Homozygous boricua TBCK mutation causes neurodegeneration and aberrant autophagy

Brain damage can occasionally result in paradoxical functional benefit, which could help identify therapeutic targets for neuromodulation. However, these beneficial lesions are rare and lesions in multiple different brain locations can improve the same symptom. Using a technique called lesion network mapping, we show that heterogeneous lesion locations resulting in tremor relief are all connected to common nodes in the cerebellum and thalamus, the latter of which is a proven deep brain stimulation target for tremor. These results suggest that lesion network mapping can identify the common substrate underlying therapeutic lesions and effective therapeutic targets. Ann Neurol 2018;83:153–157     

Risk of metachronous breast cancer after BRCA mutation–associated ovarian cancer

BACKGROUND:

This study sought to estimate the risk of breast cancer (BC) after a diagnosis of ovarian cancer (OC) associated with mutation of the BRCA1/2 (breast cancer, early onset) genes (BRCA‐OC).

METHODS:

The Memorial Sloan‐Kettering Cancer Center and the University of Pennsylvania, clinical genetics databases were searched to identify women with BRCA‐OC who participated in genetic testing and follow‐up studies from 1995 to 2009. The primary objective was to determine the risk of developing BC after BRCA‐OC. Overall survival (OS) and BC‐free survival (BCFS) were determined by the Kaplan‐Meier method; patients were censored at the time of last follow‐up.

RESULTS:

A total of 164 patients had BRCA‐OC (115 with BRCA1; 49 with BRCA2). Of these 164 patients, 152 developed OC prior to BRCA testing (median time to testing, 2.4 years [0.01‐55 years]). Median follow‐up from OC for those not developing BC was 5.8 years (0.25‐55.6 years). There were 46 deaths, but none were due to BC. The 5‐ and 10‐year OS were 85% (95% confidence interval [CI] = 0.78, 0.90) and 68% (95% CI = 0.59, 0.76), respectively. There were 18 metachronous BC diagnoses. The 5‐ and 10‐year BCFS were 97% (95% CI = 0.92, 0.99) and 91% (95% CI = 0.82, 0.95), respectively. A subset of 64 women were tested either before or within 12 months of BRCA‐OC. In this pseudo‐incident subset, 5‐ and 10‐ year OS was 71% (95% CI = 0.53, 0.83) and 62% (95% CI = 0.44, 0.75), respectively, and 5‐ and 10‐year BCFS were 100% and 87% (95% CI = 0.56, 0.96), respectively.

CONCLUSIONS:

OS was dominated by OC deaths. Metachronous BC risk was lower than reported for unaffected BRCA mutation carriers. These results support nonsurgical management of BC risk in women with BRCA‐OC. Cancer 2013. © 2012 American Cancer Society.     

Psychiatric implications of cancer genetic testing

As genetic testing for hereditary cancer syndromes has transitioned from research to clinical settings, research regarding its accompanying psychosocial effects has grown. Men and women being tested for hereditary cancer syndromes may experience some psychological distress while going through the process of testing or after carrier status is identified. Psychological distress appears to decrease over the course of the first year and it is typically not clinically significant. Longer term studies show mixed results with some mutation carriers continuing to experience elevated distress. Baseline distress is the greatest risk factor for both immediate (weeks‐12 months) and long‐term psychological distress (18 mo‐8 years post genetic testing). In addition to baseline psychological distress, other risk factors can be identified to help identify individuals who may need psychosocial interventions during the genetic testing process. The challenges of providing clinical care to the growing population of individuals identified to be at increased risk for heritable cancers present opportunities for research and new models of care. Cancer 2015;121:341–360. © 2014 American Cancer Society.