Harvey L. Bumpers

High prevalence of triple-negative tumors in an urban cancer center†

A disparate proportion of breast cancer deaths occur among young women, those of African‐American (AA) ancestry, and particularly young AA women. Estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor‐2 (HER‐2) are key clinically informative biomarkers. The triple‐negative (ER‐/PR‐/HER‐2‐) tumor subgroup is intrinsically resistant to treatment and portends a poor prognosis. Age, race, and socioeconomic status have been associated with triple‐negative tumors (TNT). In the current study, the authors investigated breast cancer subgroups among patients in an urban cancer center serving a multiracial, low socioeconomic population.

Predictive Capacity of Three Comorbidity Indices in Estimating Mortality After Surgery for Colon Cancer

PURPOSE Although, for patients with cancer, comorbidity can affect the timing of cancer detection, treatment, and prognosis, there is little information relating to the question of whether the choice of comorbidity index affects the results of studies. Therefore, to compare the association of comorbidity with mortality after surgery for colon cancer, this study evaluated the Adult Comorbidity Evaluation-27 (ACE-27), the National Institute on Aging (NIA) and National Cancer Institute (NCI) Comorbidity Index, and the Charlson Comorbidity Index (CCI). PATIENTS AND METHODS The study population consisted of colon cancer patients (N = 496) who underwent surgery at the University of Alabama at Birmingham Hospital from 1981 to 2002. Hazard ratios (HRs) with 95% CIs were obtained using the method of Cox proportional hazards for the three comorbidity indices in predicting overall and colon cancer-specific mortality. The point estimates obtained for comorbidity and other risk factors across the three models were compared. RESULTS For each index, the highest comorbidity burden was significantly associated with poorer overall survival (ACE-27: HR = 1.63; 95% CI, 1.24 to 2.15; NIA/NCI: HR = 1.83; 95% CI, 1.29 to 2.61; CCI: HR = 1.46; 95% CI, 1.14 to 1.88) as well as colon cancer-specific survival. For the other risk factors, there was little variation in the point estimates across the three models. CONCLUSION The results obtained from these three indices were strikingly similar. For patients with severe comorbidity, all three indices were statistically significant in predicting shorter survival after surgery for colon cancer.

Prognostic Significance of p53 Codon 72 Polymorphism Differs with Race in Colorectal Adenocarcinoma

Purpose: Several studies have examined the prognostic value of the codon 72 polymorphism of the p53 gene in colorectal adenocarcinoma, but none have addressed patient race/ethnicity. Therefore, this study assessed the prognostic value of this polymorphism in African American and Caucasian colorectal adenocarcinoma patients separately. Experimental Design: Colorectal adenocarcinomas from 137 African Americans and 236 non-Hispanic Caucasians were assessed for p53 mutations and genotyped for the codon 72 polymorphism. The phenotypes were correlated with p53 mutational status, clinicopathologic features, and patient survival using the χ2 test and Kaplan-Meier and Cox regression models. Results: The incidence of p53 mutations was similar in African American and Caucasian patients (50% versus 54%, respectively); however, the homozygous Pro72 allele frequency was higher in African Americans (17%) as compared with Caucasians (7%). In contrast, the homozygous Arg72 allele frequency was higher in Caucasians (36%) than in African Americans (19%). In African Americans but not Caucasians, the Pro/Pro phenotype significantly correlated with a higher incidence of missense p53 mutations and with nodal metastasis. African Americans, but not Caucasians, with the Pro/Pro phenotype had significantly higher mortality (log-rank P = 0.005 versus. P = 0.886) and risk of death due to colorectal adenocarcinoma (hazard ratio, 2.15; 95% confidence interval, 1.02-4.53 versus hazard ratio, 1.60; 95% confidence interval, 0.69-3.18) than those with the phenotype Arg/Arg or Arg/Pro. Conclusions: The higher frequency of the Pro/Pro phenotype of p53 in African American patients with colorectal adenocarcinoma is associated with an increased incidence of p53 mutations, with advanced tumor stage, and with short survival.

Effects of an outreach and internal navigation program on breast cancer diagnosis in an urban cancer center with a large African-American population

Compared with white women, African‐American (AA) women who are diagnosed with breast cancer experience an excess in mortality. To improve outcomes, the authors implemented community education and outreach initiatives in their cancer center, at affiliated primary care sites, and in the surrounding communities. They then assessed the effectiveness of these outreach initiatives and internal patient navigation on stage of diagnosis.

Pseudoangiomatous Stromal Hyperplasia (PASH) of the Breast: A Series of 24 Patients

Abstract:  Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. In 2005, only 109 cases had been reported since its initial description in 1986 by Vuitch et al. Our 24 cases represent one of the largest series to be reported from a single institution. We retrospectively reviewed data from 2004 to 2010 of patients diagnosed with PASH by surgical excision or image‐guided biopsy. All pathological specimens were reviewed by a single pathologist. The samples were stained for estrogen and progesterone receptors (ER and PR), CD34, and the lymphatic marker D2‐40. All but one of 24 (96%) patients presented with breast masses either on imaging or clinically. Fourteen of the 24 patients (58%) were diagnosed on surgical excision, 10 (42%) diagnosed with core needle biopsy, and five (20%) were diagnosed using both techniques. The tumors ranged in size from 0.3 cm to 7.0 cm. All women except two were premenopausal or perimenopausal at diagnosis. Nineteen samples were available for hormonal receptor staining and of these 18 of 19 (95%) were ER or PR positive. PASH was diagnosed in two men, a transgender male on hormones and the other with gynecomastia. The patients’ ages ranged from 18 to 86 years old. In addition to PASH other benign histopathological findings include stromal fibrosis and atypical ductal or lobular hyperplasia. Imaging revealed no distinguishing feature for PASH with benign histology. One patient had synchronous ductal carcinoma in‐situ (DCIS). Patients were treated with local excision or observation. This study suggests that PASH is primarily a diagnosis of premenopausal and perimenopausal women. Our series supports a hormonal basis for its development due to the positive staining for hormonal receptors. Management is conservative surgery for larger masses with careful observation being an option in patients not at high risk for breast cancer.

21-Gene recurrence scores: Racial differences in testing, scores, treatment, and outcome

African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)‐positive breast cancers. The 21‐gene recurrence score (RS) predicts recurrence in patients with ER‐positive/lymph node‐negative breast cancer according to RS score—low risk (RS, 0‐18), intermediate risk (RS, 19‐31), and high risk (RS, >31). The high‐risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome.

Laparoscopic cholecystectomy in patients with ventriculoperitoneal (VP) shunts

Increased intracranial pressure is often relieved by a ventriculoperitoneal shunt. The shunt has a one-way valve which can withstand pressures of 300 mmHg and prevent reflux of intraabdominal fluid. We have utilized laparoscopy for cholecystectomy in four patients with VP shunts. In all patients the peritoneal cavity was free of adhesions. When CO2 insufflation pressure was as high as 10–15 mmHg cerebrospinal fluid was still noted to flow from the end of the shunts. In three patients the entire procedure was performed laparoscopically. In the fourth patient the procedure was converted to an open cholecystectomy because of extensive inflammation surrounding a gangrenous gallbladder. Postoperatively the shunts remained intact and functional. There were no central nervous system sequelae. None of the shunts became infected. Elective laparoscopic cholecystectomy in patients with VP shunts can be done safely without a need for clamping or other manipulation of the shunt.

Characteristics and treatment modalities for African American women diagnosed with stage III breast cancer.

Stage III breast cancers account for about 6% to 7% of all invasive breast cancers diagnosed annually in the United States. In African American (AA) women, the incidence of stage III breast cancers is almost double that in Caucasian women. The aim of this study was to correlate age, receptor status, nuclear grade, and differences in treatment modalities for stage III breast cancer in an inner‐city hospital serving a large AA population.

Bax expression is a candidate prognostic and predictive marker of colorectal cancer

OBJECTIVE Since the anti-tumor activity of 5-fluorouracil (5-FU) is due to induction of apoptosis, we assessed the value of expression of key apoptotic molecules (Bax, Bcl-2 and p53) in predicting the efficacy of 5-FU therapy for colorectal adenocarcinomas (CRCs). METHODS Archival tissues of CRCs from 56 patients who received a complete regimen of 5-FU-based chemotherapy after surgery, and 56 patients matched for age, gender, ethnicity, tumor stage, tumor location, and tumor differentiation who had undergone only surgery (without any pre- or post-surgery therapy), were evaluated for immunophenotypic expression of Bax, Bcl-2, and p53. Also, these CRCs were evaluated for Bax mutations. The predictive capacity or prognostic value of these markers was assessed by estimating overall survival. RESULTS The majority of low Bax expressing CRCs have exhibited mutations at the G (8) tract. There was no significant difference in overall survival rates between the categories of surgery alone and 5-FU-treated patients. However, a better survival was observed for patients who received chemotherapy when their CRCs had low Bax/Bcl2 ratio (HR, 1.55; 95% CI: 1.46-31.00). Patients who received surgery alone and whose CRCs lacked Bax expression had 5.33 times higher mortality than those with high Bax expression (95% CI: 1.78-15.94), when controlled for tumor stage and other confounders. Bcl-2 and nuclear p53 accumulation had no predictive value in either patient group. CONCLUSION These findings are the first to demonstrate that high Bax expression is a good prognosticator for patients who underwent surgery alone, and that patient with low Bax/Bcl-2 expression ratio benefit from 5-FU-based adjuvant therapies.

Development and progression of colorectal neoplasia

A variety of genetic and molecular alterations underlie the development and progression of colorectal neoplasia (CRN). Most of these cancers arise sporadically due to multiple somatic mutations and genetic instability. Genetic instability includes chromosomal instability (CIN) and microsatellite instability (MSI), which is observed in most hereditary non-polyposis colon cancers (HNPCCs) and accounts for a small proportion of sporadic CRN. Although many biomarkers have been used in the diagnosis and prediction of the clinical outcomes of CRNs, no single marker has established value. New markers and genes associated with the development and progression of CRNs are being discovered at an accelerated rate. CRN is a heterogeneous disease, especially with respect to the anatomic location of the tumor, race/ethnicity differences, and genetic and dietary interactions that influence its development and progression and act as confounders. Hence, efforts related to biomarker discovery should focus on identification of individual differences based on tumor stage, tumor anatomic location, and race/ethnicity; on the discovery of molecules (genes, mRNA transcripts, and proteins) relevant to these differences; and on development of therapeutic approaches to target these molecules in developing personalized medicine. Such strategies have the potential of reducing the personal and socio-economic burden of CRNs. Here, we systematically review molecular and other pathologic features as they relate to the development, early detection, diagnosis, prognosis, progression, and prevention of CRNs, especially colorectal cancers (CRCs).