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The target article proposed that women display greater self-protectiveness than men to major physical and social threats because such self-protective responses have higher fitness value for women than men. Rather than having evolutionary roots, we suggest the various physiological, behavioral, and emotional responses to social and physical threats exhibited more by women than men are instead rooted in sociocultural forces.

Purpose: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer. Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene. Results: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively. Conclusions: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening. See related commentary by Kuhl and Schrading, p. 1693

Word frequency is an important predictor of lexical-decision task performance. The current study further examined the role of this variable by exploring the influence of frequency trajectory. Frequency trajectory is measured by how often a word occurs in childhood relative to adulthood. Past research on the role of this variable in word recognition has produced equivocal results. In the current study, words were selected based on their frequencies in Grade 1 (child frequency) and Grade 13 (college frequency). In Experiment 1, four frequency trajectory conditions were factorially examined in a lexical-decision task with English words: high-to-high (world), high-to-low (uncle), low-to-high (brain) and low-to-low (opera). an interaction between Grade 1 and college frequency demonstrated that words in the low-to-high condition were processed significantly faster and more accurately than words in the low-to-low condition, whereas the high-to-high and high-to-low conditions did not differ significantly. In Experiment 2, an advantage for words with an increasing frequency trajectory was also supported in regression analyses on both lexical decision and naming times for 3,039 items selected from the English Lexicon Project (Balota et al., 2007). This was replicated in Experiment 3, based on a regression analysis of 2,680 words from the British Lexicon Project (BLP; Keuleers, Lacey, Rastle, & Brysbaert, 2012). In all analyses, rated age-of-acquisition also significantly impacted word recognition. Together, the results suggest that the age at which a word is initially learned as well as its frequency trajectory across childhood impact performance in the lexical-decision task. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Treatment of advanced breast cancer remains challenging. Copper and some of the copper-dependent proteins are emerging therapeutic targets because they are essential for cell proliferation and survival, and have been shown to stimulate angiogenesis and metastasis. Here, we show that DCAC50, a recently developed small-molecule inhibitor of the intracellular copper chaperones, ATOX1 and CCS, reduces cell proliferation and elevates oxidative stress, triggering apoptosis in a panel of triple-negative breast cancer (TNBC) cells. Inhibition of ATOX1 activity with DCAC50 disrupts copper homeostasis, leading to increased copper levels, altered spatial copper redistribution, and accumulation of ATP7B to the cellular perinuclear region. The extent and impact of this disruption to copper homeostasis vary across cell lines and correlate with cellular baseline copper and glutathione levels. Ultimately, treatment with DCAC50 attenuates tumor growth and suppresses angiogenesis in a xenograft mouse model, and prevents endothelial cell network formation in vitro. Co-treatment with paclitaxel and DCAC50 enhances cytotoxicity in TNBC and results in favorable dose reduction of both drugs. These data demonstrate that inhibition of intracellular copper transport targets tumor cells and the tumor microenvironment, and is a promising approach to treat breast cancer.