To the Editor: In the IMpassion130 trial, Schmid et al. (Nov. 29 issue)¹ found that combination therapy with atezolizumab plus nanoparticle albumin-bound (nab)–paclitaxel led to longer progression-free survival than placebo plus nab-paclitaxel among patients with metastatic triple-negative breast cancer. The effect was observed both in the intention-to-treat population and in the population of patients with tumors that were positive for programmed death ligand 1 (PD-L1). In this trial, the BRCA mutation profile of the patients was not reported in the published data. It has been widely reported that germline mutations in BRCA1 or BRCA2 cause DNA-repair defects and genomic instability.² . . .

In this study, we aimed to assess the cancer risk among patients with periodontal disease. Patients diagnosed with periodontal diseases at Hacettepe University between 2007 and 2012 were included and data on the diagnosis of any cancer after periodontal disease were collected from patient files. The age- and sex-standardized incidence rates (SIRs) were calculated using Turkish National Cancer Registry 2013 data. A total of 5199 patients were included. Median follow-up was 7.2 years. Patients with periodontal diseases had 17% increased risk of cancer compared with the expected counts for the corresponding age and sex groups (SIR: 1.17; 95% CI: 1.04–1.3, P = 0.006). The increased cancer risk was statistically significant in women (SIR: 1.24; 95% CI: 1.05–1.45, P = 0.008) but not in men. Among women with periodontal disease, the risks of breast cancer (SIR: 2.19) and head and neck cancer (SIR: 4.71) were significantly increased. Among men, the risks of prostate cancer (SIR: 1.84), head and neck cancer (SIR: 3.55), and hematological cancers (SIR: 1.76) were significantly increased. This study showed that periodontal diseases were associated with increased risk of several cancers. Besides other well-known benefits for health, the provision of oral/dental health should be considered and employed as a cancer prevention measure.

To the Editor: In the randomized, placebo-controlled Vitamin D and Type 2 Diabetes (D2d) trial involving persons at risk for type 2 diabetes, Pittas et al. (Aug. 8 issue)¹ found that vitamin D₃ supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. Investigators emphasized that the trial was planned not only for participants with vitamin D insufficiency, given ethical considerations. Although the mean baseline vitamin D levels are well balanced between the trial groups and above insufficiency limits, more than 20% of the participants in the placebo group . . .

Introduction: Impaired DNA damage response (DDR) and subsequent genomic instability is associated with carcinogenic process itself, but it also results in sensitivity of tumor cells to certain drugs and can be exploited to treat cancer by inducing deadly mutations or mitotic catastrophe. Exploiting DDR defects in breast cancer cells has been one of the main strategies in both conventional chemotherapy, targeted therapies or immunotherapies. Areas covered: In this review, the authors first discuss DDR mechanisms in healthy cells and DDR defects in breast cancer, then focus on current therapies and developments in the treatment of DDR deficient breast cancer. Expert opinion: Among conventional chemotherapeutics, platinum-based regimens in particular seem to be effective in DDR-deficient patients. PARP inhibitors represent one of the successful models of translational research in this area and clinical data showed high efficacy and reasonable toxicity with these agents in patients with breast cancer and BRCA mutation. Recent studies have underlined that some subtypes of breast cancer are highly immunogenic. Promising activity has been shown with immunotherapeutic agents particularly in DDR deficient breast cancers. Chemotherapeutics, DNA repair pathway inhibitors and immunotherapies might result in further improved outcomes in certain subsets of patients with breast cancer and DDR.