The association between CYP2D6 inhibition and recurrence in tamoxifen-treated patients is likely null or small.

The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genotype and recurrence of breast cancer. We used outcome and genotyping data from the large publicly available International Tamoxifen Pharmacogenomics Consortium (ITPC) dataset. Cox regression was used to compute the hazard ratios (HRs) for recurrence. CYP2C19 genotype data was available for 2 423 patients and the final sample cohort comprised 2 102 patients. CYP2C19*2 or *19 alleles did not influence DFS. For the CYP2C19*2 allele, the HR was 1.05 (CI 0.78–1.42) and 0.79 (CI 0.32–1.94) for hetero- and homozygote carriers, respectively. The corresponding HR for hetero- and homozygote carriers of the CYP2C19*17 allele were 1.02 (CI 0.71–1.46) and 0.57 (CI 0.26–1.24), respectively. Accounting for CYP2D6 genotype status did not change these estimates. We found no evidence to support a clinically meaningful role of CYP2C19 polymorphisms and response to tamoxifen in breast cancer patients and, consequently, CYP2C19 genotype status should not be included in clinical decisions on tamoxifen treatment.

A 35-year-old man with a history of blunt abdominal trauma and splenic rupture was diagnosed with an ampullary adenocarcinoma. At workup, a CT scan showed multiple intra-abdominal lesions similar to peritoneal carcinosis, and the patient was referred for palliative chemotherapy. On clinical suspicion, however, a biopsy was performed on an intra-abdominal lesion, establishing the diagnosis of abdominal splenosis. A radical pancreaticoduodenectomy ad modum Whipple was performed, followed by adjuvant chemotherapy with gemcitabine. At the 18-month follow-up, the patient was free from recurrent disease. We conclude that splenosis should be considered as a differential diagnosis of peritoneal metastases in cancer patients with a history of abdominal trauma and/or splenectomy. Other reports on splenosis in cancer patients and diagnostic workup are discussed.

These experimental findings suggest that a weak hepatic benefit of RSV treatment is seen in prevention of steatosis only.

Background Estrogen receptor (ER) expression predicts tamoxifen response, which halves the risk of breast cancer recurrence. We examined clinical factors associated with concordance between ER expression at diagnosis and centralized re-assay, and the association of concordance with breast cancer recurrence. Materials and Methods We used immunohistochemistry to assess ER expression on archived fixed, paraffin-embedded breast carcinoma tissue excised from women aged 35–69 years, diagnosed 1985–2001 in Jutland, Denmark. We calculated the percentage agreement, positive predictive value (PPV) and negative predictive value (NPV) of ER status at diagnosis and re-assay. We used logistic regression to investigate factors associated with concordance, and its association with recurrence (odds ratios (OR) and associated 95% confidence intervals (95%CI)). Results ER was re-assayed in 91% of patients (n=1530). Concordance was better in ER+ than ER− tumors (PPV=94% versus NPV=75%). Factors associated with concordance included menopausal status, tumor size, surgical procedure, diagnostic period, lymph node status and time to recurrence. ER+ women at diagnosis who re-assayed ER+ were less likely to have recurrent disease (OR=0.49, 95% CI=0.28, 0.86) than those who re-assayed ER−. In originally ER− women, concordance was not associated with recurrence (OR=0.97, 95% CI=0.66, 1.42). Conclusions Several clinical factors were associated with ER assay concordance. Some women were ineffectively treated with tamoxifen, or required but did not receive tamoxifen. We observed almost exactly the protective effect of endocrine therapy among tamoxifen-treated ER+ women whose tumors expressed the ER on re-assay, compared with those ER− on re-assay. Diagnostic pathology results for ER+ tumors appear a valid and useful resource for research studies. However, those for ER− tumors have lower validity. Study-specific considerations regarding the aims, diagnostic period, and consequences of including ER− patients with truly ER+ disease ought to be examined when using diagnostic pathology results for ER− tumors in research studies.