Video-assisted thoracic surgery (VATS) for resection of metastatic adenocarcinoma as an acceptable alternative

Adenocarcinomas commonly metastasize to the lungs and can be resected using open thoracotomy or video-assisted thoracic surgery (VATS). This study reviews metastatic resections in primary adenocarcinoma patients, using both thoracotomy and VATS. We aim to compare long-term prognoses to test the efficacy and viability of VATS. A retrospective review of primary adenocarcinoma patients who underwent resection of pulmonary metastases from 1990 to 2006 was carried out. Information was obtained by chart review. Endpoints analyzed were disease-free interval (DFI), survival time, and recurrence-free survival (RFS). In a total of 42 (16 male, 26 female; median age 58.5 years) primary adenocarcinoma patients, 21 patients underwent first pulmonary metastatic resection using VATS (7 male, 14 female; median age 57 years) and 21 using thoracotomy (9 male, 12 female; median age 59 years). Primary adenocarcinomas were mainly 27 colorectal (64%) and 11 breast (26%). Two VATS (10%) and three open patients (14%) had local recurrences of the original cancer. Median postoperative follow was 13.3 months [interquartile range (IQR) 4.5–32.8 months] for VATS and 36.9 months (IQR 19.3–48.6 months) after thoracotomy. Median DFI–1 was 22.3 months (IQR 13.5–40.6 months) for VATS patients and 35.6 months (IQR 26.7–61.3 months) for open patients. Second thoracic occurrences were noted in six VATS patients (median DFI–2 9.2 months), and in seven open patients (median DFI-2 21.5 months). Third thoracic occurrences were noted in one VATS patient (DFI-3 18.7 months) and in one thoracotomy patient (DFI-3 21.8 months). Odds ratio of recurrence showed 12.5% less chance of developing recurrence in VATS patients. Five-year RFS was 53% in VATS and 57% in thoracotomy patients. VATS has become a viable alternative to open thoracotomy for resection of pulmonary metastases. In cases of primary adenocarcinoma, VATS showed no increase in number of thoracic recurrences, and comparable RFS. Short-term follow-up is encouraging; long-term follow-up will be needed to confirm these results

CA 15-3 is predictive of response and disease recurrence following treatment in locally advanced breast cancer

BACKGROUND: Primary chemotherapy (PC) is used for down-staging locally advanced breast cancer (LABC). CA 15-3 measures the protein product of the MUC1 gene and is the most widely used serum marker in breast cancer. METHODS: We retrospectively investigated the role of CA 15-3 in conjunction with other clinico-pathological variables as a predictor of response and time to disease recurrence following treatment in LABC. Pre and post primary chemotherapy serum concentrations of CA 15-3 together with other variables were reviewed and related to four outcomes following primary chemotherapy (clinical response, pathological response, time to recurrence and time to progression). Persistently elevated CA 15-3 after PC was considered as consecutively high levels above the cut off point during and after PC. RESULTS: 73 patients were included in this study. Patients received PC (AC or AC-T regimen) for locally advanced breast cancer. 54 patients underwent surgery. The median follow up was 790 days. Patients with high concentrations of CA 15-3 before PC treatment had a poor clinical (p = 0.013) and pathological (p = 0.044) response. Together with Her-2/neu expression (p = 0.009) and tumour lympho-vascular space invasion (LVI) (p = 0.001), a persistently elevated CA 15-3 post PC (p = 0.007) was an independent predictive factor of recurrence following treatment in LABC. CONCLUSION: Elevated CA 15-3 level is predictive of a poor response to chemotherapy. In addition, persistently elevated CA 15-3 levels post chemotherapy in conjunction with lympho-vascular invasion and HER2 status predict a reduced disease free survival following treatment in locally advanced breast cancer

p53 as a potential predictive factor of response to chemotherapy: feasibility of p53 assessment using a functional test in yeast from trucut biopsies in breast cancer patients

Assessment of the predictive value of p53 requires the testing of large numbers of samples from patients enrolled in prospective phase III clinical trials. The goal of this study was to determine whether p53 status can be determined by p53 yeast functional assay using the limiting amounts of material that can typically be obtained in prospective phase III trials (particularly when chemotherapy is given before surgery). All patients presenting with a clinically palpable tumour which could be considered large enough to perform a trucut biopsy (⩾2 cm breast tumour) were eligible for this study. Two trucut biopsies and one incisional biopsy were performed on the surgical specimens (mastectomy or tumourectomy). Samples were snap frozen and cryostat sections were taken for histology and p53 testing. Thirty patients were included. Three samples out of 90 failed to give any p53 PCR products, probably because these samples contained almost entirely fibrous tissue. Of the 87 samples that could be tested, the incisional and trucut biopsies results were fully concordant in every case. p53 could be defined in 97% of patients by double trucut biopsy. Eight out of 30 tumours tested were mutant for p53 (27%). p53 status can be reliably determined by yeast assay from single frozen sections of trucut biopsies. Histological examination before p53 testing is essential to exclude cases where the p53 result may reflect only the status of the normal cells in the biopsy

The p53 pathway in breast cancer

p53 mutation remains the most common genetic change identified in human neoplasia. In breast cancer, p53 mutation is associated with more aggressive disease and worse overall survival. The frequency of mutation in p53 is, however, lower in breast cancer than in other solid tumours. Changes, both genetic and epigenetic, have been identified in regulators of p53 activity and in some downstream transcriptional targets of p53 in breast cancers that express wild-type p53. Molecular pathological analysis of the structure and expression of constituents of the p53 pathway is likely to have value in diagnosis, in prognostic assessment and, ultimately, in treatment of breast cancer

HPV infection and p53 and p16 expression in esophageal cancer: are they prognostic factors?

Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a potential risk factor for esophageal cancer (EC) in addition to the classic risk factors, alcohol and tobacco, but this hypothesis still remains contradictory. We sought to investigate wether HPV and well-known biomarkers (p16 and p53) and patient-related factors that may have impact on survival of ESCC. Methods: We conducted a prospective cohort study. By using multiplex PCR, we determined the prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical expression of p16 and p53, molecular markers related to esophageal carcinogenesis in order to verify the potential influence of these variables in patients's survival. Survival rates were estimated using Kaplan-Meier methods. A multivariate confirmatory model was performed using Cox proportional hazards regression. Results: Twelve (13.8%) of 87 patients were HPV-DNA positive. Positive reactions of p16 and p53 were 10.7% and 68.6%, respectively. Kaplan-Meier analysis indicated that men (p = 0.025) had poor specific-cancer survival and a shorter progression-free survival (p = 0.050) as compared to women; III or IV clinical stage (p < 0.019) had poor specific-cancer survival and a shorter progression-free survival (p < 0.001) compared to I and II clinical stage; not submitted to surgery (< 0.001) and not submitted to chemoradiotherapy (p = 0.039) had a poor specific-cancer survival, as well. The multivariate analysis showed that HPV, p16 and p53 status are not predictive parameters of progression-free and specific-cancer survival. Conclusion: HPV infection and p53 and p16 expression are not prognostic factors in ESCC.CNPq Universal for providing supplies to the largest study, of which this study is a part of, entitled “The role of human papillomavirus (HPV) as the etiologic agent of esophageal cancer. A cross-sectional study, case-control and longitudinal at Barretos Cancer Hospital”; (Grant number 482666/2012–9 to ALF); INCT HPV [Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grant number 08/57889–1 to LLV]; Conselho Nacional de Desenvolvimento Científico e Tencnológico (CNPq) (Grant number 573799/ 2008–3 to LLV)].info:eu-repo/semantics/publishedVersio

Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers

<p>Abstract</p> <p>Background</p> <p>Triple-negative breast cancer (estrogen receptor-, progesterone receptor-, and HER2-negative) (TNBC) is a high risk breast cancer that lacks specific therapy targeting these proteins.</p> <p>Methods</p> <p>We studied 969 consecutive Japanese patients diagnosed with invasive breast cancer from January 1981 to December 2003, and selected TNBCs based on the immunohistochemical data. Analyses of epidermal growth factor receptor (<it>EGFR</it>) gene mutations and amplification, and <it>BRCA</it>1 mRNA expression were performed on these samples using TaqMan PCR assays. The prognostic significance of TNBCs was also explored. Median follow-up was 8.3 years.</p> <p>Results</p> <p>A total of 110 (11.3%) patients had TNBCs in our series. Genotyping of the <it>EGFR </it>gene was performed to detect 14 known <it>EGFR </it>mutations, but none was identified. However, <it>EGFR </it>gene copy number was increased in 21% of TNBCs, while only 2% of ER- and PgR-positive, HER2-negative tumors showed slightly increased <it>EGFR </it>gene copy numbers. Thirty-one percent of TNBCs stained positive for EGFR protein by immunohistochemistry. <it>BRCA1 </it>mRNA expression was also decreased in TNBCs compared with controls. Triple negativity was significantly associated with grade 3 tumors, TP53 protein accumulation, and high Ki67 expression. TNBC patients had shorter disease-free survival than non-TNBC in node-negative breast cancers.</p> <p>Conclusion</p> <p>TNBCs have an aggressive clinical course, and <it>EGFR </it>and <it>BRCA1 </it>might be candidate therapeutic targets in this disease.</p

Evaluation of HER2 and p53 expression in predicting response to docetaxel-based first-line chemotherapy in advanced breast cancer

<p>Abstract</p> <p>Background</p> <p>The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer.</p> <p>Methods</p> <p>HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence <it>in situ </it>hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors.</p> <p>Results</p> <p>Median time to progression and overall survival were 9 (range 2 - 54) and 20 (range 3 - 101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (<it>p </it>= 0.05) and higher stage (<it>p </it>= 0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53 ± 10.21 vs 2.50 ± 4.12, <it>p </it>= 0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (<it>p </it>= 0.046). p53 expression was only associated with higher stage disease (<it>p </it>= 0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter.</p> <p>Conclusion</p> <p>Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.</p

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