No abstract

Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life. Methods: Our search included PubMed, ASCO, ESMO and SABCS databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects. Results: Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12-1.93, p = 0.005], vomiting was 1.74 (95% CI: 1.09-2.76, p = 0.02), decreased appetite was 1.42 (95% CI: 1.07-1.88, p = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19-1.74, p = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29-4.13, p = 0.89), vomiting was 1.38 (95% CI: 0.25-7.75, p = 0.72), decreased appetite was 4.00 (95% CI: 0.87-18.37, p = 0.07), and highgrade diarrhea was 1.19 (95% CI: 0.44-3.21, p = 0.73). Conclusion: Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy.

Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all-grade and high-grade hematological adverse events, which seems to be a class-effect, but not of febrile neutropenia compared with hormonal therapy alone.

CDK4/6 inhibitors were associated with an increased risk of fatigue, alopecia and stomatitis. Further studies with self-reported questionnaires may elucidate the impact of the increased risk of these selected adverse effects on the patients' quality of life.

Background Contrast-enhanced mammography (CEM) has been discovered to be more sensitive and specific than two-dimensional full-field digital mammography (FFDM) in both screening and diagnostic settings. The aim of the study was to assess the additive role of CEM in the detection and characterization of breast lesions in women with increased risk of developing breast cancer. This prospective study included 283 female patients with increased risk of developing breast cancer (i.e., positive family history of breast cancer, personal history of breast cancer, and heterogeneously dense mammary parenchyma) coming for either screening (n = 127/283 (49.1%)) or diagnostic (n = 156/283 (55.1%)) purpose. All patients had FFDM and CEM done, and the findings were evaluated independently; final Breast Imaging Reporting And Data System (BIRADS) classification was given for each modality. Results were then compared with histopathology or ultrasound findings with routine follow-up for normal and typically benign findings. Results In this study, 283 women with mean age of 48 were enrolled. Among the studied cases regardless to a specific risk factor, 15/283 (5.3%) were diagnosed as normal, 13/283 (4.6%) as inflammatory lesions, 72/283(25.4%) as benign lesions, 6/283 (2.1%) as benign precancerous lesions, and 177/283 (62.5%) as malignant. The overall sensitivity and specificity of the CEM were 92.7 and 71.43 %, respectively, while FFDM were 80.90 and 59.05%, respectively. Conclusion Contrast-enhanced mammography is a valuable screening and diagnostic imaging modality in patients with increased risk of developing breast cancer with diagnostic indices higher than mammography resulting in a significantly higher cancer detection rate.