Cortical and subcortical morphological alterations in postpartum depression.

Postpartum depression (PPD) is the most common postpartum psychiatric disorder, which can negatively affect both mothers and their offspring. Although the functional changes of PPD have been extensively studied, little is known about its structural abnormalities. This study aimed to examine the cortical and subcortical morphological abnormalities in PPD. High resolution T1 structural MRI data of 29 PPD women and 23 matched healthy postpartum women (HPW) were included in this study. Using surface-based morphometry, we examined the differences between the PPD and HPW group in the cortical thickness, local gyrification index and shape changes of deep gray matter nuclei. Compared with the HPW group, women with PPD showed significantly increased cortical thickness in the left superior frontal gyrus, cuneus and right lingual gyrus and fusiform gyrus, which correlated marginally with the EPDS scores of these subjects. In addition, women with PPD showed significant regional inflation in the right pallidum compared with the HPW group. These findings provided further evidence for the structural brain abnormalities in PPD.

Chemotherapy Modulates Endocrine Therapy-Related Resistance Mutations in Metastatic Breast Cancer.

PURPOSE: Accumulation of PIK3CA, ESR1, and GATA3 mutations results in resistance to endocrine therapy in breast cancer patients; however, the response of these genes to chemotherapy is unclear. Therefore, we sought to evaluate the genetic response of circulating tumor DNA (ctDNA) to chemotherapy in metastatic breast cancer patients. METHODS: The mutation frequency of 1021 genes was examined prior to chemotherapy in ctDNA of 44 estrogen receptor-positive metastatic breast cancer patients. These genes were evaluated again in a subset of patients (n=24) following chemotherapy. Mutation frequency was defined as the percentage of mutations found in ctDNA compared to total cell-free DNA. RESULTS: Prior to chemotherapy, PIK3CA was the most commonly mutated gene, with mutation found in 22 of the metastatic breast cancer patients. Following chemotherapy, 16 patients exhibited progressive disease (PD), and 8 patients experienced no progression (non-PD). PIK3CA mutation frequency increased in 56.25% (9/16) of the PD patients but decreased in 62.5% (5/8) of the non-PD patients. As a result, more PD patients exhibited increased PIK3CA mutation frequency than non-PD patients (56.25% vs 0%, P=.002). Further, ESR1 and GATA3 mutations correlated with PIK3CA mutation. Interestingly, patients receiving the mTOR inhibitor everolimus exhibited a lower progression rate (0% vs 62.5%, P=.001), and the combination of everolimus and chemotherapy effectively suppressed PIK3CA, ESR1, and GATA3 gene mutations. CONCLUSION: Together, these results suggest that mTOR inhibition may be a useful chemotherapy adjuvant to suppress chemotherapy-induced gene mutations that render tumors resistant to endocrine therapy in metastatic breast cancer patients with PD.

Inducing or Preventing Subsequent Malignancies for Breast Cancer Survivors? Double-edged Sword of Estrogen Receptor and Progesterone Receptor.

INTRODUCTION: Hormone receptor and human epidermal growth factor receptor 2 (HER2) status is important for breast cancer (BC) treatment. Previous studies have shown that the long-term treatment outcomes of BC are significantly impaired by the development of subsequent malignancies. Therefore, in the present study, we evaluated the effect of hormone receptor/HER2 status on subsequent malignancies in breast cancer survivors. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results*Stat database (8.3.4) was used as the data source. We identified 535,941 female survivors with first primary BC through the database from 1973 to 2013. Of these patients, 23,964 had developed subsequent contralateral BC, 8398 had developed subsequent uterine or ovarian cancer, and 7435 patients had developed subsequent colorectal cancer. RESULTS: Estrogen receptor (ER) positivity and progesterone receptor (PR) positivity were significant protective factors against subsequent BC and ovarian cancer. However, ER+ BC and PR+ BC were significant risk factors for subsequent colorectal cancer. In addition, HER2+ status demonstrated a marginally significant risk effect for subsequent thyroid cancer. Triple-negative (ER-/PR-/HER2-) status showed elevated risk of subsequent breast, ovarian, and uterine cancer. CONCLUSION: ER+/PR+ patients were less likely develop secondary breast and ovarian malignancies, possibly owing to advancements in anti-ER/PR treatment. However, ER+/PR+ patients were more likely to develop colorectal cancer, suggesting a potential screening necessity for these patients.

Identifying Circulating Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance.

PURPOSE: In cancer patients, tumor gene mutations contribute to drug resistance and treatment failure. In patients with metastatic breast cancer (MBC), these mutations increase after multiline treatment, thereby decreasing treatment efficiency. The aim of this study was to evaluate gene mutation patterns in MBC patients to predict drug resistance and disease progression. METHOD: A total of 68 MBC patients who had received multiline treatment were recruited. Circulating tumor DNA (ctDNA) mutations were evaluated and compared among hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) subgroups. RESULTS: The baseline gene mutation pattern (at the time of recruitment) varied among HR/HER2 subtypes. BRCA1 and MED12 were frequently mutated in triple negative breast cancer (TNBC) patients, PIK3CA and FAT1 mutations were frequent in HR+ patients, and PIK3CA and ERBB2 mutations were frequent in HER2+ patients. Gene mutation patterns also varied in patients who progressed within either 3 months or 3-6 months of chemotherapy treatment. For example, in HR+ patients who progressed within 3 months of treatment, the frequency of TERT mutations significantly increased. Other related mutations included FAT1 and NOTCH4. In HR+ patients who progressed within 3-6 months, PIK3CA, TP53, MLL3, ERBB2, NOTCH2, and ERS1 were the candidate mutations. This suggests that different mechanisms underlie disease progression at different times after treatment initiation. In the COX model, the ctDNA TP53 + PIK3CA gene mutation pattern successfully predicted progression within 6 months. CONCLUSION: ctDNA gene mutation profiles differed among HR/HER2 subtypes of MBC patients. By identifying mutations associated with treatment resistance, we hope to improve therapy selection for MBC patients who received multiline treatment.