Sexual health after a breast cancer diagnosis in young women: clinical implications for patients and providers.

PURPOSE: Sexual dissatisfaction after breast cancer treatment is a common phenomenon that, unfortunately, places a significant strain on young women and is becoming more common as treatment regimens rely more and more on anti-endocrine therapies. METHODS: A PubMed review of peer reviewed manuscripts between the years 1998-2020 evaluating sexual health and wellbeing in cancer patients, primarily young women with breast cancer, was conducted. RESULTS: There are several categories of sexual dissatisfaction women may experience as a result of her breast cancer diagnosis, including menopausal symptoms and dyspareunia, negative body image, reduced sexual desire, strained relationships and partner communication, and anxiety about cancer disclosure in dating relationships. Several methods of addressing each domain have been studied. While hormonal replacement therapy remains controversial, other medication regimens have been shown to be effective in treating menopausal symptoms and dyspareunia. Cognitive behavioral therapy, sex therapy, and couples' therapy are all effective in addressing a variety of symptoms across multiple domains. CONCLUSIONS: Oncologists are often not prepared to discuss sexual health concerns as frequently as women need. Further work is needed to bring easily digestible and meaningful educational opportunities into clinical practice so young breast cancer survivors can receive comprehensive post-cancer survivorship care.

Immune evasion of dormant disseminated tumor cells is due to their scarcity and can be overcome by T cell immunotherapies.

The period between "successful" treatment of localized breast cancer and the onset of distant metastasis can last many years, representing an unexploited window to eradicate disseminated disease and prevent metastases. We find that the source of recurrence-disseminated tumor cells (DTCs) -evade endogenous immunity directed against tumor neoantigens. Although DTCs downregulate major histocompatibility complex I, this does not preclude recognition by conventional T cells. Instead, the scarcity of interactions between two relatively rare populations-DTCs and endogenous antigen-specific T cells-underlies DTC persistence. This scarcity is overcome by any one of three immunotherapies that increase the number of tumor-specific T cells: T cell-based vaccination, or adoptive transfer of T cell receptor or chimeric antigen receptor T cells. Each approach achieves robust DTC elimination, motivating discovery of MHC-restricted and -unrestricted DTC antigens that can be targeted with T cell-based immunotherapies to eliminate the reservoir of metastasis-initiating cells in patients.

Clinicopathologic Characteristics, Treatment Outcomes, and Acquired Resistance Patterns of Atypical EGFR Mutations and HER2 Alterations in Stage IV Non-Small-Cell Lung Cancer.

BACKGROUND: The clinicopathologic characteristics, acquired resistance patterns, and outcomes among patients with atypical EGFR mutations and HER2 alterations remain underexplored. PATIENTS AND METHODS: A single-center retrospective review was conducted. Oncogenes assessed include typical EGFR (t-EGFR; exon 19 del and L858R), atypical EGFR (a-EGFR; G719X, exon 20, L861Q), HER2 (exon 19, exon 20, amplifications), gene fusions (ALK, ROS1, RET), RAS (KRAS, NRAS), and RAF (BRAF V600E). Progression-free survival (PFS), overall survival (OS), disease control rate, and objective response rate (Response Evaluation Criteria in Solid Tumors 1.1) were collected. RESULTS: Among 570 patients, we found 55 a-EGFR mutations (13 G719X, 38 exon 20, 4 L861Q) and 31 HER2 alterations (2 exon 19 mutations, 27 exon 20 insertions, 2 amplifications). Patients with EGFR and HER2 alterations had increased lung and bone metastases relative to patients with gene fusions, RAS/RAF mutations, and no identified driver oncogenes (P < .001). Patients with EGFR exon 20 insertions had a median PFS to EGFR tyrosine kinase inhibitors (TKIs) of 5 months and an OS of 16 months-significantly worse than exon 19 del and L858R (Bonferroni correction; P < .001), but not G719X or L861Q. Relative to t-EGFR mutations, T790M and MET amplification occurred less frequently as acquired resistance mechanisms among a-EGFR samples (P < .001). Ten patients with a-EGFR mutations and HER2 alterations received single-agent immune checkpoint inhibitors (ICIs) with no radiographic responses and a median PFS of 2 months. CONCLUSION: EGFR and HER2-mutated NSCLC have a high rate of synchronous lung and bone metastases. Patients with a-EGFR mutations have inferior responses to EGFR-directed therapies with lower rates of acquired T790M and MET amplification. Responses to ICIs are uniformly poor. Novel therapeutic approaches are needed.

Survival Outcomes of Radical Prostatectomy Versus Radiotherapy in Intermediate-Risk Prostate Cancer: A NCDB Study.

BACKGROUND: Studies of various prostate cancer patient cohorts found men receiving external-beam radiotherapy (EBRT) had higher mortality than men undergoing radical prostatectomy (RP). Conversely, a recent clinical trial showed no survival differences between treatment groups. We used the National Cancer Data Base (NCDB) to evaluate overall survival in intermediate-risk (T2b-T2c or Gleason 7 [grade group II or III] or prostate-specific antigen 10-20 ng/mL) prostate cancer patients undergoing EBRT with or without androgen deprivation therapy (ADT), RP, or no initial treatment. PATIENTS AND METHODS: We analyzed 268,378 men with intermediate-risk prostate cancer from 2004 to 2012. Kaplan-Meier estimates and multivariable Cox proportional hazards models were used to compare survival between treatments. RESULTS: After adjusting for patient and facility covariables, men receiving no initial treatment averaged greater adjusted mortality risk than men receiving EBRT (hazard ratio [HR], 1.71; 95% confidence interval [CI] 1.62-1.80; P < .001), EBRT + ADT (HR, 1.73; 95% CI 1.64-1.81; P < .001), or RP (HR, 4.18; 95% CI 3.94-4.43; P < .001). Men undergoing RP had significantly lower adjusted mortality risk than men receiving either EBRT (HR, 0.41; 95% CI 0.39-0.43; P < .001) or EBRT + ADT (HR, 0.41; 95% CI 0.39-0.43; P < .001). No difference was observed between men receiving EBRT or EBRT + ADT (HR, 1.01; 95% CI 0.97-1.05; P = .624). CONCLUSION: Men treated with RP experienced significantly lower overall mortality risk than EBRT with or without ADT and no treatment patients, regardless of patient, demographic, or facility characteristics. The results are limited by the lack of cancer-specific mortality in this database.

Anxiety and depression: Easing the burden in COPD patients.

Anxiety and depression are common comorbidities of COPD. The simple evaluation tools and therapy options described here can help improve patients' quality of life.

Lysophosphatidic Acid Stimulates Urokinase Receptor (uPAR/CD87) in Ovarian Epithelial Cancer Cells.

BACKGROUND/AIM: Lysophosphatidic acid (LPA) is a bioactive lipid positively linked with ovarian cancer progression. The multi-functional urokinase receptor (uPAR), a cell-surface glycoprotein, binds and facilitates activation of uPA and laterally regulates integrin and tyrosine kinase receptor activities in promotion of cell migration and invasion. We hypothesized that LPA stimulates uPAR expression and activity in ovarian epithelial cancer cells. MATERIALS AND METHODS: Ovarian epithelial cancer cell lines OVCA 429 and OVCA 433 were stimulated with LPA and examined for uPAR mRNA expression and protein localization. uPA binding to OVCA plasma membranes was measured through enzymatic analysis of affinity-isolated cell-surface proteins. RESULTS: LPA drove cell-surface uPAR aggregation and mRNA expression concomitant with increased cell-surface binding of uPA. Both control and LPA-stimulated uPAR expression and uPA cell-surface association involved phosphatidylinositol 3-kinase, but not p38 or p42 mitogen-activated protein kinase, signaling. CONCLUSION: These data provide mechanistic insight into ovarian epithelial cancer cell progression by demonstrating that LPA drives uPAR expression and uPA binding.