups did not differ significantly by age, tumor size or nodal status. In patients with NTNMC, the positivity rates for estrogen receptor, progesterone receptor and HER2 were 20.0%, 30.0% and 80.0% in NTNMC. The 3-year OS rates in patients with TNMC and NTNMC were 93.4% and 58.2%, respectively (P = 0.007). With respect to DFS, there was no statistically significant difference between patients with TNMC and those with NTNMC (P = 0.149). In MBC, the non-triple-negative group had a poor prognosis compared with the triple-negative group, which is contrary to what has been reported in patients with invasive ductal carcinoma of breast. Further research exploring the mechanism underlying this result is needed.Dent R, 2007, CLIN CANCER RES, V13, P4429, DOI 10.1158/1078-0432.CCR-06-3045HANNA W, 2007, CURR ONCOL, V14, P149Pezzi CM, 2007, ANN SURG ONCOL, V14, P166, DOI 10.1245/s10434-006-9124-7Kim MJ, 2006, HUM PATHOL, V37, P1217, DOI 10.1016/j.humpath.2006.04.015Livasy CA, 2006, MODERN PATHOL, V19, P264, DOI 10.1038/modpathol.3800528Press MF, 2005, CLIN CANCER RES, V11, P6598, DOI 10.1158/1078-0432.CCR-05-0636Barnes PJ, 2005, BREAST CANCER RES TR, V91, P173, DOI 10.1007/s10549-004-7260-yNadji M, 2005, AM J CLIN PATHOL, V123, P21, DOI 10.1309/4WV79N2GHJ3X1841Foulkes WD, 2003, J NATL CANCER I, V95, P1482, DOI 10.1093/jnci/djg050Khan HN, 2003, EUR J SURG ONCOL, V29, P600, DOI 10.1016/S0748-7983(03)00107-0KUROKAWA H, 2003, CLIN CANCER RES, V9, P511Bellino R, 2003, ANTICANCER RES, V23, P669Perou CM, 2000, NATURE, V406, P747Rayson D, 1999, ANN ONCOL, V10, P413ROSEN PP, 1997, ROSENS BREAST PATHOLCarlomagno C, 1996, J CLIN ONCOL, V14, P2702HARRIS JR, 1996, DIS BREASTGUTMAN H, 1995, J AM COLL SURGEONS, V180, P193FOSCHINI MP, 1993, SEMIN DIAGN PATHOL, V10, P128TAVASSOLI FAZ, 1992, PATHOL ANNU, V27, P89WARGOTZ ES, 1990, HUM PATHOL, V21, P1142WARGOTZ ES, 1990, CANCER, V65, P272PAIK S, 1990, J CLIN ONCOL, V8, P103WARGOTZ ES, 1989, CANCER, V64, P1490WARGOTZ ES, 1989, HUM PATHOL, V20, P732WARGOTZ ES, 1989, HUM PATHOL, V20, P628CARTER CL, 1989, CANCER, V63, P181REINER A, 1988, CANCER, V61, P1149OBERMAN HA, 1987, AM J SURG PATHOL, V11, P918KAUFMAN MW, 1984, CANCER, V53, P1908