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Tumour diploidy and survival in breast cancer patients with BRCA2 mutations
Ist Teil von
Breast cancer research and treatment, 2013-07, Vol.140 (2), p.375-384
Ort / Verlag
Boston: Springer US
Erscheinungsjahr
2013
Quelle
SpringerLink Journals
Beschreibungen/Notizen
It is not well known to what extent carrying a
BRCA2
mutation affects the survival of women with breast cancer and prognostic factors among
BRCA2
-positive women warrant investigation. Using a record linkage approach we compared the long-term survival in carriers and noncarriers of an inherited
BRCA2
founder mutation (999del5), and sought to identify prognostic factors among the
BRCA2
mutation-positive subset, including markers of genetic instability (aneuploidy) and mitotic activity (S-phase fraction). We established the genetic status of 2,967 Icelandic breast cancer patients (215 mutation carriers and 2,752 noncarriers) diagnosed from 1955 to 2004, representing 72 % of all cases diagnosed in the country during this period. Tumour ploidy and S-phase fraction were assessed on tumour cells by DNA flow cytometry. Prognostic factors were assessed blindly with respect to mutation status. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival by
BRCA2
status, using Cox regression. After a median follow-up of 9.5 years,
BRCA2
mutation carriers had a higher risk of death from breast cancer than noncarriers (HR 1.64, 95 % CI 1.24–2.16,
p
< 0.001). The risk increase was restricted to women with diploid tumours (HR 3.03, 95 % CI 1.91–4.79,
p
< 0.001). Among breast cancer patients with aneuploid tumours, survival of carriers was similar to that of noncarriers (HR 0.76, 95 % CI 0.41–1.41,
p
= 0.38). Increased tumour size and a positive nodal status predicted worse prognosis in all patients, whereas the highly correlated prognostic factors diploidy, low proliferative activity and a positive estrogen receptor status had reverse effects in mutation carriers and noncarriers. Breast cancer patients who carry the Icelandic founder
BRCA2
mutation have inferior long-term survival than noncarriers, but the adverse prognosis is restricted to mutation carriers with diploid, slowly proliferating tumours.