A targeted approach to genetic counseling in breast cancer patients: the experience of an Italian local project.

AIMS AND BACKGROUND: Patients with hereditary breast cancer (BC) may benefit from genetic counseling and testing for detection of causative mutations, definition of therapeutic and preventive strategies, and identification of at-risk relatives. Italy has few oncogenetic centers and genetic evaluation of all patients with BC is not feasible. Moreover, lack of uniformity in the selection of patients generates inappropriate referral to the geneticist. We designed a model that may represent a reproducible way to select patients at risk for hereditary BC, with the aims of rationalizing access to genetic centers and improving clinical management and surveillance. METHODS: The genetic unit of a Cancer Center and the Departments of Oncology from 2 public Hospitals in Milan were involved in the project. After training sessions at the genetic unit, operators from the 2 hospitals evaluated all patients with BC attending a first oncologic visit, through a specific interview. Patients considered at risk of hereditary BC attended counseling at the genetic unit. RESULTS: Of 419 patients, 61 (14.5%) were eligible for genetic counseling after the interview. Of these, 46 (10.9%) strictly met testing criteria. Overall, 52 (12.4%) patients underwent genetic counseling and 47 were tested for BRCA1/BRCA2 mutation. After genetic test results, the available options for treatment/surveillance were discussed by a multidisciplinary team, according to the level of genetic risk. CONCLUSIONS: It is possible to improve the process of referring patients with suspected hereditary BC for genetic risk assessment. The application of clinical screening reduced the genetics unit's workload and enabled optimization of time and resources.

Prospective, mono-institutional study of the impact of a systematic prevention program on incidence and outcome of osteonecrosis of the jaw in patients treated with bisphosphonates for bone metastases.

The aim of our study was to investigate the occurrence of osteonecrosis of the jaw (ONJ) after implementation of dental preventive measures before starting bisphosphonates (BPs) therapy and during treatment. All consecutive patients with bone lesions eligible for BPs treatment were prospectively evaluated. Before starting BPs, each patient underwent a strict dental preventive program with a specialized odontoiatric team. The odontoiatric evaluation identified patients with oral pathologies or inadequate oral hygiene and provided a dental preventive treatment. From April 2007 to April 2012, 254 patients were enrolled. After excluding patients due to previous BPs treatment, 212 patients with a mean age of 74 years (range 37-95) were included. On average, patients received 9.7 treatment cycles (range 1-48). No ONJ was recorded (0.0 %; 95 % confidence interval [CI] 0.0-1.4). Comparing this risk with that observed in a previous cohort who did not receive dental prevention (16/186, 8.6 %; 95 % CI 4.2-15.3 %), we observed clear efficacy in preventing ONJ (relative risk reduction: 100 %, 95 % CI 86-100 %, P < 0.0001). We developed a strict three-step prevention program that is able to decrease ONJ incidence and the need for destructive surgery with permanent sequelae. We demonstrated that ONJ could be effectively prevented. We recommend a mandatory preventive program involving a multidisciplinary team for all patients starting BPs.

Efficacy of biological agents in metastatic triple-negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) represents 15% of invasive breast cancers. Prognosis is poor, and there is no specific target therapy but biological agents combined with chemotherapy may be effective. To assess the role of biological agents in metastatic triple-negative breast cancer we performed a systematic review of phase III randomized controlled trials published from January 2006 to February 2013 and presentations at ESMO, ASCO, and SABCS congresses in 2010-2012. We consulted PubMed and ClinicalTrials.gov. Only studies comparing biological agents and chemotherapy versus chemotherapy alone were considered. Relevant statistical variables were log of the hazard ratio and relative variance for progression-free survival (PFS) and overall survival (OS). Of 353 PubMed publications and 229 studies registered on ClinicalTrials.gov, 10 trials were selected and 5293 patients were analyzed: 1546 had mTNBC. Biological agents considered were bevacizumab, sunitinib, sorafenib, lapatinib, iniparib and cetuximab. In addition, a meta analysis of the four studies containing bevacizumab was performed and it showed a PFS improvement with a relative risk reduction of 35% (95% CI: 25-43%). No effect on OS was observed. No PFS and OS benefit was detected with the other agents. No improvement of OS was detected in patients treated with biological agents plus chemotherapy, while a significant PFS improvement was observed only for bevacizumab and cetuximab. The overall impact of these agents on patient survival was not as great as expected, probably because the molecular basis of this illness needs to be better understood so that treatment can be more appropriately tailored.

Eribulin in cutaneous breast cancer metastasis treatment: clinical activity and symptom control.

AIM: This observational study evaluated the behavior and outcome of cutaneous breast cancer metastasis treated with eribulin. PATIENTS & METHODS: From November 2012 to January 2013, oncologists completed a database with patient, tumor and treatment characteristics from 14 Italian cancer centers. Skin lesions were assessed by Response Evaluation Criteria In Solid Tumors and cutaneous symptoms by present/absent criteria. RESULTS: A total of 23 metastatic breast cancer patients with skin metastasis who were treated with eribulin were analyzed. After treatment, 43% of patients exhibited a partial response, 35% stable disease and 22% progressive disease. Regarding only the skin response, 26% obtained a complete response, 22% a partial response, 39% stable disease and 13% progressive disease. We found an improvement in symptoms, infiltration and ulceration. With a median follow-up of 6 months, median progression-free survival was 4.3 months and median overall survival was 9.1 months. CONCLUSION: The response rate of skin metastasis to eribulin treatment was coherent with systemic responses. The good clinical response in most patients reflected symptom improvement.

Tumor shrinkage and improved quality of life in a heavily pretreated metastatic breast cancer patient treated with eribulin.

Eribulin mesylate is approved for the treatment of metastatic breast cancer after progression with anthracyclines and taxanes. Here we report the case of a woman with triple-negative breast cancer who, after nine lines of chemotherapy, showed striking primary tumor shrinkage and regression of metastatic lesions with eribulin treatment. This response allowed the patient to undergo debulking surgery. Even though the patient was heavily pretreated, eribulin was well tolerated and improved her quality of life. Biological analysis of tumor specimens was performed to investigate the underlying mechanism of action of the drug.

Lung infiltrates in cancer patients: differentiating metastases from bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a rare condition that affects oncological patients, often during or after chemotherapy, and can easily be mistaken for lung metastases. BOOP should be taken into consideration in cases when patchy nodular infiltrates with uncertain behavior appear in the lung; these infiltrates are often unresponsive to treatment with antibiotics. We report a case in which a patient treated for transitional cell bladder carcinoma with surgery and adjuvant chemotherapy developed multiple bilateral pulmonary nodules one month after the end of treatment.

Safe chemotherapy and hormone therapy for treating early breast cancer in a glucose 6-phosphate dehydrogenase-deficient patient: case report.

Breast cancer is the leading cause of neoplasia-related deaths among women, but no data are available in the literature on the safe use of oncological treatments in glucose 6-phosphate dehydrogenase (G6PD)-deficient patients. This case report describes, for the first time, the treatment of a G6PD-deficient woman diagnosed with breast cancer who underwent adjuvant treatment after quadrantectomy and axillary node dissection. After conservative surgery, many patients require adjuvant treatment with hormone therapy (HT) and/or chemotherapy. Anthracyclines are considered a cornerstone in this setting but, because of their oxidative properties, are contraindicated in G6PD-deficient patients. Despite the absence of data in the literature on their use in G6PD-deficient patients, we chose to use docetaxel and cyclophosphamide because these agents were not predicted to elicit oxidative stress. The patient completed six cycles of docetaxel and cyclophosphamide chemotherapy, and no adverse reactions were observed. Tamoxifen was excluded as a HT as a nonoxidative agent was required; therefore, an aromatase inhibitor was used as adjuvant therapy. Considering the high frequency of breast cancer and G6PD deficiency worldwide, there are little data available in the literature on the oxidative properties of oncological drugs. The oncological community must report cases in which patients with hereditary enzymatic deficiencies are treated successfully with anticancer agents. This would enable clinicians to have access to data that would be very useful in the choice of a safe treatment program.