Toremifene in the treatment of breast cancer

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier (SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase III trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events and it has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.     

Ethnicity and outcome of young breast cancer patients in the United Kingdom: the POSH study

Background:

Black ethnic groups have a higher breast cancer mortality than Whites. American studies have identified variations in tumour biology and unequal health-care access as causative factors. We compared tumour pathology, treatment and outcomes in three ethnic groups in young breast cancer patients treated in the United Kingdom.

Methods:

Women aged ⩽40 years at breast cancer diagnosis were recruited to the POSH national cohort study (MREC: 00/06/69). Personal characteristics, tumour pathology and treatment data were collected at diagnosis. Follow-up data were collected annually. Overall survival (OS) and distant relapse-free survival (DRFS) were assessed using Kaplan–Meier curves, and multivariate analyses were performed using Cox regression.

Results:

Ethnicity data were available for 2915 patients including 2690 (91.0%) Whites, 118 (4.0%) Blacks and 87 (2.9%) Asians. Median tumour diameter at presentation was greater in Blacks than Whites (26.0 mm vs 22.0 mm, P=0.0103), and multifocal tumours were more frequent in both Blacks (43.4%) and Asians (37.0%) than Whites (28.9%). ER/PR/HER2-negative tumours were significantly more frequent in Blacks (26.1%) than Whites (18.6%, P=0.043). Use of chemotherapy was similarly high in all ethnic groups (89% B vs 88.6% W vs 89.7% A). A 5-year DRFS was significantly lower in Blacks than Asians (62.8% B vs 77.0% A, P=0.0473) or Whites (62.8 B% vs 77.0% W, P=0.0053) and a 5-year OS for Black patients, 71.1% (95% CI: 61.0–79.1%), was significantly lower than that of Whites (82.4%, 95% CI: 80.8–83.9%, W vs B: P=0.0160). In multivariate analysis, Black ethnicity had an effect on DRFS in oestrogen receptor (ER)-positive patients that is independent of body mass index, tumour size, grade or nodal status, HR: 1.60 (95% CI: 1.03–2.47, P=0.035).

Conclusion:

Despite equal access to health care, young Black women in the United Kingdom have a significantly poorer outcome than White patients. Black ethnicity is an independent risk factor for reduced DRFS particularly in ER-positive patients.     

Women on the liver transplantation waitlist are at increased risk of hospitalization compared to men

BACKGROUND Hospital admissions are common among patients with cirrhosis,but patient factors associated with hospitalization have not been well characterized.Given recent data suggesting increased liver transplant waitlist dropout among women,we hypothesized that women on the liver transplant waitlist would have increased rates of hospitalization compared with men.AIM To evaluate the role of gender on risk of hospitalization for patients on the liver transplant waitlist,in order to help explain gender disparities in waitlist outcomes.METHODS Patients listed for liver transplant at a single center in the United States were prospectively enrolled in the Functional Assessment in Liver Transplantation Study.Patients included in this retrospective analysis included those enrolled between March 2012 and December 2014 with at least 12 mo of follow up and without hepatocellular carcinoma.The primary and secondary outcomes were hospitalization and total inpatient days within 12 mo,respectively.Logistic and negative binomial regression associated baseline factors with outcomes.RESULTS Of the 392 patients,41%were female,with median(interquartile range)age 58 years(52-63)and model for end-stage liver disease 18(15-22).Within 12 mo,186(47%)patients were hospitalized≥1 time;48%were readmitted,with a median of 8(4-15)inpatient days.More women than men were hospitalized(54%vs 43%;P=0.03).In univariable analysis,female sex was associated with an increased risk of hospitalization[odds ratios(OR)1.6,95%confidence interval(CI)1.0-2.4;P=0.03],which remained significant on adjusted multivariable analysis(OR 1.6,95%CI:1.1-2.6;P=0.03).Female gender was also associated with an increased number of inpatient days within 12 mo in both univariable and multivariable regression.CONCLUSION Women with cirrhosis on the liver transplant waitlist have more hospitalizations and inpatient days in one year compared with men,suggesting that the experience of cirrhosis differs between men and women,despite similar baseline illness severity.Future studies should explore gender-specific vulnerabilities to help explain waitlist disparities.     

Common breast cancer susceptibility loci are associated with triple-negative breast cancer

Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer.     

An MRI-Driven Practice: a New Perspective on MRI for the Evaluation of Adenocarcinoma of the Head of the Pancreas

Objectives  

The purpose of the study was to describe the MRI-driven management of masses at the head of the pancreas.     

The rate of obstetric anal sphincter injuries in Finnish obstetric units as a patient safety indicator

Objective

To study whether there are significant differences in the rate of obstetric anal sphincter injuries (OASIS) between the different sized delivery units in Finland.

Study design

The study was performed as a population based registry study in Finland, including all births (294 725) between 2006 and 2010. All the Finnish delivery units (34) were categorized by the number of annual deliveries and the OASIS rate was then compared between the different sized delivery units using a logistic regression analysis adjusting for maternal age and parity. The Robson ten group classification was used for more accurate comparison.

Results

The OASIS rate was significantly elevated, both in the largest units with 5000 annual deliveries or more (OR 1.46, 95% CI 1.11–1.92) and in the smallest units with less than 500 annual deliveries (OR 1.33, 95% CI 1.22–1.45). In the Robson's group 1 (primiparous, single cephalic term pregnancy, spontaneous labour) the risk for OASIS was the highest in the largest units (OR 1.44, 95% CI 1.28–1.61) while in the Robson's group 3 (multiparous, single cephalic term pregnancy, spontaneous labour) the highest risk was found in the smallest units (OR 2.90, 95% CI 1.68–5.02).

Conclusions

There is significant inter-hospital variation in OASIS rates suggesting significant differences in obstetric practices. Robson's ten group classification should be used to enhance the inter-hospital comparison.