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Evolution of Angiogenic Factors in Pregnant Patients with Breast Cancer Treated with Chemotherapy.

ABSTRACT: High prevalence of placental-derived complications, such as preeclampsia and intrauterine growth restriction, has been reported in women with breast cancer (BC) treated with chemotherapy during pregnancy (PBC-CHT). To ascertain whether PBC-CHT is associated with an imbalance of angiogenic factors, surrogate markers for placental insufficiency, that could explain perinatal outcomes. Prospective study between 2012 and 2016 in a single institution. Soluble fms-like tyrosine kinase (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng) in maternal blood were assessed throughout pregnancy in 12 women with BC and 215 controls. Cancer patients were treated with doxorubicin-based regimes and with taxanes. Ten PBC-CHT (83%) developed obstetrical complications. At the end of the third trimester, significantly higher levels of sFlt-1; sFlt-1/PGF ratio, and sEng levels were observed in BC women as compared to controls. Moreover; there was a significant correlation between plasma levels of sFlt-1 and the number of chemotherapy cycles administered. Besides, more chemotherapy cycles correlated with lower birthweight and head circumference at birth. Women with BC treated during pregnancy showed an antiangiogenic state compatible with placental insufficiency. Angiogenic factors could be useful in the clinical obstetric management of these patients; although further studies will be required to guide clinical decision-making.

SUBMITTER: Saura C

PROVIDER: S-EPMC7926500 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Evolution of Angiogenic Factors in Pregnant Patients with Breast Cancer Treated with Chemotherapy.

Saura Cristina C Sánchez Olga O Martínez Sandra S Domínguez Carmen C Dienstmann Rodrigo R Ruíz-Pace Fiorella F Céspedes Maria Concepció MC Peñuelas Ángeles Á Cortés Javier J Llurba Elisa E Córdoba Octavi O

Cancers 20210223 4

High prevalence of placental-derived complications, such as preeclampsia and intrauterine growth restriction, has been reported in women with breast cancer (BC) treated with chemotherapy during pregnancy (PBC-CHT).<h4>Aim</h4>To ascertain whether PBC-CHT is associated with an imbalance of angiogenic factors, surrogate markers for placental insufficiency, that could explain perinatal outcomes.<h4>Methods</h4>Prospective study between 2012 and 2016 in a single institution. Soluble fms-like tyrosin ...[more]

PMID: 33672114

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Project description:ObjectivesThis study sought to determine the rate of chemotherapy-related cardiotoxicity and to estimate adherence to recommendations for cardiac monitoring among breast cancer patients treated with chemotherapy.BackgroundHeart failure (HF) is a known complication associated with cancer therapies. Little is known regarding the rate of chemotherapy-related cardiotoxicity and adherence to recommendations for cardiac monitoring among chemotherapy-treated breast cancer patients.MethodsPatients >18 years of age with a diagnosis of nonmetastatic invasive breast cancer between 2009 and 2014, treated with chemotherapy within 6 months of their diagnosis, were identified in the Truven Health MarketScan (IBM Watson Health, Cambridge, Massachusetts) database. HF, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics, Cox proportional hazard regression, and logistic regression.ResultsA total of 16,456 patients were included; the median age was 56 years old. Cardiotoxicity was identified in 4.2% of patients. Therapy with trastuzumab (hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.72 to 2.36) and anthracyclines (HR: 1.53; 95% CI: 1.30 to 1.80), Deyo comorbidity scores (HR: 1.38; 95% CI: 1.15 to 1.66; HR: 2.47; 95% CI: 1.94 to 3.15 for scores of 1 and ≥2, respectively), hypertension (HR: 1.28, 95% CI: 1.09 to 1.51), and valve disease (HR: 1.93; 95% CI: 1.48 to 2.51) were associated with an increased risk of cardiotoxicity. Patients ≤35 years of age (HR: 0.37; 95% CI: 0.19 to 0.72) and 36 to 49 years of age (HR: 0.49; 95% CI: 0.38 to 0.62) were less likely to have cardiotoxicity than patients 65 years of age and older. Among 4,325 patients treated with trastuzumab, guideline-adherent cardiac monitoring was identified in 46.2% of patients. Therapies using anthracyclines (odds ratio [OR]: 1.58; 95% CI: 1.35 to 1.87), taxanes (OR: 1.63; 95% CI: 1.27 to 2.08), and radiation (OR: 1.22; 95% CI: 1.08 to 1.39) were associated with guideline-adherent monitoring.ConclusionsHF is an uncommon complication of breast cancer therapies. The risk was higher among patients treated with trastuzumab or anthracyclines and lower in younger patients. Cardiac monitoring among trastuzumab-treated patients should be a priority among high-risk patients and in the presence of comorbidities or other chemotherapies such as those using anthracyclines.

Project description:Inflammation has been associated with fatigue during and after various types of breast cancer treatments. We examined whether prior chemotherapy was associated with DNA methylation patterns that could explain persisting inflammation and/or fatigue in women treated for breast cancer. Prior to breast radiation therapy, DNA was extracted from peripheral blood mononuclear cells (PBMCs) of 61 Stage 0-IIIA breast cancer patients who had received partial mastectomy with or without chemotherapy. DNA methylation was assessed at >485,000 CpG sites across the genome along with fatigue and plasma inflammatory markers previously associated with fatigue. Compared to non-chemotherapy-treated, women who had received chemotherapy exhibited significantly decreased methylation at eight CpG sites (p<1.03×10(-7)) including four in exon 11 of transmembrane protein 49 (TMEM49), which demonstrated the largest decreases in methylation. Lower methylation at each identified CpG site was associated with increased plasma soluble tumor necrosis factor receptor 2 (sTNFR2) and interleukin (IL)-6 and mediated the relationship between chemotherapy and increases in these inflammatory biomarkers adjusting for multiple clinical and treatment characteristics. sTNFR2, but not CpG methylation status, was correlated with fatigue. Six months after breast radiation therapy, DNA methylation, inflammatory biomarkers and fatigue assessments were repeated in a subset of subjects (N=39). Reduced methylation in 4 of the 8 identified CpG sites was still observed in chemotherapy versus non-chemotherapy-treated patients, albeit with some decay indicating the dynamic and potentially reversible nature of the changes. Reduced methylation in these 4 CpG sites also continued to correlate with either increased sTNFR2 or IL-6, but not fatigue. In conclusion, prior chemotherapy treatment was associated with decreased methylation of CpG sites in DNA from PBMCs of breast cancer patients, which correlated with increased inflammatory markers prior to and 6months after radiation therapy. Persisting epigenetic changes secondary to chemotherapy may be one factor that contributes to inflammation and its consequences including cancer-related fatigue in vulnerable breast cancer patients.

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Evolution of Angiogenic Factors in Pregnant Patients with Breast Cancer Treated with Chemotherapy.

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Evolution of Angiogenic Factors in Pregnant Patients with Breast Cancer Treated with Chemotherapy.

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