Overall, 5-10% of primary breast cancer (BC) are inherited and about 15-20% are familial. BRCA1/2 genes sustain the hereditary breast/ovarian cancer (HBOC) syndrome. The family features that suggest hereditary BC predisposition include: multiple cases of BC and ovarian cancer (OC) in different generations, an early onset age at diagnosis of BC, multiple primary cancers in the same individual and male BC. In BRCA1 mutation carriers, mean cumulative risk at age 70 years is 57% for BC and 40% for OC. Moreover, in BRCA2 mutation carriers mean cumulative risk at age 70 years is 49% for BC and 18% for OC. Several studies reported contradictory data concerning risk of cancer at sites different than BC and OC in BRCA1 and BRCA2 mutation carriers. Hereditary and familial BC needs a specific management trough oncogenetic counselling from risk identification to risk management. In Italy a model of oncogenetic counseling was designed and promoted at the “Screening and Follow-up for Hereditary and Familial Cancer” Unit at “Federico II” University in Naples. The model was validated by five clinically oriented centers within national research projects supported by the Ministry of Research since 1999 to 2005. This model is conducted in different steps to promote awareness in subjects at hereditary or familial risk. The model is designed to entail a global approach to the patient affected by cancer and to disease-free at-risk subjects by a multidisciplinary team. Here, we reported the experience in Naples about the spectrum of related tumors in hereditary/familial BC in a series of 104 families referred for oncogenetic counseling. Based on family history of BC and/or OC, families were classified according to Modena model in hereditary with clustering (41 families; 39%), hereditary without clustering (27 families; 26%) and familial (36 families; 35%) groups. We registered other tumors different than BC in 275 cases, of which 117 cases in the hereditary with clustering group, 49 cases in the hereditary without clustering group and 109 cases in the familial group. We detected a higher percentage distribution of OC, prostate cancer and stomach cancer in the hereditary with clustering group than the other two groups. Uterine cancer was associated with the two groups specifically characterized by clustering BC, such as hereditary with clustering and familial groups. BRCA1/BRCA2 genotyping was performed in 44 subjects belonging to different families. Forty-three subjects were tested for BRCA1 gene with the detection of 10 distinct mutations. Thirty subjects were tested for BRCA2 gene with the detection of 6 distinct mutations. We also determined the percentage distribution of tumors in families with mutations of BRCA1/2 genes. Kidney/bladder cancer and stomach cancer were only detected in the families at BRCA1 genotype, while prostate cancer was only detected in the families at BRCA2 genotype. OC, uterus cancer and colon-rectum cancer clustered in both the families at BRCA1/BRCA2 genotype. Our experience suggests to be careful as possible in considering a specific clinical surveillance on the basis of risk categories and mutation status, until data derived from population-based studies will be available.

The cancer spectrum related to hereditary and familial breast and ovarian cancers

PENSABENE, MATILDE;CAPUANO, IDA;SPAGNOLETTI, ILARIA;DE MAIO, ELEONORA;PEPE, STEFANO;CONTEGIACOMO, ALMA
2009

Abstract

Overall, 5-10% of primary breast cancer (BC) are inherited and about 15-20% are familial. BRCA1/2 genes sustain the hereditary breast/ovarian cancer (HBOC) syndrome. The family features that suggest hereditary BC predisposition include: multiple cases of BC and ovarian cancer (OC) in different generations, an early onset age at diagnosis of BC, multiple primary cancers in the same individual and male BC. In BRCA1 mutation carriers, mean cumulative risk at age 70 years is 57% for BC and 40% for OC. Moreover, in BRCA2 mutation carriers mean cumulative risk at age 70 years is 49% for BC and 18% for OC. Several studies reported contradictory data concerning risk of cancer at sites different than BC and OC in BRCA1 and BRCA2 mutation carriers. Hereditary and familial BC needs a specific management trough oncogenetic counselling from risk identification to risk management. In Italy a model of oncogenetic counseling was designed and promoted at the “Screening and Follow-up for Hereditary and Familial Cancer” Unit at “Federico II” University in Naples. The model was validated by five clinically oriented centers within national research projects supported by the Ministry of Research since 1999 to 2005. This model is conducted in different steps to promote awareness in subjects at hereditary or familial risk. The model is designed to entail a global approach to the patient affected by cancer and to disease-free at-risk subjects by a multidisciplinary team. Here, we reported the experience in Naples about the spectrum of related tumors in hereditary/familial BC in a series of 104 families referred for oncogenetic counseling. Based on family history of BC and/or OC, families were classified according to Modena model in hereditary with clustering (41 families; 39%), hereditary without clustering (27 families; 26%) and familial (36 families; 35%) groups. We registered other tumors different than BC in 275 cases, of which 117 cases in the hereditary with clustering group, 49 cases in the hereditary without clustering group and 109 cases in the familial group. We detected a higher percentage distribution of OC, prostate cancer and stomach cancer in the hereditary with clustering group than the other two groups. Uterine cancer was associated with the two groups specifically characterized by clustering BC, such as hereditary with clustering and familial groups. BRCA1/BRCA2 genotyping was performed in 44 subjects belonging to different families. Forty-three subjects were tested for BRCA1 gene with the detection of 10 distinct mutations. Thirty subjects were tested for BRCA2 gene with the detection of 6 distinct mutations. We also determined the percentage distribution of tumors in families with mutations of BRCA1/2 genes. Kidney/bladder cancer and stomach cancer were only detected in the families at BRCA1 genotype, while prostate cancer was only detected in the families at BRCA2 genotype. OC, uterus cancer and colon-rectum cancer clustered in both the families at BRCA1/BRCA2 genotype. Our experience suggests to be careful as possible in considering a specific clinical surveillance on the basis of risk categories and mutation status, until data derived from population-based studies will be available.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/340260
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