In the past 20 years, clinicians have shifted away from relying solely on clinicopathologic indicators toward increasing use of multigene expression assays in guiding treatment decisions regarding adjuvant chemotherapy for early-stage hormone receptor (HR)-positive, HER2-negative breast cancer. Oncotype DX Recurrence Score (RS) is one of the most widely used multigene assays when considering indications for adjuvant chemotherapy, and guidelines have recently incorporated its use in women with early HR-positive HER2-negative breast cancer and up to three positive lymph nodes. While multiple retrospective and prospective clinical studies have demonstrated that most women with a low- to mid-range RS (0-25) can safely forgo chemotherapy, premenopausal women remain an important subgroup for which recommendations based on RS are ill-defined. The majority of patients included in clinical trials and retrospective analyses validating the use of RS have been postmenopausal women. In the subgroup of premenopausal women with HR-positive HER2-negative breast cancer, studies indicate that traditional clinicopathologic methods for assessing risk continue to be powerful tools when combined with RS to predict benefit from chemotherapy. This suggests that there is an element of uncaptured risk inherent to the premenopausal state that evades characterization by RS alone. This review describes the evidence that has supported the recommendation of RS in clinical guidelines, specifically focusing on data for its current use in premenopausal women. We review available data regarding the impact of the menstrual cycle on hormonally regulated gene expression, which may drive variations in the RS. Further research on the reliability and interpretation of the RS in the premenopausal subgroup is necessary and represents a gap in knowledge of how the RS should be applied in premenopausal women.

The development of genetically encoded dopamine sensors such as dLight has provided a new approach to measuring slow and fast dopamine dynamics both in brain slices and in vivo, possibly enabling dopamine measurements in areas like the dorsolateral striatum (DLS) where previously such recordings with fast-scan cyclic voltammetry (FSCV) were difficult. To test this, we first evaluated dLight photometry in mouse brain slices with simultaneous FSCV and found that both techniques yielded comparable results, but notable differences in responses to dopamine transporter inhibitors, including cocaine. We then used in vivo fiber photometry with dLight in mice to examine responses to cocaine in DLS. We also compared dopamine responses during Pavlovian conditioning across the striatum. We show that dopamine increases were readily detectable in DLS and describe transient dopamine kinetics, as well as slowly developing signals during conditioning. Overall, our findings indicate that dLight photometry is well suited to measuring dopamine dynamics in DLS.

Immuno-oncology (IO) and targeted therapies, such as small molecule inhibitors, have changed the landscape of cancer treatment and prognosis; however, durable responses have been difficult to achieve due to tumor heterogeneity, development of drug resistance, and adverse effects that limit dosing and prolonged drug use. To improve upon the current medicinal armamentarium, there is an urgent need for new ways to understand, reverse, and treat carcinogenesis. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 is a powerful and efficient tool for genome editing that has shown significant promise for developing new therapeutics. While CRISPR/Cas9 has been successfully used for pre-clinical cancer research, its use in the clinical setting is still in an early stage of development. The purpose of this review is to describe the CRISPR technology and to provide an overview of its current applications and future potential as cancer therapies.