Genetic susceptibility to breast cancer increases the risk of neutropenia and agranulocytosis: insights from Mendelian randomization.

PURPOSE: The causal relationship between breast cancer and its estrogen receptor (ER) subtypes and neutropenia and agranulocytosis is unclear. METHODS: In two-sample Mendelian randomization (MR), we used inverse variance weighting (IVW), Bayesian weighted MR (BWMR), MR-Egger, weighted median, simple mode, and weighted mode methods to analyze causality for ER-positive breast cancer, ER-negative breast cancer, overall breast cancer, and drug-induced neutropenia and agranulocytosis. To validate the results, we performed the analysis again using GWAS data on neutropenia from different databases. In multivariable MR (MVMR), we assessed the independent effects of ER-positive and ER-negative breast cancer on causality. RESULTS: Two-sample MR analysis showed a causal relationship between ER-positive breast cancer (IVW odds ratio (OR) = 1.319, P = 7.580 × 10-10), ER-negative breast cancer (OR = 1.285, P = 1.263 × 10-4), overall breast cancer (OR = 1.418, P = 2.123 × 10-13), and drug-induced neutropenia and a causal relationship between ER-positive breast cancer (OR = 1.349, P = 1.402 × 10-7), ER-negative breast cancer (OR = 1.235, P = 7.615 × 10-3), overall breast cancer (OR = 1.429, P = 9.111 × 10-10), and neutropenia. Similarly, ER-positive breast cancer (OR = 1.213, P = 5.350 × 10-8), ER-negative breast cancer (OR = 1.179, P = 1.300 × 10-3), and overall breast cancer (OR = 1.275, P = 8.642 × 10-11) also had a causal relationship with agranulocytosis. MVMR analysis showed that ER-positive breast cancer remained causally associated with drug-induced neutropenia (OR = 1.233, P = 4.188 × 10-4), neutropenia (OR = 1.283, P = 6.363 × 10-4), and agranulocytosis (OR = 1.142, P = 4.549 × 10-3). Heterogeneity analysis and pleiotropy test showed that our results were reliable. CONCLUSION: Our study provides genetic evidence for a causal association between breast cancer and its estrogen receptor subtypes and neutropenia. In clinical practice, in addition to focusing on therapeutic factors, additional attention should be given to breast cancer patients to avoid severe neutropenia.

Effect of adjuvant radiotherapy on overall survival and breast cancer-specific survival of patients with malignant phyllodes tumor of the breast in different age groups: a retrospective observational study based on SEER.

PURPOSE: Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer, with an incidence of less than 1%. The value of adjuvant radiotherapy (RT) for MPTB has been controversial. The aim of the study was to explore the effect of radiotherapy on the long-term survival of female patients with MPTB at different ages. METHODS: Female MPTB patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. A Kaplan-Meier survival analysis was conducted to investigate the value of RT for the long-term survival of MPTB patients in different age groups. Additionally, univariate and multivariate Cox regression analyses were performed for overall survival (OS) and breast cancer-specific survival (BCSS) of MPTB patients. Furthermore, propensity score matching (PSM) was also performed to balance the differences in baseline characteristics. RESULTS: 2261 MPTB patients were included in this study, including 455 patients (20.12%) with RT and 1806 patients (79.88%) without RT. These patients were divided into four cohorts based on their ages: 18-45, 46-55, 56-65, and 65-80. Before adjustment, there was a statistically significant difference in long-term survival between RT-treated and non-RT-treated patients in the younger age groups (age group of 18-45 years: OS P = 0.019, BCSS P = 0.016; age group of 46-55 years: OS P < 0.001, BCSS P < 0.001). After PSM, no difference was found in long-term survival of patients in both younger and older groups regardless of whether they received RT (age group of 18-45 years: OS P = 0.473, BCSS P = 0.750; age group of 46-55 years: OS P = 0.380, BCSS P = 0.816, age group of 56-65 years: OS P = 0.484, BCSS P = 0.290; age group of 66-80 years: OS P = 0.997, BCSS P = 0.763). In multivariate COX regression analysis, RT did not affect long-term survival in patients with MPTB. CONCLUSION: There is no evidence that long-term survival of MPTB patients in specific age groups can benefit from RT.

Effect of radiation therapy on patients with stage T3 or T4 malignant phyllodes tumors: a retrospective observational study based on SEER.

PURPOSE: Among all primary breast tumors, malignant phyllodes tumor of the breast (MPTB) make up less than 1%. In the treatment of phyllode tumors, surgical procedures such as mastectomy and breast-conserving surgery are the mainstay. MPTB has, however, been controversial when it comes to treating it with RT. We aimed to explore the prognostic impact of RT and other clinicopathologic factors on long-term survival for patients with stage T3 or T4 malignant phyllodes tumors. METHODS: We select patients with stage T3 or T4 MPTB who qualified for the criteria between 2000 and 2018 via the Surveillance, Epidemiology, and End Results (SEER) database. We performed 1:1 propensity score matching (PSM) and Kaplan-Meier analysis to explore the role of RT in long-term survival of patients with stage T3 or T4 MPTB. A univariate and multivariate analysis of breast cancer-specific survival (BCSS) and overall survival (OS) risk factors was carried out using a Cox proportional hazards model. In addition, the nomogram graph of OS and BCSS was constructed. RESULTS: A total of 583 patients with stage T3 or T4 malignant phyllodes tumors were included in this study, of whom 154 (26.4%) received RT, and 429 (73.6%) were treated without RT. Before adjustment, between groups with and without RT, BCSS (p = 0.1) and OS (p = 0.212) indicated no significant difference respectively. Using of PSM, the two groups still did not differ significantly in BCSS (p = 0.552) and OS (p = 0.172). In multivariate analysis, age (p < 0.001), surgery of primary site (p < 0.001) and distant metastatic status (p < 0.001) were related to prognosis, while RT still did not affect BCSS (p = 0.877) and OS (p = 0.554). CONCLUSION: Based on the SEER database analysis, the study suggests that the patients with stage T3 or T4 MPTB treated with RT after surgery didn't have significant differences in BCSS or OS compared to those not treated with RT.