Early-stage gallbladder cancer in the Surveillance, Epidemiology, and End Results database: effect of extended surgical resection.

HYPOTHESIS: Extended surgical resection (ESR) may improve survival in patients with early-stage primary gallbladder cancer. DESIGN: Retrospective analysis of findings in the Surveillance, Epidemiology, and End Results (SEER) database. SETTING: Academic research. PATIENTS: Individuals with potentially surgically curable gallbladder cancer (Tis, T1, or T2) who underwent a surgical procedure. MAIN OUTCOME MEASURES: Overall survival, number of lymph nodes (LNs) excised, and results of simple cholecystectomy vs ESR. RESULTS: We identified 3209 patients with early-stage gallbladder cancer (11.7% Tis, 30.1% T1, and 58.2% T2). On multivariate analysis, decreased survival was noted among patients older than 60 years (hazard ratio, 1.57; 95% confidence interval, 1.30-1.90), among patients with more advanced cancer (1.99; 1.46-2.70 for T1; 3.29; 2.45-4.43 for T2), and among patients with disease-positive LNs (1.65; 1.39-1.95 for regional; 2.58; 1.54-4.34 for distant) (P < .001 for all), while increased survival was observed among female patients (0.82; 0.70-0.96; P = .02) and among patients undergoing ESR (0.59; 0.45-0.78; P < .001). The survival advantage of ESR was seen only in patients with T2 lesions (0.49; 0.35-0.68; P < .001). Lymph node excision data were available for a subset of 2507 patients, of whom 68.2% had no LN excised, 28.2% had 1 to 4 LNs excised, and 3.6% had 5 or more LNs excised. On multivariate analysis, patients with 1 to 4 LNs excised had a survival benefit over those with no LN excised (HR, 0.55; 95% CI, 0.46-0.66; P < .001), and patients with 5 or more LNs excised had a survival benefit over patients with 1 to 4 LNs removed (0.63; 0.40-0.96; P = .03). Lymph node excision improved survival in patients with T2 lesions (0.42; 0.33-0.53; P < .001 for patients with 1-4 LNs excised). CONCLUSION: Extended surgical resection, LN excision, or both may improve survival in certain patients with incidentally discovered gallbladder cancer.

Surgical treatment for women with breast cancer: do randomized clinical trials represent current medical practices?

Randomized clinical trials have not shown survival differences between breast cancer patients who undergo breast-conserving surgery and those who undergo modified radical mastectomy (MRM). Recent studies however, have suggested that these randomized clinical trials findings may not be representative of the entire population or the nature of current patient care. A retrospective analysis of female invasive breast cancer patients who underwent surgery in the Surveillance, Epidemiology, and End Results database (1990-2003) was performed. Survival was compared amongst women who underwent partial mastectomy, partial mastectomy plus radiation (PMR), or MRM. Cox proportional hazards regressions were used to investigate the impact of method of treatment upon survival, after adjusting for patient and tumor characteristics. A total of 218,043 patients, mean age 62 years, were identified. MRM accounted for 51.5 per cent of the study population whereas PMR accounted for 34.9 per cent. On multivariate analyses, significant improvement was observed in patient survival associated with PMR when compared with MRM patients (hazard ratio = 0.71, 95% confidence interval = 0.67-0.74, P < 0.001). This population-based study suggests that there is a survival benefit for women undergoing PMR in the treatment of breast cancer.

Clinical significance of p53 and bcl-2 protein coexpression phenotypes in molecular breast cancer subtypes of pre-menopausal and post-menopausal African-American women.

With the current classification of breast carcinoma into molecular subtypes with distinct prognosis and response to therapy, we sort to assess the clinical significance of p53 and bcl-2 coexpression phenotypes in invasive breast tumors and correlate this to the different molecular breast cancer subtypes in African-American women. We performed a retrospective analysis of data on p53 and bcl-2 expression. Results were correlated to molecular breast cancer subtypes, and clinicopathologic variables of prognostic significance. Our study sample included all African-American women diagnosed with breast cancer from 1998 to 2005. Twenty-seven (27.6%) per cent of cases in our study sample over-expressed p53, whereas 69.3 per cent over-expressed bcl-2 protein. A significant inverse correlation was observed between expression of p53 and bcl-2. Combined analysis of p53 and bcl-2 showed that 53.2 per cent of the tumors displayed p53(-)bcl-2(+) phenotype which was significantly associated with the luminal A subtype, whereas 11.6 per cent displayed the p53(+)bcl-2(-) phenotype which was significantly associated with the basal cell-like and Her-2/neu. Neither p53 expression nor bcl-2 expression individually or in combination were of independent prognostic significance. p53(+)bcl-2(-) phenotype is significantly correlated with the basal cell-like subtype and may be associated with the biologic aggressiveness of this cohort of molecular breast cancer.

Treatment and survival outcome for molecular breast cancer subtypes in black women.

OBJECTIVE: To analyze whether the local-regional surgical treatments (breast-conserving therapy, mastectomy) resulted in different overall survival, distant metastasis-free survival, and locoregional recurrence-free survival rates for the various molecular breast cancer subtypes. SUMMARY BACKGROUND DATA: Molecular gene expression profiling has been proposed as a new classification and prognostication system for breast cancer. Current recommendation for local-regional treatment of breast cancer is based on traditional clinicopathologic variables. METHODS: Retrospective analysis of 372 breast cancer cases with assessable immunohistochemical data for ER, PR, and Her-2/neu receptor status, diagnosed from 1998 to 2005. Molecular subtypes analyzed were luminal A, luminal B, basal like, and Her-2/neu. RESULTS: No substantial difference was noted in overall survival, and locoregional recurrence rate between the local-regional treatment modalities as a function of the molecular breast cancer subtypes. The basal cell-like subtype was an independent predictor of a poorer overall survival (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.28-4.97, P < 0.01) and a shorter distant metastasis-free survival time (HR = 3.61, 95% CI 1.27-10.2, P < 0.01), and showed a tendency toward statistical significance as an independent predictor of locoregional recurrence (HR = 3.57, 95% CI 0.93-13.6, P = 0.06). CONCLUSIONS: The basal cell-like subtype is associated with a worse prognosis, a higher incidence of distant metastasis, and may be more prone to local recurrence when managed with breast-conserving therapy.

Basal cell-like (triple-negative) breast cancer, a predictor of distant metastasis in African American women.

BACKGROUND: The aim of this study was to evaluate the prognostic significance of the basal cell-like molecular breast cancer subtype with respect to locoregional recurrence and distant metastasis in African American women treated for breast cancer. METHODS: A retrospective analysis was performed of the tumor registry database for all African American women diagnosed and treated for breast cancer from 1998 to 2005 who had assessable data for all 3 markers: estrogen, progesterone, and Her-2/neu. RESULTS: A total of 372 patients were included in our study sample. Of these, 22 (6.1%) had locoregional recurrence, 35 (9.8%) had distant metastasis, and 301 (84.1%) had no evidence of breast tumor recurrence. The median follow-up time was 36 months. Compared with the other molecular subtypes the basal cell-like subtype showed a statistically significant association to distant metastasis: 15 (42.9%) vs 13 (37.1%), 4 (11.4%), and 3 (8.6%) (P < .001), respectively, for luminal A, Her-2/neu, and luminal B subtypes. The basal cell-like subtype was an independent predictor of distant metastasis (odds ratio, 5.8; 95% confidence interval, 1.5-22.0, P = .009). The molecular subtypes showed no statistically significant difference with respect to locoregional treatment administered and tumor stage at time of diagnosis. CONCLUSIONS: The basal cell-like molecular breast cancer subtype is an independent predictor of distant metastasis in African American women.

Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women: age-specific prevalence and survival.

BACKGROUND: Breast cancer is currently regarded as a heterogeneous disease classified into various molecular subtypes using gene expression analysis. These molecular subtypes include: basal cell-like, Her-2/neu, luminal A, and luminal B. OBJECTIVES: To analyze the prevalence and clinicopathologic associations for molecular breast cancer subtypes in premenopausal and postmenopausal African-American women. DESIGN: A retrospective analysis of all African-American women diagnosed with breast cancer from 1998 to 2005, who had assessable data for ER, PR, and Her-2/neu status. Molecular subtype classification was done based on immunohistochemical surrogates for ER, PR, and Her-2/neu status obtained from Howard University tumor registry for each patient. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-), and Her-2/neu (ER-, PR-, and HER2+). OUTCOME MEASURES: We analyzed the prevalence of molecular breast cancer subtypes in a population of African-American women and determined their associations with patient demographics and clinicopathologic variables: node status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival. RESULTS: The luminal A subtype was the most prevalent in our study sample (55.4%) compared with (11.8%) luminal B, (21.2%) basal cell-like, and (11.6%) Her-2/neu subtypes. The molecular subtypes did not differ by menopausal status. However, when stratified into age-specific groups, the basal cell-like subtype (57.1%) was the most prevalent in the age group <35 y compared with luminal A, luminal B, and Her-2/neu subtypes at 25.0%, 14.3%, and 3.6%, respectively. The basal cell-like subtype also showed an age-specific bimodal distribution with a peak in the <35 y and 51 to 65 y age groups. The basal cell-like and the Her-2/neu subtypes showed an increased association with clinicopathologic variables portending a more aggressive clinical course when compared with luminal A subtype. A paradoxical inverse relationship between the expression of p53 and Bcl-2 protooncoprotein was noted in the molecular subtypes. Breast cancer-specific survival differed significantly among the molecular subtypes (P < 0.04), with the basal cell-like and Her-2/neu subtypes having the poorest outcome. CONCLUSIONS: The high prevalence of the basal cell-like subtype in the young premenopausal African-American women aged <35 y could be a contributory factor to the poorer prognosis of breast cancer observed in this cohort of patients.

Molecular breast cancer subtypes in premenopausal African-American women, tumor biologic factors and clinical outcome.

INTRODUCTION: Breast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women. METHODS: A retrospective analysis of Howard University Hospital tumor registry, for all premenopausal African-American women aged less than 50 years, diagnosed with breast cancer from 1998-2005, was performed. RESULTS: The luminal A subtype was the most prevalent (50.0%), vs basal-cell-like (23.2%), luminal B (14.1%), and HER-2/neu (12.7%). However when stratified by age groups, results showed that in the age group <35 years the basal-cell-like subtype was the most prevalent (55.6%), vs 25.9%, 14.8%, and 5.6% for luminal A, luminal B, and HER-2/neu subtypes, respectively (P < .000). P53 mutation was more prevalent in the basal-cell-like subtype compared to luminal A (48.0% vs 18.6%, P < .01). The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000). Though not statistically significant, HER-2/neu and basal-cell-like subtypes had the shortest survival time (P < .31). CONCLUSION: The high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women.

The Southern Surgical Association History of Medicine Scholarship presentation: Dr. Charles Drew, a surgical pioneer.

When one considers the circumstances of his birth, the barriers that he had to overcome, and his abbreviated life span (<46 years), a strong case can be made that Charles Drew, MD, CM, MDSc, was one of the most accomplished surgeons of the 20th Century; yet many practitioners and instructors of the surgical sciences know little or nothing about him. There are others who have heard of him and still harbor popular misconceptions about the circumstances of his death that have been perpetuated by several media outlets. The Southern Surgical Association promotes a substantially more inclusive brand of surgical fellowship than it did during the lifetime of Dr. Drew. We believe that the membership would greatly appreciate knowing some of the details of Dr. Drew's life, particularly his major scientific contributions and his commitment to excellence in patient care, and in the training of young surgeons.

Identification of MMP-1 as a putative breast cancer predictive marker by global gene expression analysis.

Breast cancer is the second leading cause of cancer death for women in the United States. In 2005, about 215,000 cases of invasive breast cancer (IBC) and 50,000 cases of ductal carcinoma in situ will be diagnosed and 40,000 women will die of IBC in the US. Yet there is presently no molecular marker that can be used to detect a precancerous state or identify which premalignant lesions will develop into invasive breast cancer. Here we report the gene expression analysis of atypical ductal hyperplastic tissues from patients with and without a history of breast cancer. We identify MMP-1 as a candidate marker that may be useful for identification of breast lesions that can develop into cancer.

Interactions between genetic and reproductive factors in breast cancer risk in a population-based sample of African-American families.

Incidence of breast cancer (BC) varies among ethnic groups, with higher rates in white than in African-American women. Until now, most epidemiological and genetic studies have been carried out in white women. To investigate whether interactions between genetic and reproductive risk factors may explain part of the ethnic disparity in BC incidence, a genetic epidemiology study was conducted, between 1989 and 1994, at the Howard University Cancer Center (Washington, DC), which led to the recruitment of 245 African-American families. Segregation analysis of BC was performed by use of the class D regressive logistic model that allows for censored data to account for a variable age of onset of disease, as implemented in the REGRESS program. Segregation analysis of BC was consistent with a putative dominant gene effect (P < 0.000001) and residual sister-dependence (P < 0.0001). This putative gene was found to interact significantly with age at menarche (P = 0.048), and an interaction with a history of spontaneous abortions was suggested (P = 0.08). A late age at menarche increased BC risk in gene carriers but had a protective effect in non-gene carriers. A history of spontaneous abortions had a protective effect in gene carriers and increased BC risk in non-gene carriers. Our findings agree partially with a similar analysis of French families showing a significant gene x parity interaction and a suggestive gene x age at menarche interaction. Investigating gene x risk factor interactions in different populations may have important implications for further biological investigations and for BC risk assessment.