Risk of recurrence and pregnancy outcomes in young women with breast cancer who do and do not undergo fertility preservation.

PURPOSE: To assess the impact of fertility preservation (FP) requiring ovarian stimulation on breast cancer outcomes and pregnancy after breast cancer. METHODS: Women aged ≤ 40 years diagnosed with stage I-III breast cancer between 2007 and 2018 and referred for FP consultation prior to systemic therapy were identified from a British Columbia fertility center database. The primary endpoint was invasive breast cancer-free survival (iBCFS) and secondary endpoints were overall survival (OS) and achievement of pregnancy. Survival and pregnancy endpoints were compared using Cox and logistic regression analyses, respectively, for patients who did and did not undergo FP. RESULTS: The study included 153 patients, with 71 (46%) in the FP group and 82 (54%) in the non-FP group. Patients who underwent FP were more likely to be ECOG 0 (99% vs. 88%, p = 0.011) and receive chemotherapy (93% vs. 67%, p < 0.001), but had similar ER positivity status to non-FP patients (70% vs. 79%, p = 0.21). Over a median follow-up of 4.1 years, there were no differences in iBCFS (HR 1.006, 95% CI 0.416-2.438, p = 0.988) or OS (HR 0.789, 95% CI 0.210-2.956, p = 0.725) between FP and non-FP groups. Patients who underwent FP had higher odds of conceiving at least once (OR 3.024, 95% CI 1.312-6.970, p = 0.008). CONCLUSION: At a median follow-up of 4.1 years, FP did not impact iBCFS or OS, supporting its safety in young women with breast cancer. In addition, patients who underwent FP were more likely to become pregnant after breast cancer, highlighting the value of pre-oncologic treatment FP in survivorship family planning.

Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA.

The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV. We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV(mac251.) HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.

Advanced breast cancer metastasized in the brain: treatment standards and innovations.

Breast cancer continues to be a difficult disease to treat due to high rates of metastasis. Metastasis to the brain presents a unique and often overlooked challenge. In this focused review, we discuss the epidemiology of breast cancer and which types frequently metastasize to the brain. Novel treatment approaches are highlighted with supporting scientific evidence. The role of the blood-brain barrier and how it may become altered with metastasis is addressed. We then highlight new innovations for Her2-positive and triple-negative breast cancer. Finally, recent directions for luminal breast cancer are discussed. This review serves to enhance understanding of pathophysiology, spark continued innovation, and provide a user-friendly resource through tables and easy-to-process figures.

Ovarian Cancer Metastasis to the Central Nervous System: A Literature Review.

Ovarian cancer is one of the leading causes of cancer-related deaths among women in the United States. Metastasis to the central nervous system has become more frequent in the previous decades, however, treatment options remain limited. In this review, we discuss the pathophysiology of ovarian cancer and how metastasis to the central nervous system typically occurs. We then discuss cases of metastasis presented in the literature to evaluate current treatment regimens and protocols. Finally, we highlight emerging treatment options that are being utilized in clinics to provide personalized treatment therapy for a patient's unique diagnosis. This review aims to further the understanding of pathophysiology, stimulate further innovative treatments, and present accessible resources through tables and figures.

Development of a Geropathology Grading Platform for nonhuman primates.

A geropathology grading platform (GGP) for assessing age-related lesions has been established and validated for in inbred strain of mice. Because nonhuman primates (NHPs) share significant similarities in aging and spontaneous chronic diseases with humans, they provide excellent translational value for correlating histopathology with biological and pathological events associated with increasing age. Descriptive age-associated pathology has been described for rhesus macaques and marmosets, but a grading platform similar to the mouse GGP does not exist. The value of these NHP models is enhanced by considerable historical data from clinical, bio-behavioral, and social domains that align with health span in these animals. Successful adaptation of the mouse GGP for NHPs will include 1) expanding the range of organs examined; 2) standardizing necropsy collection, tissue trimming, and descriptive lesion terminology; 3) expanding beyond rhesus macaques and marmosets to include other commonly used NHPs in research; and 4) creating a national resource for age-related pathology to complement the extensive in-life datasets. Adaptation of the GGP to include translational models other than mice will be crucial to advance geropathology designed to enhance aging research.

Association of early experience with neurodegeneration in aged primates.

Environment influences brain development, neurogenesis and, possibly, vulnerability to neurodegenerative disease. We retrospectively examined the brains of aged rhesus monkeys reared during early life in either small cages or larger, "standard-sized" cages; all monkeys were subsequently maintained in standard-sized cages during adulthood. Aged monkeys reared in smaller cages exhibited significantly greater ß-amyloid plaque deposition in the neocortex and a significant reduction in synaptophysin immunolabeling in cortical regions compared to aged monkeys reared in standard-sized cages (p<0.001 and p<0.05, respectively). These findings suggest that early environment may influence brain structure and vulnerability to neurodegenerative changes in late life.