ABSTRACT
OBJECTIVES: To review non-surgical prevention strategies in women with hereditary breast and ovarian cancer syndromes. CONTENT: Women with a gBRCA1 or 2 mutations face a high cumulative breast and ovarian cancer risk. While bilateral mastectomy (PBM) and bilateral salpingo-oophrectomy (PBSO) profoundly reduce the respective cancer risks, they are also associated with considerable side effects. There is therefore an urgent need for alternative and non-surgical risk reduction options. Tamoxifen and aromatase inhibitors have both been evaluated in secondary prevention, but their benefit in primary prevention is currently unknown in BRCA mutation carriers. In addition, their use is compromised by their side effect profile which makes them less appealing for a use in chemoprevention. SUMMARY AND OUTLOOK: Denosumab is a well-tolerated osteoprotective drug, which has been demonstrated to have a potential preventive effect particularly in BRCA1-deficient models in vitro. The prospectively randomized double-blind BRCA-P trial is currently investigating the preventative effect of denosumab in healthy BRCA1 germ line mutation carriers.
Subject(s)
Adiponectin/blood , Biomarkers/blood , Hereditary Breast and Ovarian Cancer Syndrome/blood , Hereditary Breast and Ovarian Cancer Syndrome/epidemiology , Aged , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Biomarkers, Tumor , Cross-Sectional Studies , Disease Susceptibility , Genetic Predisposition to Disease , Hereditary Breast and Ovarian Cancer Syndrome/etiology , Hereditary Breast and Ovarian Cancer Syndrome/therapy , Humans , Lipids/blood , Middle Aged , MutationABSTRACT
BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers. Premenopausal RRSO is hypothesized to increase fracture risk more than natural menopause. Elevated bone turnover markers (BTMs) might predict fracture risk. We investigated BTM levels after RRSO and aimed to identify clinical characteristics associated with elevated BTMs. METHODS: Osteocalcin (OC), procollagen type I N-terminal peptide (PINP) and serum C-telopeptide of type I collagen (sCTx) were measured in 210 women ≥ 2 years after RRSO before age 53. BTM Z-scores were calculated using an existing reference cohort of age-matched women. Clinical characteristics were assessed by questionnaire. RESULTS: BTMs after RRSO were higher than age-matched reference values: median Z-scores OC 0.11, p = 0.003; PINP 0.84, p < 0.001; sCTx 0.53, p < 0.001 (compared to Z = 0). After excluding women with recent fractures or BTM interfering medication, Z-scores increased to 0.34, 1.14 and 0.88, respectively. Z-scores for OC and PINP were inversely correlated to age at RRSO. No correlation was found with fracture incidence or history of breast cancer. CONCLUSIONS: Five years after RRSO, BTMs were higher than age-matched reference values. Since elevated BTMs might predict higher fracture risk, prospective studies are required to evaluate the clinical implications of this finding.
Subject(s)
Bone and Bones/metabolism , Hereditary Breast and Ovarian Cancer Syndrome/etiology , Hereditary Breast and Ovarian Cancer Syndrome/metabolism , Ovariectomy , Salpingectomy , Adult , Aged , Biomarkers , Bone Resorption/metabolism , Collagen Type I/metabolism , Female , Hereditary Breast and Ovarian Cancer Syndrome/epidemiology , Humans , Middle Aged , Osteocalcin/metabolism , Peptide Fragments/metabolism , Peptides/metabolism , Procollagen/metabolism , Risk Factors , Risk Reduction BehaviorABSTRACT
Objetivo: El presente estudio pretende que el ginecólogo clínico tome conciencia de la existencia de tumores ginecológicos de aparición sincrónica en una misma paciente durante el proceso diagnóstico de una neoplasia ginecológica, sobre todo en casos de antecedentes de cáncer de tipo familiar. Se describen varios síndromes consistentes en la aparición de tumores de tipo familiar que facilitan la presencia de tumores ginecológicos sincrónicos. Sujetos y métodos: Se analiza la casuística del Hospital de Manacor desde 1997 hasta 2006. Resultados: Los casos de tumores ginecológicos sincrónicos suponen el 0,83% de los tumores intervenidos en el período estudiado. Conclusiones: Aunque infrecuentes, estos tumores ginecológicos sincrónicos deben de tenerse en cuenta para que no pasen inadvertidos, sobre todo en pacientes con historia de cáncer familiar o portadoras de algunos síndromes genéticos. Una exploración dirigida a eliminar la presencia de otra neoplasia, aparte de la que estamos diagnosticando, es conveniente (AU)
Objective: To alert clinicians to the possibility of synchronous tumors in patients with gynecological cancer. An important tool in diagnosis is the family history. We describe several familial syndromes involving the development of synchronous gynecological tumors. Subjects and methods: We studied all cases of synchronous gynecological tumors in the Manacor Hospital from 1997 to 2006. Results: Synchronous gynecologic tumors represented 0.83% of all gynecological neoplasms treated in our center in the period studied. Conclusions: This kind of tumor is uncommon but should be considered by clinicians, especially in women with a familial history of cancer or in those with certain genetic syndromes. Examination aimed at excluding the presence of synchronous tumors is recommended (AU)
