Article

Survival in hereditary breast cancer associated with germline mutations of BRCA2.

Family Cancer Clinic and Department of Medical Registration, Daniel den Hoed Cancer Center, University Hospital Rotterdam, The Netherlands.
Journal of Clinical Oncology (impact factor: 18.37). 12/1999; 17(11):3396-402. pp.3396-402
Source: PubMed

ABSTRACT Breast cancer in BRCA1 and BRCA2 gene-mutation carriers may differ from so-called sporadic breast cancer in clinical features and behavior. These potential differences may be of importance for the prevention, screening, and, ultimately, treatment of breast cancer in women with such germline mutations. Thus far, there have been very few studies on the survival of BRCA2-associated breast cancer patients.
We determined the disease-free and overall survival of 28 breast cancer patients from 14 consecutive families with eight different BRCA2 germline mutations. These patients' survival and tumor characteristics were compared with those of a control group of 112 sporadic breast cancer patients matched to them by age and year of diagnosis.
The 5-year disease-free survival was 52% for each group (P =.91); the overall survival was 74% for BRCA2 carriers and 75% for sporadic cases (P =.50). At the time of diagnosis, tumors from the BRCA2 carriers were borderline significantly larger in comparison to the tumors in sporadic cases (P =.05), but axillary nodal status was not significantly different in the two groups (node-negativity, 63% v 52. 8%, respectively; P =.34). With respect to steroid receptor status, BRCA2-associated tumors were more likely to be steroid receptor-positive, especially regarding progesterone receptor status (100% v 76.7% positive, respectively; P =.06). Stage-adjusted recurrence and death rates were nonsignificantly better for BRCA2 cases (hazard ratios of 0.84 and 0.59 [P =.61 and P =.19], respectively). In contrast, after 5 years, the rate of metachronous contralateral breast cancer in BRCA2 patients was 12% (v 2% in controls; P =.02).
Patients with hereditary breast cancer due to BRCA2 have a similar prognosis when compared with age-matched sporadic breast cancer patients. Contrary to our previous observation regarding BRCA1-associated breast cancer, BRCA2 tumors tended to be steroid receptor-positive, instead of steroid receptor-negative.

0 0
 · 
0 Bookmarks
 · 
25 Views
  • Source
    Article: The promise of microarrays in the management and treatment of breast cancer.
    [show abstract] [hide abstract]
    ABSTRACT: Breast cancer is the most common malignancy afflicting women from Western cultures. Developments in breast cancer molecular and cellular biology research have brought us closer to understanding the genetic basis of this disease. Recent advances in microarray technology hold the promise of further increasing our understanding of the complexity and heterogeneity of this disease, and providing new avenues for the prognostication and prediction of breast cancer outcomes. These new technologies have some limitations and have yet to be incorporated into clinical use, for both the diagnosis and treatment of women with breast cancer. The most recent application of microarray genomic technologies to studying breast cancer is the focus of this review.
    Breast cancer research: BCR 02/2005; 7(3):100-4. · 5.24 Impact Factor
  • Source
    Article: Are BRCA1- and BRCA2-related breast cancers associated with increased mortality?
    [show abstract] [hide abstract]
    ABSTRACT: There has been contradictory evidence as to whether BRCA1 associated breast cancers have a poorer prognosis than non-BRCA1 cancers. In this issue of Breast Cancer Research Robson and colleagues provide further evidence for poorer survival in BRCA1 carriers and show that it could be attributed to failure to treat small node-negative grade 3 breast cancers with chemotherapy. There still remains little evidence for a survival difference for BRCA2 related breast cancers. Although the high contralateral breast cancer risk is confirmed by this study there is no real evidence for an increase in ipsilateral recurrence or new primary breast cancers in mutation carriers up to the 10-year point.
    Breast cancer research: BCR 02/2004; 6(1):E7. · 5.24 Impact Factor
  • Source
    Article: A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment.
    [show abstract] [hide abstract]
    ABSTRACT: The prognostic significance of germline mutations in BRCA1 and BRCA2 in women with breast cancer remains unclear. A combined analysis was performed to address this uncertainty. Two retrospective cohorts of Ashkenazi Jewish women undergoing breast-conserving treatment for invasive cancer between 1980 and 1995 (n = 584) were established. Archived tissue blocks were used as the source of DNA for Ashkenazi Jewish BRCA1/BRCA2 founder mutation analysis. Paraffin-embedded tissue and follow-up information was available for 505 women. Genotyping was successful in 496 women, of whom 56 (11.3%) were found to carry a BRCA1/BRCA2 founder mutation. After a median follow-up period of 116 months, breast cancer specific survival was worse in women with BRCA1 mutations than in those without (62% at 10 years versus 86%; P < 0.0001), but not in women with the BRCA2 mutation (84% versus 86% at 10 years; P = 0.76). Germline BRCA1 mutations were an independent predictor of breast cancer mortality in multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.2-4.8; P = 0.01). BRCA1 status predicted breast cancer mortality only among women who did not receive chemotherapy (hazard ratio 4.8, 95% confidence interval 2.0-11.7; P = 0.001). The risk for metachronous ipsilateral cancer was not greater in women with germline BRCA1/BRCA2 founder mutations than in those without mutations (P = 0.68). BRCA1 mutations, but not BRCA2 mutations, are associated with reduced survival in Ashkenazi women undergoing breast-conserving treatment for invasive breast cancer, but the poor prognosis associated with germline BRCA1 mutations is mitigated by adjuvant chemotherapy. The risk for metachronous ipsilateral disease does not appear to be increased for either BRCA1 or BRCA2 mutation carriers, at least up to 10 years of follow up.
    Breast cancer research: BCR 01/2004; 6(1):R8-R17. · 5.24 Impact Factor

Keywords

112 sporadic breast cancer patients
 
14 consecutive families
 
28 breast cancer patients
 
5-year disease-free survival
 
age-matched sporadic breast cancer patients
 
axillary nodal status
 
BRCA2 cases
 
BRCA2 patients
 
BRCA2 tumors
 
BRCA2-associated breast cancer patients
 
BRCA2-associated tumors
 
clinical features
 
control group
 
different BRCA2 germline mutations
 
germline mutations
 
metachronous contralateral breast cancer
 
patients' survival
 
progesterone receptor status
 
sporadic cases
 
steroid receptor status