Risk of Prostate Cancer Associated With Familial and Hereditary Cancer Syndromes.

PURPOSE: Recently developed clinical guidelines suggest that men in families with specific cancer syndromes, such as hereditary breast and ovarian cancer (HBOC), consider genetic testing, especially in the setting of aggressive disease. However, although a family history (FH) of the same disease among close relatives is an established risk factor for prostate cancer (PC), a direct comparison of PC risk for men with each syndrome in a single population is needed. METHODS: The Utah Population Database was used to identify 619,630 men, age ≥ 40 years, who were members of a pedigree that included at least 3 consecutive generations. Each man was evaluated for FH of hereditary PC (HPC), HBOC, and Lynch syndrome (LS) and for his own PC status. PC occurrences (N = 36,360) were classified into one or more subtypes: early onset (EO), lethal, and/or clinically significant. Relative risks (RRs) associated with each subtype, adjusted for important covariables, were calculated in STATA using a modified Poisson regression with robust error variances to obtain corresponding RR CIs for each FH definition. RESULTS: An FH of HPC conveyed the greatest relative risk for all PC subtypes combined (RR, 2.30; 95% CI, 2.22 to 2.40), followed by HBOC and LS (both with 1 < RR < 2 and statistically significant). The strongest risks associated with FH were observed for EO disease in all pedigree types, consistent with the contribution of genetic factors to disease occurrence. CONCLUSION: In this large, population-based, family database, the risk of PC varied by cancer FH and was most strongly associated with EO disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance.

Prognosis of BRCA1/2-negative breast cancer patients with HBOC risk factors compared with sporadic breast cancer patients without HBOC risk factors.

OBJECTIVE: Demands for genetic counseling with BRCA1/2 examination have markedly increased. Accordingly, the incidence of uninformative results on BRCA1/2 mutation status has also increased. Because most patients examined for BRCA1/2 mutation have a high risk of hereditary breast and/or ovarian cancer, many patients suffer psychological distress even when the BRCA1/2 result is negative. We compared oncological outcomes between BRCA1/2-negative breast cancer with high risk of hereditary breast and/or ovarian cancer and sporadic breast cancer without risk of hereditary breast and/or ovarian cancer. METHODS: The criteria for high risk for hereditary breast and/or ovarian cancer were defined as family history of breast and/or ovarian cancer in first- or second-degree relative, early onset breast cancer at <35 years old and bilateral breast cancer. Patients were matched maximally 1:3 into those who identified as negative for BRCA1/2 mutation with risk of hereditary breast and/or ovarian cancer (study group) and those who were not examined for BRCA1/2 mutation without risk for hereditary breast and/or ovarian cancer (control group). Matched variables were pathologic stage, estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status. RESULTS: All matching variables were successfully matched. Median follow-up duration was 57.8 months. There was no significant difference between the groups in disease-free survival (log-rank P = 0.197); however, the study group showed significantly better overall survival and breast cancer-specific survival (both P < 0.0001). We conducted subgroup analysis in the middle-aged group (36-54) and showed no significant difference for disease-free survival (P = 0.072) but significantly better overall survival and breast cancer-specific survival in the study group (P = 0.002 and P < 0.0001). CONCLUSIONS: BRCA1/2-negative breast cancer patients who had hereditary breast and/or ovarian cancer risk factors showed similar disease-free survival and better overall survival and breast cancer-specific survival compared with those with sporadic breast cancer without hereditary breast and/or ovarian cancer risk factors.

[Cost-effectiveness of risk-reducing salpingo-oophorectomy in cases of BRCA1 gene mutation in Colombia]. / Costo efectividad de la cirugía reductora de riesgo en trompas y ovarios en casos con mutación del gen BRCAI en Colombia.

OBJECTIVE: To assess the usefulness of risk reduction salpingo-oophorectomy in cases with mutation of the BRCA1 gene in Colombia. MATERIAL AND METHODS: Cost-effectiveness analysis in which three processes are incorporated: a. Patients with screening tests for breast and ovarian cancer. b. Risk reduction surgery in the fallopian tubes and ovaries c. Reductive surgery in the fallopian tubes and ovaries with bilateral mastectomy. The outcome is evaluated as the gain in years of survival. RESULTS: The cohort with risk reduction surgery in the fallopian tubes and ovaries and bilateral mastectomy is the one with the highest gain with 13 years, while the risk reduction surgery in the fallopian tubes and ovaries gain 4.95 years with respect to the follow-up group. CONCLUSIONS: The three options evaluated are acceptable, but of them the one with the greatest gain in survival is the combination of risk-reducing surgery in the fallopian tubes and ovaries with bilateral mastectomy.

OBJETIVO: Evaluar la utilidad de la cirugía reductora de riesgo en trompas y ovarios en casos con mutación del gen BRCA1 en Colombia. MATERIAL Y MÉTODOS: Análisis de costo-efectividad en el que se incorporan tres procesos: a. Pacientes con pruebas de tamización para cáncer de mama y ovario. b. cirugía reductora de riesgo en trompas y ovarios c. cirugía reductora de riesgo en trompas y ovarios con mastectomía bilateral. Se evalúa como desenlace la ganancia en años de supervivencia. RESULTADOS: La cohorte con cirugía reductora de riesgo en trompas y ovarios y mastectomía bilateral es la de mayor ganancia con 13 años mientras que la cirugía reductora de riesgo en trompas y ovarios gana 4,95 años con respecto al grupo de seguimiento. CONCLUSIONES: Las tres opciones evaluadas son aceptables, pero de ellas la de mayor ganancia en la supervivencia es la combinación de cirugía reductora de riesgo en trompas y ovarios con mastectomía bilateral.

Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?

The aim of the current analysis is to evaluate any differences of breast or ovarian cancer age at diagnosis between mothers and daughters carrying the c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who reported a first breast or ovarian cancer in their mother carrying the c.3481_3491del11 mutation, was identified in 37 different families including members with breast and/or ovarian cancer at the Oncology Institute of Lorraine. Twelve mothers underwent genetic testing. Twenty-five pairs of the 38 mothers-daughters pairs with c.3481_3491del11 mutation were affected by breast cancer and 13 pairs by ovarian cancer. Clinical and genetic data were collected from medical files and family pedigrees. Analyses were conducted for each cancer type. We investigated an early breast cancer detection effect due to early screening programs and also an increased breast tumor aggression. Since major improvements in breast cancer clinical management and imaging techniques appeared after 1980, we compared the age at breast cancer diagnosis and the age at death in mothers and daughters before and after 1980, first, in the group of women including mothers and daughters taken together and then in mothers and daughters separately. The mean age at breast cancer diagnosis was 45.28 ± 10.27 years in mothers and 39.80 ± 7.79 years in daughters (p = 0.026). The difference of age at ovarian cancer diagnosis in mother-daughter pairs was 8.62 ± 12.76 years (p = 0.032). When considering the group of women including mothers and daughters taken together, no significant difference of age at breast cancer diagnosis was found between women affected before 1980 and those affected after 1980 (p = 0.577). However, the age at death increased in these women after 1980 (p = 0.026). Comparison of age at breast cancer diagnosis in mothers and daughters separately, showed that daughters were affected at an earlier age after 1980 (p = 0.002). Daughters had a poor prognosis and died earlier than mothers after 1980. Our results may have reflected genetic anticipation in c.3481_3491del11 mutation breast and ovarian cancer families. In order to confirm our findings, a larger cohort would provide more precision to the difference of ages at breast or ovarian cancer diagnosis between mothers and daughters and more powerful statistical analyses. Increased aggression in daughters' tumors compared to those of mothers could be also considered as a parameter of genetic anticipation. Complete information on tumor profile and proliferation would allow us to study genetic anticipation by comparing the tumor phenotypes between mothers and daughters in the future.