Myelotoxicity induced by chemotherapy may become life-threatening. Neutropenia may be prevented by granulocyte colony-stimulating factors (GCSF), and epoetin may prevent anemia, but both cause substantial side effects and increased costs. According to non-established data, wheat grass juice (WGJ) may prevent myelotoxicity when applied with chemotherapy. In this prospective matched control study, 60 patients with breast carcinoma on chemotherapy were enrolled and assigned to an intervention or control arm. Those in the intervention arm (A) were given 60 cc of WGJ orally daily during the first three cycles of chemotherapy, while those in the control arm (B) received only regular supportive therapy. Premature termination of treatment, dose reduction, and starting GCSF or epoetin were considered as "censoring events." Response rate to chemotherapy was calculated in patients with evaluable disease. Analysis of the results showed that five censoring events occurred in Arm A and 15 in Arm B (P = 0.01). Of the 15 events in Arm B, 11 were related to hematological events. No reduction in response rate was observed in patients who could be assessed for response. Side effects related to WGJ were minimal, including worsening of nausea in six patients, causing cessation of WGJ intake. In conclusion, it was found that WGJ taken during FAC chemotherapy may reduce myelotoxicity, dose reductions, and need for GCSF support, without diminishing efficacy of chemotherapy. These preliminary results need confirmation in a phase III study.
Bilateral breast cancer is traditionally considered an indirect indicator of inherited predisposition to cancer. To appreciate the contribution of genetic determinants to bilateral breast cancer in Jewish women we genotyped 55 such women for the three predominant mutations in BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) that account for the overwhelming majority of BRCA mutations in high-risk Jewish families. Among women with bilateral breast cancer, 17 mutation carriers (17/55; 29.6%) were identified. Individual mutation frequencies were 18.5% (10/55) for 185delAG, 3.7% (2/55) for 5382insC and 7.4% (5/55) for 6174delT. Carrier rate was significantly higher (P < 0.0016) in women with bilateral breast cancer whose first tumour was diagnosed at or before 42 years of age (82%; 14/17) than in women diagnosed after 42 years of age (7.9%; 3/38). Among patients with bilateral breast cancer and positive family history 45% (14/31) carried a BRCA mutation. Of these 86% (12/14) had one breast cancer diagnosed at or before 42 years of age. Our results suggest that bilateral breast cancer per se, in most cases, does not reflect genetic predisposition, unless associated with early age of onset (first tumour diagnosed at or before 42 years of age). Although the relationship between young age and carrier state in women with bilateral breast cancer is strong, no significant association between family history and carrier state was found. We can thus speculate that women with early onset breast cancer who carry a BRCA1 or BRCA2 mutation are prone to acquire a second breast tumour.
This study uncovers disease characteristics by long-term follow-up in Ashkenazi early onset breast cancer (EOBC) patients, carriers of founder BRCA1/2 mutations compared to non-carriers of such mutations. An archives-retrospective design was conducted to study the pathological and clinical characteristics of 149 Ashkenazi Jewish EOBC patients (<42 years) who were referred consecutively to the oncogenetic clinic by the oncology centre at Rambam HealthCare Campus, as from 1995, with a mean follow-up of 13.61 years. Of 149 patients, 33 (22.1%) and 15 (10.1%) carried the founder BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT) mutations, respectively; and 101 (67.8%) were non-carriers of these mutations. Contralateral breast-cancer was predominant among BRCA1/2 carriers compared to non-carriers (14, 58.3%; 6, 60%; 7, 8.1%; respectively, p < .001). Ovarian cancer was diagnosed in two BRCA1 carriers and one non-carrier. Oestrogen and/or progesterone receptor negative tumours were majorly detected in BRCA1 carriers (n = 16, 57.1%) compared to BRCA2 carriers (n = 4, 30.8%) and non-carriers (n = 23, 25.3%) (p = .007). BRCA1 carriers and non-carriers developed contralateral breast cancer at an earlier age than BRCA2 carriers. BRCA2 carriers portrayed similar tumour characteristics to non-carriers. EOBC BRCA1/2 carriers are at risk to develop bilateral disease; however, they are similarly susceptible for local recurrence, distant metastases and mortality.
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