The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1

CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.     

Semi-Quantitative and Qualitative Assessment of Breast Ultrasound Elastography in Differentiating Between Malignant and Benign Lesions

The purpose of this study was to evaluate the diagnostic value of qualitative and semi-quantitative assessment of ultrasound elastography in differentiating between benign and malignant breast lesions. This prospective study was conducted in two tertiary medical centers. Consecutive B-mode ultrasound and real-time elastographic images were obtained for 67 malignant and 101 benign breast lesions in 168 women. Four experienced radiologists analyzed B-mode ultrasound alone and B-mode ultrasound combined with elastography independently. Conventional ultrasound findings were classified according to the American College of Radiology Breast Imaging Reporting and Data System classification. The elastographic assessment was based on qualitative and semi-quantitative parameters (i.e., strain pattern, width ratio, strain ratio). The sensitivity and specificity of combined elastography and conventional ultrasound were significantly higher than that of conventional ultrasound alone. The sensitivity, specificity, positive predictive value and negative predictive value was 97%, 61.4%, 62.5% and 96.8%, respectively, for conventional ultrasound and 100%, 93%, 99% and 90%, respectively, for combined technique. The semi-quantitative assessment with strain ratio and width ratio in elastography were the most useful parameters in differentiating between benign and malignant breast lesions. Cut-off point values for width ratio of more than 1.1 and strain ratio of more than 5.6 showed a high predictive value of malignancy with specificities of 84% and 76%, respectively (p < 0.001). This combined technique also had the best results in detecting carcinoma and could reduce the need of unnecessary biopsy for benign lesions with indeterminate or equivocal features.     

Isolated late chest wall recurrence after mastectomy for breast cancer

An isolated late chest wall recurrence after mastectomy for breast cancer is rare. We present a case of a lady with a T2N1M0 right breast cancer who developed an isolated local recurrence on the chest wall 11 years after mastectomy. Staging investigations excluded distant metastases. She underwent an excisional biopsy and was started on an aromatase inhibitor. Radiotherapy was given to the chest wall followed by a boost to the site of excision. Although most chest wall recurrences fare poorly, a favourable subgroup can be identified and should be treated aggressively in a multidisciplinary approach.