Role of BRCA2 mutation status on overall survival among breast cancer patients from Sardinia

Abstract

BackgroundGermline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA mutations on prognosis and survival of breast cancer patients is still debated. In this study, we investigated the role of such mutations on breast cancer-specific survival among patients from North Sardinia.MethodsAmong incident cases during the period 1997–2002, a total of 512 breast cancer patients gave their consent to undergo BRCA mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan-Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis.ResultsIn our series, patients carrying a germline mutation in coding regions and splice boundaries of BRCA1 and BRCA2 genes were 48/512 (9%). Effect on overall survival was evaluated taking into consideration BRCA2 carriers, who represented the vast majority (44/48; 92%) of mutation-positive patients. A lower breast cancer-specific overall survival rate was observed in BRCA2 mutation carriers after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets.ConclusionIn Sardinian breast cancer population, BRCA2 was the most affected gene and the effects of BRCA2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA2 mutation carriers and non-carriers.

Taxa de sobrevida na mulher com câncer de mama: estudo de revisão

“…28 Women with breast cancer who are Human Epidermal Growth Factor Receptor 2 (HER2) positive have a 30% to 50% risk of disease recurrence, using conventional therapies. The combined use of doxorubicin, cyclophosphamide, and paclitaxel, with one additional year of trastuzumab, demonstrates a 52% reduction in the recurrence of the disease and a 33% reduction in the mortality risk compared with women who did not receive trastuzumab.…”

“…The publications originated from 20 countries: Korea (six studies), [8][9][10][11][12][13] Japan (five studies), [14][15][16][17][18] Brazil (four studies), 3,[19][20][21] Canada (three studies), [22][23][24] United States (three studies), [25][26][27] Italy (three studies), [28][29][30] Switzerland (three studies), [31][32][33] France (two studies), 34,35 China (one study), 36 Singapore and Sweden (one study, study performed in both countries), 37 Scotland (one study), 38 Spain (one study), 39 Finland (one study), 40 India (one study), 41 England (two studies), 42,45 Mexico (one study), 43 Poland (one study), 44 and the Netherlands (one study). 46 From the aim established for this study, the variables to be investigated were defined: the study design, study site/country, number of subjects, age of the subjects, five year survival rate, disease-free five year survival rate, factors that contribute to the increase in survival rates.…”

BRCA1/2 and clinical outcome in a monoinstitutional cohort of women with hereditary breast cancer

“…Analogously, in Sardinia, whose population is genetically homogeneous, investigators did not find any significant difference in outcome between patients carrying BRCA2 mutations and those negative for BRCA2 mutations (most prevalent BRCA sequence variations), as well as no difference in survival among familial and sporadic BRCA2 mutatation cases (14).…”

Análise de custo-efetividade de programa para diagnóstico de mutação germinativa em genes BRCA1/2 e de estratégias preventivas para pacientes com câncer de ovário e seus familiares de primeiro grau

“….. Estudos prospectivos que apresentam risco relativo para câncer de mama após a realização de mastectomia bilateral profilática (45,(131)(132)(133) . (31,32,(136)(137)(138) . (141) .…”

“…Risco relativo para câncer de ovário após salpingoooforectomia redutora de risco Systematic Reviews and Meta-Analyses (PRISMA) (126) (31,32,(137)(138)(139) .…”