Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine.

Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. We aim systematically promote this intervention with all Lynch syndrome carriers.

Fertility counseling in women with hereditary cancer syndromes.

Hereditary cancer syndromes are a heterogeneous group of genetic conditions that are associated with an increased risk of developing cancer during lifespan. In affected women, parenthood may be accompanied by concerns for the offspring, considering the common autosomal dominant inheritance. Moreover, fertility preservation to prevent the detrimental effects of cancer treatments differs compared to other clinical contexts. The necessity to preserve gametes is indeed predictable and expected to be common. For these reasons, we advocate a personalized and early fertility counseling. Carriers should be aware of the risk of transmission. The possibility to perform elective oocytes cryopreservation, either before (previvors) or after (survivors) cancer diagnosis should be discussed. Finally, they should be informed about the options of preimplantation genetic test (PGT) and oocytes donation. In conclusion, physicians engaged in oncofertility should personalize the counseling for women with hereditary cancer syndromes, being aware of their peculiar needs.