Nuclear PARP-1 is overexpressed during the malignant transformation of the breast, particularly in triple-negative tumors, and independently predicts poor prognosis in operable invasive breast cancer.

A more aggressive molecular phenotype and high breast density were identified in breast tumors that truly arise in the interval between screenings.

Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

Purpose: Aromatase inhibitor (AI) associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. We wished to establish the optimal concentration of 25(OH)D that prevents or minimizes arthralgia. Methods:We used a prospective cohort of 290 women starting AI in whom baseline vitamin D was measured. All received daily vitamin D3 (800 IU) with calcium. Women with baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D3 orally every two weeks. The primary outcome was incident or worsening joint pain derived from baseline and three month VAS for joint pain. Regression models were used to analyse the association between vitamin D concentrations at 3 months and pain adjusting for age, BMI, season when the sample was drawn, aromatase inhibitor (exemestane vs letrozole/anastrozole), prior tamoxifen therapy, baseline NTX, and previous fracture.Results: 90% of women had a 25(OH)D <30 ng/ml at baseline. After supplementation (daily 800 IU and additional additional 16,000 IU every two week), 50% of them still failed to reach adequate concentrations at three months. In the whole cohort, there was an increase in joint pain (mean 1.16 points SD 2.66; p<0.001) and the increase was significantly (p= 0.02) attenuated in those that reached concentrations of 25(OH)D of ≥40 ng/ml, with a lower risk of incident arthralgia (OR 0.12 ** [0.03 to 0.40]).Conclusion: A target concentration of 40ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.