A case report of the sustained and rapid response of bevacizumab in a TP53-positive breast cancer and liver metastatic patient through personalized medicine.

HER2-positive metastatic breast cancer is much less frequent than other subgroups of breast cancer. Treatment options for this cancer are mostly limited to systemic chemotherapy, which leads to moderate improvements. Targeted therapy against malignant breast cancer requires the identification of reliable biomarkers for personalized medicine to obtain the maximum benefit of this therapy. Any mutations in the TP53 signaling pathway can be considered as a significant causative factor of breast cancer, for which the identification of target genes plays an important role in selecting the appropriate treatment. The use of personalized gene expression profiling could be valuable to find the direct target of the treatment in this case. The present study assessed the genetic profile of an HER2-positive metastatic breast cancer patient (with a liver metastasis) and figured out a complete and sustained response to bevacizumab. According to the results of next-generation sequencing (NGS) analysis, the patient's genetic profile showed an increased expression of p4EBP1 and PTEN and the activation of the mTOR signaling pathway with a mutation in the TP53 gene. Based on the common treatment of similar profiling, we administrated bevacizumab/Taxol/Gemzar chemotherapy up to six courses. Accordingly, as the response to treatment was revealed by reducing the volume of the liver metastasis from 4 to 1.4 cm, metastasectomy was performed as a complementary treatment. Hence, personalized gene expression profiling not only is useful for targeted therapy but also could be recommended to avoid prescription of non-responsive drugs.

Concurrent Chemo- Radiobrachytherapy with Cisplatin and Medium Dose Rate Intra- Cavitary Brachytherapy for Locally Advanced Uterine Cervical Cancer

Objective: Cervical carcinoma is the third most common gynecologic cancer, after ovarian and uterine cancers in Iran. The aim of this study was to evaluate the efficacy (response rate) and toxicity of adding Medium Dose Rate (MDR) brachytherapy with concurrent chemotherapy to External Beam Radiotherapy (EBRT) for the treatment of locally advanced uterine cervical carcinoma. Methods: This phase I-II study was conducted in 2007-2008 at the cancer institute, Tehran University of Medical Sciences. Patients were treated with pelvic EBRT (50 Gy in 25 Fraction) with concomitant chemotherapy to obtain tumor shrinkage and permit optimal intra-cavitary placement. One week after the completion of EBRT, patients were treated by 12 Gy MDR Intra-cavitary brachytherapy for two periods of one day with a one week interval and concomitant platinum based chemotherapy. Response rate was evaluated by gynecologic physical examination and pelvic MRI +- GD within three months of treatment. Acute and late toxicity were assessed using Radiation Therapy Oncology Group criteria. Results: A total of 33 patients with locally advanced cervical cancer were treated according to the above described treatment protocol. The patients mean age was 53.2 (range 31­78) years. Three months after the completion of treatment, the complete clinical, pathologic and radiologic response rate according to WHO-criteria was 81.8% (27 patients). Six cases had a partial response or stable disease. After 48 months, average disease free survival periods were 45.1, 23.0, 33.4 and 8 months for stage IIB, IIIA, IIIB and: IVA lesions (according to The International Federation of Gynecology and Obstetrics staging system). The most frequently observed side effects were leukopenia, anemia, proctitis, cystitis, nausea and vomiting (mostly grade 1 and 2). Conclusion: Concomitant brachytherapy and chemotherapy with platinum compounds can be well tolerated and is effective in the treatment of locally advanced cervical cancer.