Lower 5-year Disease-free Survival Rate Research Articles

Low tumour PPM1H indicates poor prognosis in colorectal cancer via activation of cancer-associated fibroblasts

BackgroundVimentin (VIM) is considered a prognostic marker in colorectal cancer (CRC). Our aim is to identify genes that fulfil a “X-low implies VIM-high” Boolean relationship and to evaluate their prognostic value and potential mechanism.MethodsPotential biomarkers related to VIM expression were searched using a bioinformatics approach across gene-expression arrays. Based on subgroup analysis of 2 CRC cohorts, the selected gene was tested for its association with patient’s survival outcomes. The regulatory link between the selected gene and VIM was further examined with in vitro models.ResultsPPM1H was identified as the top candidate in our search. Patients with PPM1H-low tumours have a lower 5-year disease-free survival rate than patients with PPM1H-high tumours in 2 independent cohorts. In multivariate Cox analysis, patients with PPM1H-low tumours were independently associated with relapse in both the discovery cohort (hazard ratio [HR], 1.362; 95% confidence interval [CI], 1.015–1.826; P = 0.039) and the validation cohort (HR for DFS, 4.052; 95% CI, 2.634–6.234; P < 0.001). PPM1H knockdown in CRC cells and growth in the corresponding conditional medium increased VIM expression and colon fibroblast proliferation, indicating a transformation of cancer-association fibroblasts (CAFs). Conversely, educated CAFs also facilitated the growth of CRC cells with low PPM1H expression.ConclusionsLack of tumour PPM1H expression identifies a patient subgroup with a high relapse risk, and CRC cells with low expression of PPM1H activate CAFs and inversely get promoted by CAFs.

Prognostic effects of abnormal DNA damage response protein expression in breast cancer.

We aimed to explore the expression of DNA damage response machinery proteins and their integrated prognostic value in different subgroups of breast cancer. Expression of NBS1, BRCA1, BRCA2, ATM, and p53 was determined by immunohistochemistry in 419 surgically resected breast tumors. Loss of NBS1, BRCA1, ATM, and abnormal p53 expression was significantly associated with lower disease-free survival rates. Abnormal DNA damage response protein expression, defined as loss of any one of NBS1, BRCA1, ATM, and/or abnormal p53 expression, was observed in 258 of 399 evaluable cases (64.7%) and was significantly associated with higher tumor grade, larger tumor size, and ER-negative, and/or PR-negative status. Most patients with luminal B (86.1%), HER2-enriched (94.4%), and triple-negative (86.8%) breast cancers had abnormal DNA damage response protein expression. In contrast, abnormal DNA damage response protein expression was found in only 53.8% of luminal A tumors. Abnormal DNA damage response protein expression was associated with significantly lower 5-year disease-free survival rates in all patients (95.6% vs. 84.8%, p = 0.001), as well as in the luminal A subgroup (97.4% vs. 89.0%, p = 0.011). In multivariate analysis, abnormal DNA damage response protein expression remained an independent predictor of shorter disease-free survival for luminal A subtype (hazard ratio 3.14, 95% confidence interval 1.16-8.47; p = 0.024). Abnormal DNA damage response protein expression is found in most luminal B and HER2-enriched breast cancers as frequently as in triple-negative breast cancer. In the luminal A subtype, abnormal DNA damage response protein expression is an independent prognostic marker.

The Effect of Polymorphism in UGT1A4 on Clinical Outcomes of Adjuvant Tamoxifen Therapy for Patients With Breast Cancer in China

IntroductionUGT1A4 is a major enzyme responsible for the glucuronidation of tamoxifen (TAM) and its metabolites. Genetic variations in the UGT1A4 gene could have a significant impact on the clinical efficacy of TAM. This study was performed to validate the association between UGT1A4 polymorphisms and the clinical outcomes for patients with breast cancer who received adjuvant TAM. Patients and MethodsA total of 773 patients with breast cancer who received adjuvant TAM (n = 321) or aromatase inhibitors (n = 452) at the National Cancer Center in China were analyzed. Through a series of screenings, the single nucleotide polymorphism rs869283 (c.-1180G>A) in the promoter region of the UGT1A4 gene was selected. The associations of rs869283 genotype with disease-free survival (DFS) and clinicopathologic characteristics were analyzed. ResultsA total of 608 (78.7%) patients were wild-type G/G genotype, 154 (19.9%) patients were G/A genotype, and 11 (1.4%) patients were A/A genotype. In the TAM treatment group, patients with A/A or G/A genotype had a lower 5-year DFS rate than those with the wild-type G/G genotype (69.3% vs. 83.7%; P = .031). The rs869283 genotype remained an independent prognostic marker for DFS in multivariate analysis (hazard ratio, 1.74; P = .014). No association between the rs869283 genotype and DFS was found in patients who received AIs (P = .772). ConclusionsOur findings showed that patients with the UGT1A4 rs869283 G/A or A/A genotype received less benefit from adjuvant TAM treatment than those with the G/G genotype. Further studies are warranted to confirm our findings.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Patients with Human Papillomavirus-Positive Oropharyngeal Cancer.

Objective To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) for human papillomavirus-positive oropharyngeal cancer (HPV+ OPC). Study Design Retrospective institutional database analysis. Setting Tertiary referral medical center. Material and Methods In total, 104 patients with HPV+ OPC were enrolled. From the blood laboratory data checked within 4 weeks before initiation of primary treatment, NLR was calculated. The association between clinicopathological characteristics and NLR was analyzed, and the prognostic role was evaluated based on overall survival (OS) and disease-free survival (DFS). Results According to the cutoff value (2.42) for NLR, the patients were classified into the low NLR group (n = 61) or the high NLR group (n = 43). High NLR was associated with a higher rate of advanced T classification ( P = .007) and diabetes mellitus ( P = .01). The proportion of surgery-based treatment was lower in the high NLR group (20.9% vs 42.6%, P = .02). The high NLR group showed a lower 5-year OS rate (85.3% vs 96.3%, P = .09) and a lower 5-year DFS rate (68.1% vs 94.7%, P = .01) than those in the low NLR group. Multivariate analysis showed that advanced N classification was a significant predictor for worse 5-year OS (hazard ratio [HR], 17.40; 95% confidence interval [CI], 2.36-128.29) and that both advanced N classification (HR, 7.78; 95% CI, 2.33-25.93) and high NLR (HR, 4.16; 95% CI, 1.24-13.95) were important prognosticators for worse 5-year DFS. Conclusion Elevated pretreatment NLR was associated with poor DFS in patients with HPV+ OPC.

Abstract 4739: Prognostic impact of abnormal DNA damage response protein expression in breast cancer

Abstract Purpose Defects of DNA damage repair are known to be associated with the efficacy of anthracycline or platinum-based chemotherapy as well as poly[ADP-ribose] polymerase (PARP) inhibitors (PARPi) and PD-1/PD-L1 checkpoint inhibitors. Since multiple proteins are involved in DNA-damage response (DDR) and operate collectively, our main aim was to better understand the expression of proteins in DDR machinery and their integrated prognostic value in the different subtypes of breast cancer. Methods A total of 419 consecutive breast cancer patients who underwent curative resection in 2008 were enrolled in the study. Tissue microarray has been constructed, and NBS1, BRCA1, BRCA2, ATM and p53 expression were determined by immunohistochemistry. Results All patients were female, with a median age of 47 years; 280 (67%) had luminal A, 36 (9%) had luminal B, 37 (9%) had HER2-enriched, and 56 (13%) had triple-negative breast cancer (TNBC). Loss of NBS1, BRCA1, BRCA2, and ATM expression was observed in 6.7%, 33.7%, 89.9%, and 30.8% of breast cancer patients, respectively, and abnormal p53 expression was observed in 39.3% of patients. Loss of NBS1, BRCA1, ATM and abnormal p53 expression was associated with significantly lower disease-free survival (DFS) rates, respectively. “Abnormal DDR protein expression”, defined as loss of any one of NBS1, BRCA1, ATM and/or abnormal p53 expression, was observed in 258 of 399 evaluable cases (64.7%) and was significantly associated with higher tumor grade, larger tumor size, and ER- and/or PR-negative status. Majority of patients with luminal B (31/36, 86.1%), HER2-enriched (34/35, 94.4%), and TNBC (46/53, 86.8%) subtype showed abnormal DDR protein expression. In comparison, 136/264 patients (53.8%) with luminal A subtype had abnormal DDR protein expression. Abnormal DDR protein expression was associated with significantly lower 5-year DFS rate than those in patients with normal DDR protein expression in all patients (95.6% vs. 84.8%, p = 0.001), as well as in luminal A subgroup (97.4% vs. 89.0%, p = 0.011). In multivariate analysis, abnormal DDR protein expression remained as an independent predictor of shorter DFS for luminal A subtype tumors (hazard ratio 3.14; 95% confidence interval, 1.16 – 8.47, p = 0.024). Conclusion We demonstrated differential expression of proteins in DDR machinery according to breast cancer subtypes and its prognostic implication. Most of luminal B and HER2-enriched tumors has abnormal DDR expression as frequently as triple negative tumors. Less but significant proportion of luminal A tumors also shows abnormal DDR protein expression, which is an independent poor prognostic factor. Citation Format: Koung Jin Suh, Han Suk Ryu, Kyung-Hun Lee, Hyojin Kim, Ahrum Min, Tae-Yong Kim, Hyeong-Gon Moon, Sae-Won Han, Do-Youn Oh, Wonshik Han, In Ae Park, Dong-Young Noh, Seock-Ah Im. Prognostic impact of abnormal DNA damage response protein expression in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4739. doi:10.1158/1538-7445.AM2017-4739

Comparison of Treatment Outcomes between Breast Conserving Surgery Followed by Radiotherapy and Mastectomy Alone in Patients with T1-2 Stage and 1-3 Axillary Lymph Nodes in the Era of Modern Adjuvant Systemic Treatments.

PurposeThe role of postmastectomy radiotherapy in the treatment of T1–2 primary tumor with 1–3 positive lymph nodes is controversial. We compared treatment outcomes between breast conserving surgery followed by radiotherapy (BCS+RT) and total mastectomy alone (TM) in the setting of modern adjuvant systemic treatments.MethodsPatients with T1–2 primary breast cancer and 1–3 positive lymph nodes who were treated between 2001 and 2011 were divided into 2 groups based on the treatment approach: BCS+RT (n = 169) and TM (n = 117). All patients received adjuvant chemotherapy including taxanes. Adjuvant endocrine therapy was administered to patients with positive hormone receptors according to their menstrual status.ResultsDuring a median follow-up of 76.5 months, 21 patients (7.3%) experienced locoregional recurrence as the first event, including 7 patients (4.1%) in the BCS+RT group and 14 patients (12.0%) in the TM group. The 5-year cumulative incidence rate of locoregional recurrence was 2.5% for BCS+RT versus 9.5% for TM (p = 0.016). Competing risk regression analysis revealed that TM was associated with a relative risk for locoregional recurrence of 5.347 (p = 0.003). TM was also associated with a significantly lower 5-year disease-free survival rate compared with BCS+RT (hazard ratio, 2.024; 95% confidence interval, 1.090–3.759; p = 0.026).ConclusionTo improve treatment outcomes for TM even after modern systemic treatments, postmastectomy radiotherapy might be required for patients with T1–2 primary breast cancer and 1–3 positive lymph nodes.

Prognostic evaluation of tumor-stroma ratio in patients with early stage cervical adenocarcinoma treated by surgery.

The tumor-stroma ratio (TSR) represents the percentage of neoplastic cell components compared to the combined area of neoplastic cells and the surrounding tumor-induced stroma. A low TSR (predomination of stromal component) has been demonstrated to be an independent adverse prognostic factor in cancers of several organs. In cervical carcinoma patients, TSR has been evaluated in only one previous study with different histological types. The present study aimed to assess the prognostic value of TSR in early stage cervical cancer patients with adenocarcinoma histology only. Histological slides of patients with early stage (IB-IIA) cervical adenocarcinoma who underwent surgical treatment between January 2003 and December 2011 were reviewed. Patients who had received preoperative chemotherapy were excluded. TSR was categorized as low (<50%) and high (≥50%). Correlations between TSR and clinicopathological variables were evaluated. Prognostic values of TSR and other variables were estimated using Cox's regression. Of 131 patients; 38 (29.0%) had low TSR and 93 (71.0%) had high TSR. The patients with low TSR had significantly higher proportions of deep cervical stromal invasion (outer third of wall, p=0.011; residual stroma less than 3 mm, p=0.008) and parametrial involvement (p=0.026). Compared to the patients with high TSR, those with low TSR tended to have lower 5-year disease-free survival rate (83.8% versus 88.9%) and overall survival rate (85.6% versus 90.3%), although the differences were not statistically significant. Low TSR was significantly associated with decreased overall survival in univariate analysis (HR 2.7; 95% CI 1.0-7.0; p=0.041), but not in multivariate analysis. TSR was not significantly associated with decreased disease-free survival. Low TSR is associated with decreased overall survival in patients with early stage cervical adenocarcinoma treated by surgery. However, it was not found to be an independent prognostic predictor in this study.

Covering the Cover

Covering the Cover

Reduced Expression of DKK3 Is Associated With Adverse Clinical Outcomes of Uterine Cervical Squamous Cell Carcinoma

The aim of this study was to assess the expression of DKK3 protein and its target, beta-catenin, in uterine cervical squamous cell carcinoma and to determine potential clinical correlations. Six carcinoma in-situ (CIS) tissues and 88 invasive cervical cancer tissues were included in the study. Twenty-two normal cervical tissues and one gastric cancer tissue were used as controls. The expression of DKK3 and beta-catenin proteins was evaluated by immunohistochemical analysis. Clinical and pathological parameters were obtained from medical records. Survival data were estimated using Kaplan-Meier estimates and compared with a log-rank test. Multivariate analysis was performed using the Cox regression method. DKK3 was predominantly present in the cytoplasm. Beta-catenin was observed only on the cellular membrane of both normal and cancer cells in contrast to earlier reports, in which beta-catenin was localized to the cytoplasm and nucleus of cancer cells. The expressions of beta-catenin and DKK3 were not correlated. Three of 6 CIS (50%) and 57 of 88 invasive cancer specimens (64.8%) had lower DKK3 expression than normal controls. DKK3 expression was decreased in a stage-dependent manner (P = 0.021). The patients with low expression of DKK3 were older than those with high expression of DKK3 (P < 0.01). Moreover, the patients with low DKK3 expression had a significantly lower 5-year disease-free survival rate than those with high DKK3 expression (P = 0.026). A multivariate analysis showed that International Federation of Gynecology and Obstetrics clinical stage and parametrial involvement were independent prognostic factors. Decreased DKK3 expression was associated with advanced International Federation of Gynecology and Obstetrics clinical stages and was predictive of lower disease-free survival in patients with cervical squamous cell carcinoma. DKK3 may be implicated in cervical carcinogenesis through a beta-catenin-independent mechanism.

Clinical significance of granulocytic sarcoma in adult patients with acute myeloid leukemia

To investigate the clinical significance of granulocytic sarcoma (GS) in adults with acute myeloid leukemia (AML), 434 consecutive patients with AML were analyzed retrospectively. Forty-five patients (10.4%) with GS at diagnosis were younger (P < 0.001), presented with higher white blood cell counts (P = 0.03) and were more likely to conform to French-American-British M4 (P = 0.001) and M5 (P = 0.045) classifications than those without GS. In contrast, no significant difference in frequency of cytogenetic abnormalities was found between the GS and non-GS groups. Treatment outcomes in 260 patients (40 with GS) who underwent intensive chemotherapy, excluding patients with acute promyelocytic leukemia, were investigated. Complete remission rates did not differ significantly between the GS and non-GS groups (75.0% vs 79.1%; P = 0.192, respectively) or the 5-year overall survival (OS) rates (39.9% vs 38.7%; P = 0.749, respectively). However, the GS group had a significantly higher relapse rate than the non-GS group (74.2% vs 55.3%; P = 0.048) and a significantly lower 5-year disease-free survival rate (8.2% vs 25.7%, respectively; P = 0.005). When considered together with the results of multivariate analysis, which identified the presence of GS as an independent predictor for disease-free survival time, these findings indicate that GS might identify a high-risk subset of patients with AML.

Association Between African American Race and Outcomes in Patients With Nonmetastatic Triple-Negative Breast Cancer: A Retrospective Analysis by Using Results From the Georgia Cancer Specialist Database

IntroductionThe objective of this study was to evaluate, in a real-world context, the impact of race on disease recurrence and survival in patients with nonmetastatic triple-negative breast cancer (TNBC) treated with adjuvant chemotherapy. Patients and MethodsThe study selected patients from the 2003-2008 Georgia Cancer Specialist Database with stage I-III confirmed TNBC who had received adjuvant chemotherapy. These patients were followed-up from initial diagnosis to death, cancer recurrence, or loss to follow-up. The primary outcome was disease-free survival (DFS). Kaplan-Meier curves compared DFS and recurrence between African American and non-African American groups. The impact of African American status was examined further through multivariate Cox models by adjusting for age, comorbidity, body mass index (BMI), smoking status, initial TNBC stage, surgery, and radiation therapy. ResultsAmong 209 patients with TNBC, 89 (42.6%) were African American. The 2 groups (African American vs. non–African American) were similar in mean age at diagnosis (53.2 vs. 54.4 years; P =.487) and with surgery and radiation rates (98.9% vs. 100%; P = .244; 68.5% vs. 62.5%; P = .365, respectively). Compared with non–African Americans, African American patients had a higher BMI (30.4 vs. 28.6 kg/m2; P = .0477) and were less likely to be diagnosed at stage I (31.5% vs. 51.7%; P = .0107). The African American patients had a lower 5-year DFS rate (45.2% vs. 79.7%; P = .0005) and a higher 5-year recurrence rate (42.5% vs. 7.0%; P = .0005) compared with the non–African American patients. ConclusionsAmong patients with TNBC treated with adjuvant chemotherapy, African American race was associated with a worse outcome irrespective of later stage at presentation or higher BMI.

Overexpression of lysine specific demethylase 1 predicts worse prognosis in primary hepatocellular carcinoma patients

To investigate the clinicopathological features and prognostic value of lysine specific demethylase 1 (LSD1) in hepatocellular carcinoma (HCC). We examined LSD1 expression in 60 paired liver cancer tissues and adjacent noncancerous tissues by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting. In addition, we analyzed LSD1 expression in 198 HCC samples by immunohistochemistry. The relationship between LSD1 expression, clinicopathological features and patient survival was investigated. Immunohistochemistry, Western blotting, and qRT-PCR consistently confirmed LSD1 overexpression in HCC tissues compared to adjacent non-neoplastic tissues (P < 0.01). Additionally, immunostaining showed more LSD1-positive cells in the higher tumor stage (T3-4) and tumor grade (G3) than in the lower tumor stage (T1-2, P < 0.001) and tumor grade (G1-2, P < 0.001), respectively. Moreover, HCC patients with high LSD1 expression had significantly lower 5-year overall survival rates (P < 0.001) and lower 5-year disease-free survival rates (P < 0.001), respectively. A Cox proportional hazards model further demonstrated that LSD1 over-expression was an independent predictor of poor prognosis for both 5-year disease-free survival [hazards ratio (HR) = 1.426, 95%CI: 0.672-2.146, P < 0.001] and 5-year overall survival (HR = 2.456, 95%CI: 1.234-3.932, P < 0.001) in HCC. Our data suggest for the first time that the overexpression of LSD1 protein in HCC tissues indicates tumor progression and predicts poor prognosis.

Feasibility of Preservation of the Submandibular Gland During Neck Dissection in Patients With Early-Stage Oral Cancer

The impact of submandibular gland (SMG) preservation during neck dissection on the survival of patients with early-stage oral squamous-cell carcinoma (OSCC) remains undocumented. The medical records of all patients with early-stage OSCC (stage I and II) who underwent wide excision of the primary tumor and simultaneous neck dissection between 1999 and 2006 at our facility were retrospectively reviewed. We analyzed 408 patients, including 33 patients with and 375 patients without SMG preservation. The 5-year disease-free and overall survival rates were 78.8% and 90.9% for the patients with SMG preservation and 75.4% and 90.4% for the patients without SMG preservation, and these differences were not statistically significant (P=0.79, P=0.99, respectively). Similar survival rates between patients with and without SMG preservation were observed in those with oral tongue squamous-cell carcinoma (SCC) and with buccal SCC. Patients with T2 OSCC with SMG preservation had significantly lower 5-year disease-free survival rate than those without SMG preservation (P=0.02), but overall survival rates were similar between these two groups. Preservation of the SMG during neck dissection may be oncologically safe in patients with T1 OSCC, but the feasibility of SMG preservation seems less clear for T2 OSCC.

Association of black race and outcomes in patients with nonmetastatic triple-negative breast cancer (TNBC): Results from a U.S. local oncology practice.

6107 Background: TNBC carries a poor prognosis. African American (AA) race has been shown as an adverse prognostic factor in many cancers. The objective of this study was to evaluate, in a real-world context, the impact of AA on disease recurrence and survival among nonmetastatic TNBC patients treated with adjuvant chemotherapy (CT). Methods: The Georgia Cancer Specialist Database (2003- 2008) was used. Patients with stage (I-III) BC, confirmed TN status, treated with adjuvant CT were followed from initial BC diagnosis to the earliest of death, BC recurrence, or loss to follow-up. The primary outcome was disease-free survival (DFS). The secondary outcome was recurrence. DFS and recurrence were compared between AA and non-AA groups with Kaplan-Meier curves. The impact of AA status was further examined using multivariate Cox models adjusting for age, comorbidity, BMI, smoking status, initial BC stage, surgery, and radiation therapy. Results: Among 209 TNBC patients, 89 (42.6%) were AA. The two groups (AA vs. non-AA) were similar in mean age at BC diagnosis (53.2 vs. 54.4, p = 0.487), surgery and radiation rates (98.9% vs. 100%, p = 0.244; 68.5% vs. 62.5%, p = 0.365, respectively). Compared to non-AA, AA patients were more obese (BMI: 30.4 vs. 28.6, p=0.048), and more likely to be diagnosed at stage II (stage I: 31.5% vs. 51.7%; stage II: 64.0% vs. 43.3%; stage III: 4.5% vs. 5.0%; p = 0.0107). Compared to non-AA, AA patients had lower 5-year DFS rate (45.2% vs. 79.7%, p = 0.0005), and higher 5-year recurrence rate (42.5% vs. 7.0%, p = 0.0005). The median DFS was significantly shorter for AA than non-AA patients (615 vs. 775 days, p = 0.0005). The multivariate Cox models showed that AA was associated with lower likelihood for DFS (HR = 0.15, p = 0.0005), and higher risk for recurrence (HR = 8.16, p = 0.0006), compared to non-AA patients. Conclusions: This study suggested that AA race was associated with worse outcomes irrespective of later stage at presentation among TNBC patients who were treated with currently available adjuvant CT. Future studies need to explore genotypic as well as behavioral reasons for inferior outcomes associated with AA race. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis

Impact of anastomotic leakage on oncological outcome after rectal cancer resection

: Anastomotic leakage has a major impact on morbidity and mortality in rectal cancer surgery. Its relevance to oncological outcome is controversial. This observational study investigated the influence of anastomotic leakage on oncological outcome. : Data for 1741 patients undergoing curative resection of rectal cancer (located less than 12 cm from the anal verge) with normal healing were compared with those for 303 patients who experienced anastomotic leakage. Morbidity, mortality and long-term oncological outcomes were analysed. : Median follow-up was 40 months. Patients with anastomotic leakage had a higher postoperative mortality rate than those with no leakage (4.3 versus 1.2 per cent; P < 0.001). Patients with leakage necessitating surgical treatment had a higher 5-year local recurrence rate (17.5 versus 10.1 per cent; P = 0.006) and a lower 5-year disease-free survival rate (70.9 versus 75.4 per cent; P = 0.020) than those without leakage. Patients with anastomotic leakage not requiring surgical intervention did not have a worse oncological outcome. : A negative prognostic impact of anastomotic leakage on local recurrence and disease-free survival was found only for patients with leakage needing surgical revision.

Clinical Features and Treatment Outcome of Hispanic Men With Prostate Cancer Following External Beam Radiotherapy

We retrospectively analyzed the clinical characteristics and outcomes of Hispanic men compared with other groups who underwent radiotherapy alone for localized or locally advanced prostate cancer. Between April 1987 and January 1998, 964 men who underwent full dose external beam radiotherapy alone for localized or locally advanced prostate cancer were included in the study. Patient medical records were reviewed for pertinent information. Of the 964 men 810 were non-Hispanic white, 54 were Hispanic and 86 were black Americans. The most significant difference among the groups was in the proportion of patients who presented with initial prostate specific antigen (PSA) greater than 20 ng/ml (22% of Hispanic vs 11% of white men, p = 0.0012). In addition, 17% of Hispanic men had a Gleason score of 8 or greater compared with 11% of white men (p = 0.0265). A greater proportion of Hispanic patients also had a less favorable posttreatment PSA nadir of greater than 1 ng/ml compared with white patients, (44% vs 26%, p = 0.0214), which may have translated into a trend toward a lower 5-year disease-free survival rate in Hispanics vs white men (52% vs 65%, p = 0.07). Hispanic men presented with higher PSA and higher grade prostate cancer than white men. Furthermore, a higher percent of Hispanic men had a PSA nadir of 1 ng/ml or greater after radiotherapy, which may have been responsible for their trend toward a decreased 5-year disease-free survival rate compared with white men. Improved screening and early detection may improve disease-free survival in Hispanic men with localized prostate cancer.

Prognostic implications of pathological lymph node status after preoperative chemotherapy for operable T3N0M0 breast cancer.

Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo. Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years. Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P = .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P = .01) and disease-specific survival (P = .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4-9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4-9 positive nodes (17 vs. 48%, P = .04). Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.

Ki-67 Expression is a Prognostic Marker of Prostate Cancer Recurrence after Radical Prostatectomy

Purpose We assessed the cellular proliferation of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody MIB to Ki-67 antigen in an attempt to identify associations between proliferative indexes and disease progression following radical prostatectomy. Materials and Methods Ki-67 proliferative antigen was evaluated using MIB 1 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 180 patients followed for 1 to 9 years (mean 4.4). The percentage of tumor nuclei expressing Ki-67 antigen was measured and assigned an MIB 1 score (none or rare-negative, 1+-low score and 2 to 4+-high score) and analyzed for prostate specific antigen, stage, age, race, grade and serological recurrence postoperatively. Results There was a significant association between MIB 1 score and nuclear grade (p less than 0.001), Gleason score (p less than 0.001) and pathological stage (p = 0.01). Patients with a high MIB 1 score had earlier progression and a lower 5-year recurrence-free survival rate (44 percent) than those with negative MIB 1 scores (71 percent, p less than 0.001). In multivariate Cox regression analysis with backward elimination, pathological stage (p less than 0.01), pretreatment prostate specific antigen (p = 0.04) and MIB 1 score (p = 0.05) were statistically significant predictors of disease-free survival, and patients with a high MIB 1 score were 3.1 times as likely to have recurrence as those with a negative score. Controlling for stage, patients with organ confined disease and a high MIB 1 score had a lower 5-year disease-free survival rate (68 percent) than those with a low MIB 1 score (95 percent, p greater than 0.01). Conclusions Proliferative activity as measured by the Ki-67 proliferative antigen, MIB 1, appears to be a prognostic marker of recurrent prostate cancer after radical prostatectomy.