Sex and gender may influence the epidemiology, pathogenesis, and prognosis of cancer. This narrative review describes sex and gender differences in the epidemiology and pathogenesis of cancer, and how such differences may impact the pharmacodynamics and pharmacokinetics of cancer treatment. For most types of cancer unrelated to reproductive function, incidence is higher in males than in females, except for gallbladder and thyroid cancers, which are much more common in women. Cancer mortality is higher in men than women; women account for a larger proportion of survivors. These differences may be related to biological differences in pathogenesis or differences in behaviors relating to cancer risk or detection. The pharmacokinetics and pharmacodynamics of cancer therapies also differ between sexes due to differences in body composition, physiology, and receptor expression. Overall, sex and gender are essential variables to be considered in research and clinical practice, influencing diagnosis, subtyping (biomarkers), prognostication, treatment, and dosage.

Polymorphisms in the metabolism, detoxification or DNA repair pathways have been proposed as potential predictors of response to 5-fluorouracil and oxaliplatin. We have studied the predictive value of a set of germline genetic polymorphisms in metastatic colorectal cancer patients treated with mFolfox-6. A total of 72 patients, comprising 50 men (69.4%) and 22 women (30.6%), were included after the signing of an informed consent form. Median age was 65.5 years (range: 32-80). All participants received mFolfox-6. DNA was extracted from peripheral blood samples and genotyped by direct sequencing, SnapShot(®) and multiplex PCR techniques. Eight polymorphisms within six genes were investigated: TS 5´-UTR (variable number tandem repeat + G/C), TS 3´-UTR (TS1494del6); MTHFR C677T and A1298C; GSTP1 I105V; ERCC1 C118T; XPD Lys751Gln and XRCC1 Arg399Gln. Association was evaluated by univariate analysis, and Cox regression and Kaplan-Meier assessed survival. The local ethics committee approved the pharmacogenetic study protocol and all subjects signed an informed consent before participating in the study. The sample was in Hardy-Weinberg equilibrium. Only XPD Lys751Gln was found to be significantly associated with a favorable progression-free survival (PFS). Median PFS for XPD Lys751Gln patients (n = 33) was 16 months (95% CI: 9.2-22.7), 10 months (95% CI: 6.1-13.9) for Gln/Gln (n = 11) and 8 months (95% CI: 5.8-10.2) for Lys/Lys (n = 28), p = 0.019. The increased risk of progression was: 1.93 (95% CI: 1.13-13.30; p = 0.017) for Lys/Lys and 2.1 (95% CI: 1.01-4.22; p = 0.047) for Gln/Gln. Patients with one or two Val alleles of GSTP1 tended to a lower risk of progression compared with Ile/Ile homozygotes, p = 0.067. When XPD Lys751Gln and GSTP1 were analyzed jointly, patients who carried one or two favorable genotypes, XPD Lys751Gln and Val, had a longer median PFS: 11 months (95% CI: 7.4-14.6) compared with six (95% CI: 4.6-7.4) with unfavorable genotypes, p < 0.001. In metastatic colorectal cancer patients treated with mFolfox-6, the combination of haplotype XPD Lys751Gln-GSTP1 105Val seems to predict the risk of progression.

Medication adherence is directly associated with health outcomes. Adherence has been reviewed extensively; however, most studies provide a narrow scope of the problem, covering a specific disease or treatment. This project’s objective was to identify risk factors for non-adherence in the fields of rheumatology, oncology, and cardiology as well as potential interventions to improve adherence and their association with the risk factors. The project was developed in three phases and carried out by a Steering Committee made up of experts from the fields of rheumatology, oncology, cardiology, general medicine, and hospital and community pharmacy. In phase 1, a bibliographic review was performed, and the articles/reviews were classified according to the authors’ level of confidence in the results and their clinical relevance. In phase 2, 20 risk factors for non-adherence were identified from these articles/reviews and agreed upon in Steering Committee meetings. In phase 3, potential interventions for improving adherence were also identified and agreed upon. The results obtained show that adherence is a dynamic concept that can change throughout the course of the disease, the treatments, and other factors. Educational interventions are the most studied ones and have the highest level of confidence in the authors’ opinion. Information and education are essential to improve adherence in all patients.

Differences between the biological sexes have long been observed in cancer incidence and prevalence, and in treatment outcomes including efficacy and toxicity. Ideally, there should be sufficient information to improve the individualization of cancer treatment by incorporating sex into treatment decisions. Necessary information should include: the nature and source of these differences; whether inherent to the specific cancer (such as molecular profiles, metabolic behaviors, and immune responses); the pathophysiological mechanisms of the specific cancer; or the pharmacokinetic and pharmacodynamic profiles of different cancer drugs. The influence of gender, which is defined as the sociocultural construct that determines societal norms for males and females, should also be included in personalized decision-making. This review aimed to describe the current evidence on the impact of sex and gender on treatment effects, outcomes, and toxicity profiles in cancer patients. Data for the influence of gender were negligible, whereas clinical studies and meta-analyses in different cancer types have identified differences between males and females in the effectiveness on survival outcomes of immunotherapy, chemotherapy, targeted therapy, and radiotherapy. Similarly, toxicity profiles of different cancer treatments varied between sexes. Based on these observed differences, it seems clear that sex should be included as an important variable when individualizing treatment; however, more research into sex- and gender-related differences in cancer treatment efficacy and toxicity, and the causes for these differences, is required before this can be fully incorporated into individualized treatment programs in real-world clinical practice.