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In mammalian cells, DNA damage response initiates repair by error-free homologous recombination (HRR) or by error-prone non-homologous end joining (NHEJ). DNA damage is detected by PARP proteins that facilitate this repair, both in normal cells and in cancer cells. Cells containing BRCA1/2 mutations have an HRR-deficient repair mechanism which may result in unrepaired one-ended double-strand breaks and stalled replication forks, considered as the most lethal cell damage. Here, we review the state of the art of the role of Poly (ADP-ribose) polymerase (PARP) inhibitors as a precision-targeted anticancer drug in BRCA1/2-mutated female breast cancer. Although knowledge is incomplete, it is assumed that the main role of the archetype PARP1 in the cell nucleus is to detect and adhere to single-strand breaks. This mediates possible damage repair, after which cells may continue replication; this process is called synthetic lethality. As for PARP clinical monotherapy, progression-free survival has been observed using the FDA- and EMA-approved drugs olaparib and talazoparib. In the case of combined drug therapy, a synergy has been demonstrated between veliparib and platinum drugs. Information regarding adverse effects is limited, but hematological effects have been described. However, there is need for multicenter trials, preferably conducted without commercial guidance and funding. Some of the available trials reported resistance to PARP inhibitors. In this review, we also describe the various causes of resistance to PARP inhibitors and research indicating how resistance can be overcome. [ABSTRACT FROM AUTHOR]

Screening mammography offers the possibility of discovering malignant diseases at an early stage, which is consequently treated early, thereby reducing the mortality rate. However, ionizing radiation as used in low-dose X-ray mammography may be associated with a risk of radiation-induced carcinogenesis. In the context of the harmful effects of ionizing radiation, this article reviewed novel radiobiological data and provided a simulation of the relative incidence of radiation-induced breast cancer due to screening against a background baseline incidence in a population of 100,000 individuals. The use of modern digital mammographic technology was assumed, giving rise to a glandular dose of 2.5 mGy from a 2-view per breast image. Assuming no latency time, this led to a ratio of induced incidence rate over baseline incidence rate of about 1.6? for biennial screening in women aged 50-74 years, although it cannot be excluded that the dose and dose rate effectiveness factor values relying on new radiobiological insights may lower this number to about 0.7?. This carcinogenic risk is considered small in relation to the potential beneficial effects of screening, especially as latency time was not taken into consideration. However, individuals who are known to be carriers of risk-increasing genetic variations and/or have an inherited disposition of breast cancer should avoid ionizing radiation as much as possible and should be referred to ultrasound or magnetic resonance imaging. In addition, a significant, but difficult to quantify, risk of cancer is present for individuals who suffer from hypersusceptibility to ionizing radiation. [ABSTRACT FROM AUTHOR]

Over the past two decades technical advances and improvements have made computed tomography (CT) a valuable and essential tool in the array of diagnostic imaging modalities. CT uses ionizing radiation (X-rays) which may damage DNA and increase the risk of carcinogenesis. This is especially pertinent in pediatric CT as children are more radiosensitive and have a longer life expectancy than adults. The purpose of this paper is to review and elucidate the potential harmful effects of ionizing radiation in terms of solid cancer induction from pediatric CT scanning. In the light of scientific and technical developments, we will also discuss the possible strategies and ongoing efforts to reduce CT radiation exposure in pediatric patients. In this context, we will not ignore the fact that a well-justified CT scan may exceed its risk and have a favorable impact. [ABSTRACT FROM AUTHOR]