Purpose:To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. Experimental Design: Histopathologic material from182 tumors in BRCA1mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin. Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls. Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.

BackgroundAdjuvant radiotherapy (RT) of regional lymph nodes (LN) in early breast cancer is still a matter of debate. RT increases the Overall survival (OS) rate of breast cancer patients after breast conserving surgery and after mastectomy in patients with involved LN. The contribution of RT to regional LN to this improvement was poorly identified. Recently, the results of three large randomized trials addressing this question were published as full papers.Material and methodsPublished data of the MA.20 (n = 1832), the EORTC22922–10925 (EORTC) (n = 4004) trial and the French trial (n = 1334) were the foundation of this meta-analysis. Major eligibility criteria were positive i) axillary LN (all trials), ii) LN negative disease with high risk for recurrence (MA.20), and iii) medial/central tumor location (French, EORTC). The MA.20 and the EORTC trial analyzed the effect of additional regional RT to the internal mammary (IM) LN and medial supraclavicular (MS) LN, whereas in the French trial all patients received RT to the MS-LN and solely RT to the IM-LN was randomized. Primary endpoint was OS. Secondary endpoints were disease-free survival (DFS) and distant metastasis free survival (DMFS).ResultsRegional RT of MS-LN and IM-LN (MA.20 and EORTC) resulted in a significant improvement of OS [Hazard Ratio (HR) 0.88 (95 % CL 0.78 - 0.99)]. Adding results of the French trial and using a random effects model to respect the different design of the French trial, the effect on OS of regional RT remained significant [HR 0.90 (95 % CL 0.82 - 0.99)]. The absolute benefits in OS were 1 % in the MA.20 trial at 10 years, 1.6 % in the EORTC trial at 10 years, and 3.3 % in the French trial at 10 years (not significant in single trials). Regional RT of MS-LN and IM-LN (MA.20 and EORTC) yielded to a significant improvement of DFS [HR 0.86 (95 % CL 0.78 - 0.95)] and DMFS [HR 0.84 (95 % CL 0.75 - 0.94)].ConclusionAdditional regional RT to the internal mammary and medial supraclavicular LN statistically significantly improved DFS, DMFS, and OS in stage I-III breast cancer.

Purpose/Objective(s)It is currently unclear whether patients with low risk breast cancer receiving adjuvant endocrine therapy need adjuvant radiation therapy after breast conserving surgery. The data of randomized trials are available.Materials/MethodsIn a database search 5 randomized trials including in total 3766 mostly elderly patients with early stage breast cancer treated either with adjuvant endocrine therapy or with endocrine therapy and additional whole breast radiation after breast conserving surgery were identified. Published hazard ratios for time to local recurrence were the basis of our meta-analysis. Meta-analysis of the effect sizes on local recurrence was performed using a random effects model based on parameter estimates of log hazard ratios in Cox models and their standard errors. Furthermore, overall survival was examined.ResultsAdjuvant hormone therapy alone in mostly older patients with low risk breast cancer resulted in significantly shorter time to local relapse compared to radiation therapy combined with hormone therapy (Hazard Ratio: 6.8, 95% CI: 4.23–10.93, p < 0.0001) . There was no significant difference for overall survival.ConclusionAdditional radiation therapy to hormone therapy did improve local relapse in breast cancer patients but did not show significant impact on overall survival.

Purpose: Breast cancer (BC) is the most frequent female carcinoma and the major cause of death in women aged 35–50 years. The total number of patients surviving BC and especially the morbidity rate of patients below the age of 55 years has increased significantly in the last several years. As a consequence, the number of BC patients suffering from the long-term effects of estrogen deficiency due to adjuvant treatment is increasing. At present, hormone replacement therapy (HRT) following BC treatment is applied individually and mainly depends on the severity of postmenopausal symptoms (PMS) experienced by these patients. Patients and Methods: In a retrospective study (total n = 185 BC patients, 64 with and 121 without HRT), the effect of HRT during or after adjuvant therapy [chemotherapy and/ or (anti-) hormonotherapy] has been investigated. The surveillance period was up to 60 months. Evaluated were HRT effects on (1) PMS measured by a comprehensive life quality questionnaire, (2) bone mineral density (BMD) measured by osteodensitometry and (3) morbidity as well as mortality rates. Results: Both groups did not differ with regard to tumor stage, lymph node involvement, metastasis, grading, and steroid hormone receptor status. A reduction in PMS was significant in women taking HRT (p < 0.001), especially in the subgroup of women ≤50 years (p < 0.0001). For both age groups, the median reduction in BMD (z-score) was less in women receiving HRT (≤50 years: without HRT –1.99 vs. with HRT –0.95, p < 0.05; >50 years: without HRT –2.29 vs. with HRT –1.19, p < 0.01). There were no statistically significant differences regarding morbidity and mortality (p = 0.29). Conclusion: In this study of BC patients, the use of HRT shows positive effects on PMS and BMD. There was no significant influence on morbidity or mortality. However, a reevaluation of HRT in the routine management of BC patients should await the results of prospective randomized trials.

We conclude that risk reducing surgery is highly effective.