First-line all-oral NORCAP (vinorelbine/capecitabine) might be alternative to taxane-based chemotherapy for HER2-negative metastatic breast cancer

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Clinical outcomes linked to expression of gene subsets for protein hormones and their cognate receptors from LCM-procured breast carcinoma cells

Abstract

Purpose

Certain peptide hormones and/or their cognate receptors influencing normal cellular pathways also have been detected in breast cancers. The hypothesis is that gene subsets of these regulatory molecules predict risk of breast carcinoma recurrence in patients with primary disease.

Methods

Gene expression levels of 61 hormones and 81 receptors were determined by microarray with LCM-procured carcinoma cells of 247 de-identified biopsies. Univariable and multivariable Cox regressions were determined using expression levels of each hormone/receptor gene, individually or as a pair.

Results

Molecular signatures for ER+/PR+, ER−/PR−, and ER− carcinoma cells deciphered by LASSO were externally validated at HRs (CI) of 2.8 (1.84–4.4), 1.53 (1.01–2.3), and 1.72 (1.15–2.56), respectively. Using LCM-procured breast carcinoma cells, a 16-gene molecular signature was derived for ER+/PR+ biopsies, whereas a 10-gene signature was deciphered for ER−/PR− cancers. Four genes, POMC, CALCR, AVPR1A, and GH1, of this 10-gene signature were identified in a 6-gene molecular signature for ER− specimens.

Conclusions

Applying these signatures, Kaplan–Meier plots definitively identified a cohort of patients with either ER−/PR− or ER− carcinomas that exhibited low risk of recurrence. In contrast, the ER+/PR+ signature identified a cohort of patients with high risk of breast cancer recurrence. Each of the three molecular signatures predicted clinical outcomes of breast cancer patients with greater accuracy than observed with either single-gene analysis or by ER/PR protein content alone. Collectively, our results suggest that gene expression profiles of breast carcinomas with suspected poor prognosis (ER−/PR−) have identified a subset of patients with decreased risk of recurrence.

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Acute and late toxicities of pirarubicin in the treatment of childhood acute lymphoblastic leukemia: results from a clinical trial by the Japan Association of Childhood Leukemia Study

Abstract

Background

Anthracyclines are used to treat childhood acute lymphoblastic leukemia (ALL). Even when administered at low doses, these agents are reported to cause progressive cardiac dysfunction. We conducted a clinical trial comparing the toxicities of two anthracyclines, pirarubicin (THP) and daunorubicin (DNR), in the treatment of childhood ALL. The results from our study that relate to acute and late toxicities are reported here.

Methods

276 children with B-ALL were enrolled in the trial from April 1997 to March 2002 and were randomly assigned to receive a regimen including either THP (25 mg/m² × 11) or DNR (30 mg/m² × 11). Acute toxicity was prospectively assessed based on the National Cancer Institute Common Toxicity Criteria. Acute hematological toxicity was also examined via some parameters. Patients with event-free survival of >5 years were retrospectively surveyed for cardiac function at 5 and 10 years and at the most recent assessment more than 10 years from the onset of ALL.

Results

Acute hematological toxicity in the early phase was more significant in the THP arm. Based on ultrasound cardiography, cardiac function was impaired in both groups during the follow-up period, but there was no significant difference between the groups except for a greater decline in fractional shortening on ultrasound cardiography in the DNR arm.

Conclusions

While acute hematological toxicity was more significant in the THP arm, THP also appeared to be less cardiotoxic. However, the evaluation of late cardiotoxicity was limited because only a few subjects were followed beyond 10 years after ALL onset. Considering that the THP regimen produced an EFS rate comparable with that of the DNR regimen, the efficacy and toxicity of THP at reduced doses should be studied in order to identify potentially safer regimens.

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NCI outlines tobacco control research priorities

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Issue Information – TOC – Masthead

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Most parents would support school HPV vaccine requirements if offered opt-out provisions

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Combining ipilimumab with local treatments for melanoma may improve survival

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