Is mammographic breast density a breast cancer risk factor in women with BRCA mutations?

PURPOSE: Increased mammographic breast density is well recognized as a breast cancer risk factor in the general population. However, it is unclear whether it is a risk factor in women with BRCA mutations. We present the results of a nested case-control screening study investigating the relationship between breast density and breast cancer incidence in this population. PATIENTS AND METHODS: Women ages 25 to 65 years with known BRCA mutations were enrolled onto a single-center, high-risk breast cancer screening program. Using a computer-aided technique (Cumulus), quantitative percentage density (PD) was measured for each participant on her baseline mammogram by a single, blinded observer. RESULTS: Between November 1997 and March 2008, 462 women (mean age, 44 years; 245 BRCA1 and 217 BRCA2) were screened and 50 breast cancers were diagnosed (38 invasive, 12 ductal carcinoma in situ [DCIS]). Density was not measured in 40 women of whom four developed cancer (three invasive, one DCIS). Mean PD (+/- standard deviation [SD]) for 376 women who did not develop breast cancer was 34% (23) compared with 31% (21) for 46 women with cancer (P = .51). Logistic regression model of breast cancer incidence and PD revealed an odds ratio of 0.99 (+/- 0.01 SD) for a one-unit increase in PD (P = .44). Results remained nonsignificant in multivariate analysis, as well as when women with pure DCIS were excluded. CONCLUSION: Increased mammographic breast density is not associated with higher breast cancer incidence in women with BRCA mutations. On the basis of these findings, density should not be considered a factor for these women in decision making regarding prophylactic surgery or chemoprevention.

Do patients' comfort levels and attitudes regarding medical student involvement vary across specialties?

BACKGROUND: Studies on patient comfort with medical student involvement have been conducted within several specialties and have consistently reported positive results. However, it is unknown whether the intrinsic differences between specialties may influence the degree to which patients are comfortable with student involvement in their care. AIM: This is the first study to investigate whether patient comfort varies across specialties. METHODS: A total of 625 patients were surveyed in teaching clinics in Family Medicine, Obstetrics/Gynaecology, Urology, General Surgery, and Paediatrics. Seven patient attitudes and patients' comfort levels based on student gender, level of training, and type of clinical involvement were assessed. RESULTS: Patients in all specialties shared similar comfort levels and attitudes regarding medical student involvement for the majority of parameters assessed, suggesting that findings in this area may be generalised between specialties. Most of the inter-specialty variation found pertained to patient preference for student gender and the genitourinary specialties. CONCLUSION: As there are numerous specialties that have never undergone a similar investigation of their patients, this study has important implications for medical educators in those specialties by supporting their ability to apply the results and recommendations of studies conducted in other specialties to their own.

Effect of copper on the cytotoxicity of phenanthrene and 9,10-phenanthrenequinone to the human placental cell line, JEG-3.

The trophoblast cell line, JEG-3, was used to study the cytotoxicity of phenanthrene, 9,10-phenanthrenequinone (PHEQ), anthracene, and 9,10-anthracenedione alone and with copper. The endpoints were the capacity of cultures to reduce alamar Blue (AB), a measure of energy metabolism, and to convert carboxyfluorescein diacetate acetoxymethyl ester (CFDA AM) to carboxyfluorescein, an indication of membrane integrity. Only PHEQ elicited a cytotoxic response. PHEQ caused a concentration-dependent decline in AB but not in CFDA AM readings, suggesting an impairment to energy metabolism. In the presence of copper, PHEQ concentration-response curves were shifted to the left for AB and were obtained with CFDA AM. The Cu/PHEQ synergy is attributed to an increase in redox cycling and production of reactive oxygen species (ROS), which overwhelm antioxidant defenses, damaging energy metabolism first and then membrane integrity. The impermeable copper chelator, bathocuproine, reduced the PHEQ/copper interaction, but the permeable chelator, neocuproine, and copper together were cytotoxic.

Pelvic chemoradiotherapy after chemotherapy for metastatic bladder cancer.

OBJECTIVE: Consolidative radiotherapy has improved local control in other tumors with high local recurrence rates but has not been well studied in urothelial cancer. We hypothesized that pelvic chemoradiotherapy (PCRT) given after systemic chemotherapy for metastatic bladder cancer (MTCC) might alter the pattern of disease recurrence, and reduce the complications and morbidity of intrapelvic disease relapse. A 74% locoregional relapse rate has been observed in MTCC patients with intrapelvic nodal disease after response to chemotherapy. To explore this hypothesis further, we performed a retrospective analysis and report the efficacy, toxicity and pattern of failure with this approach. MATERIALS AND METHODS: Patients treated for MTCC who received consolidative PCRT following at least a partial response to systemic chemotherapy were identified and their charts reviewed for pelvic relapse, disease progression, survival, and toxicity. RESULTS: Twelve patients were identified and median follow-up was 15.6 months. Nine patients developed progressive disease and died, and median survival was 15.6 months. Three patients had pelvic progression (pelvic failure rate 25%). Median time to pelvic failure was 12.8 months. At last follow-up, three patients were alive and disease-free. No life-threatening toxicities were observed. The most common acute non-hematological toxicities were diarrhea and nausea. CONCLUSIONS: These data support a hypothesis that consolidative PCRT following chemotherapy in MTCC patients with systemic disease control may be feasible and efficacious for improving pelvic disease control. This intervention should be considered for further study in prospective controlled clinical trials.