Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and confer worse prognosis in breast cancer patients. The inhibitors targeting three key nodes of these pathways, PI3K, AKT and mTOR, are continuously developed. For breast cancer patients to truly benefit from PAM pathway inhibitors, it is necessary to clarify the frequency and mechanism of abnormal alterations in the PAM pathway in different breast cancer subtypes, and further explore reliable biomarkers to identify the appropriate population for precision therapy. Some PI3K and mTOR inhibitors have been approved by regulatory authorities for the treatment of specific breast cancer patient populations, and many new-generation PI3K/mTOR inhibitors and AKT isoform inhibitors have also been shown to have good prospects for cancer therapy. This review summarizes the changes in the PAM signaling pathway in different subtypes of breast cancer, and the latest research progress about the biomarkers and clinical application of PAM-targeted inhibitors.

To date, there has been limited information on phytoestrogen (PE) exposure and metabolism in breastfed infants. In the present work, 50 sample pairs of Chinese breastfed infants’ urine and the corresponding breast milk were collected. The contents of the relevant PE metabolites in the biosamples were detected via liquid chromatography–tandem mass spectrometry. The correlations between the PE metabolite contents in breastfed infants’ urine and those in the corresponding breast milk were analyzed. The average concentrations of total PE metabolites in breast milk and urine were 0.27 and 0.23 nmol/mL, respectively. Genistein and enterolactone levels in the infant urine were positively correlated with their concentrations in the corresponding breast milk samples, which implies that urine excretion can be utilized as a noninvasive parameter for precise genistein and enterolactone intake assessment. Additionally, the efficiency of PE urine excretion showed significant differences across infants with different ages, genders, and durations of pregnancy.

BackgroundThere is lack of large-scale real-world research evidence showing the impact of endocrine therapy on blood lipids in Chinese breast cancer patients, especially those with premenopausal breast cancer. Based on a large breast cancer cohort at West China Hospital, we aimed to compare the risk of dyslipidemia between premenopausal and postmenopausal women based on the endocrine therapy used.MethodsA total of 1,883 early-stage breast cancer (EBC) patients who received endocrine monotherapy [selective estrogen receptor modulator (SERM) and aromatase inhibitor (AI), with or without ovarian function suppression] with normal blood lipid levels at baseline were retrospectively included between October 2008 and April 2017. Dyslipidemia was defined as an abnormality in cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein, and total cholesterol (TC) levels. The risk accumulation function was used to calculate the incidence of dyslipidemia in order to assess the absolute risk, while the multivariate Cox regression model was used to calculate the relative risk of dyslipidemia between the groups.ResultsPatients with EBC were followed up for 60 months to monitor their blood lipid levels. The accumulated 5-year incidence of dyslipidemia in postmenopausal patients was higher than that in premenopausal patients (adjusted HR [95% confidence interval], 1.25 [1.01–1.56], 41.7% vs. 31.2%, p = 0.045). In premenopausal patients, the risk of abnormal TC was significantly higher in the OFS+AI group compared with that in the SERM group (adjusted HR [95% CI], 6.24 [3.19–12.20], p < 0.001, 5-year abnormal rates: 21.5% vs. 2.4%), and that of abnormal LDL-C level also increased (adjusted HR [95% CI], 10.54 [3.86–28.77], p < 0.001, 5-year abnormal rates: 11.1% vs. 0.9%). In postmenopausal patients, the risk of abnormal TC or LDL-C levels showed a similar trend in the AI and SERM groups.ConclusionsIn addition to postmenopausal patients, dyslipidemia is also common in premenopausal Chinese patients with EBC who received endocrine therapy. Irrespective of menopausal status, AI treatment increases the risk of TC/LDL-C dyslipidemia than SERM treatment.

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