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Context Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival.Objective To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. Design and SettingRetrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PatientsThe study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison.Main Outcome Measures Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advancedstage (III and IV) cases. ResultsHereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1-vs BRCA2-linked patients (54 vs 62 years; P= .04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (PϽ.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P = .03). ConclusionsAlthough BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advancedstage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

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Objective To assess quadriceps strength and fatigability by using femoral nerve magnetic stimulation (FNMS) and their relationship to exercise capacity in patients with fibromyalgia syndrome (FMS) and healthy controls. Methods Twenty‐two women (11 with FMS, 11 controls) performed a maximal incremental cycling test and a quadriceps fatigue test on 2 separate visits. For quadriceps assessment, we used FNMS during and after maximum voluntary contraction (MVC) to evaluate central and peripheral factors of neuromuscular fatigue. Subjects performed sets of 10 intermittent (5 seconds on/5 seconds off) isometric contractions starting at 10% MVC, in 10% MVC increments from one set to another until exhaustion. Neuromuscular fatigue was assessed with FNMS after each set. Results FMS patients had reduced initial MVC compared to controls (mean ± SD 102 ± 18 versus 120 ± 24 Nm; P < 0.05) without significant impairment of voluntary activation (mean ± SD 93.5% ± 3.0% versus 93.1% ± 3.4%; P = 0.74). During the fatigue task, FMS patients exhibited a greater fall in evoked muscular responses (mean ± SD −26% ± 6% versus −16% ± 8% at set 50% MVC; P < 0.05), but not in MVC (mean ± SD −24% ± 7% versus −19% ± 4% at set 50% MVC; P = 0.12). During the cycling test, FMS patients had lowered maximal exercise capacity and an enhanced rate of perceived exertion (RPE) compared to controls. The percent reduction in evoked muscular responses during the quadriceps fatigue test correlated with maximum oxygen consumption (r = 0.56, P < 0.05) and RPE at submaximal intensity (r = 0.84, P < 0.05) during cycling. Conclusion Greater impairment in muscle contractility is associated with enhanced perception of exertion and reduced maximal exercise capacity in FMS patients. Neuromuscular impairments should be considered as an important factor underlying functional limitations in FMS patients.