ABSTRACT
Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1-56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2-19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8-6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4-12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk.
Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/epidemiology , Genetic Predisposition to Disease , Adult , Age Factors , Breast Neoplasms/genetics , Epidemiological Monitoring , Female , Follow-Up Studies , Germany/epidemiology , Heterozygote , Humans , Incidence , Medical History Taking , Middle Aged , Mutation , Prospective Studies , Risk Assessment , Risk FactorsABSTRACT
OBJECTIVE: To assess both regional (vulvar) and overall (generalized) pain sensitivity in women with vulvodynia to determine whether both are increased, suggestive of altered central pain processing. METHODS: Seventeen patients (aged 18-60 years) with vulvodynia and 23 age-matched control subjects were included in this cross-sectional study. Pressure pain thresholds in the vulvar area were evaluated in 23 defined locations using a newly developed vulvodolorimeter. Peripheral pressure pain sensitivity was assessed by applying 1) continuously ascending pressures to 3 bilateral locations (thumb, deltoid, and shin), and 2) discrete pressure stimuli to the thumb using both an ascending and random sequence of varying pressures. RESULTS: Pain thresholds at all vulvar locations were lower in the women with vulvodynia than in pain-free control subjects. Similarly, peripheral pain thresholds were lower at the thumb in women with vulvodynia when obtained by discrete ascending or random staircase paradigms, as well as at the thumb, deltoid, and shin when tested by dolorimeter (P <.05). Findings were similar in both those with generalized vulvar dysesthesia and those with localized vestibulodynia. The quantitative results obtained with the vulvodolorimeter and with the more subjective cotton-tipped swab testing routinely used in diagnosis were strongly correlated. CONCLUSION: Women with vulvodynia displayed significantly increased pressure pain sensitivity in both the vulvar region and in peripheral body regions, suggesting a "central" component to the mechanisms mediating this disorder. Both the novel vulvodolorimeter and the thumb pressure stimulator may assist in future experimental tests of this and related hypotheses.
