Treatments for Breast Cancer That Affect Cognitive Function in Postmenopausal Women

Blaustein, Jeffrey D.

doi:10.1177/2372732217717271

Cited by 11 publications

(13 citation statements)

References 80 publications

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“…Half the marmosets (females: n ϭ 4; males: n ϭ 4) were fed 20 g of letrozole mixed in ϳ0.3 g pudding (Jell-O) daily for 4 weeks. The letrozole dose was determined based on the recommended dose for women (2.5 mg/d) (Bayer et al, 2015). The remaining marmosets (females: n ϭ 3; males: n ϭ 5) received pudding without the drug.…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, attempts were made to match route (i.e., oral) and dose to that of humans. The letrozole dose was determined based on the recommended dose for women (2.5 mg/d) (Bayer et al, 2015). After a 1 week baseline period, half the marmosets (females: n ϭ 4; males: n ϭ 4) were fed 20 g of letrozole mixed in ϳ0.3 g pudding (Jell-O) daily for 4 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Estrogens play an important role in regulating HPC structure and function in both sexes (Frick et al, 2018). Aromatase is expressed in the HPC (Hojo et al, 2004), and AIs have been shown to impact HPC-dependent memory in animals (Tuscher et al, 2016;Bailey et al, 2017) and humans (Collins et al, 2009;Bayer et al, 2015). As a first demonstration of the impact of continuous oral AI use in nonhuman primates, we chose a task that is known to involve this structure.…”

Section: Methodsmentioning

confidence: 99%

“…AIs are associated with side effects that impair quality of life, including insomnia (Desai et al, 2013), hot flashes (Rand et al, 2011), depression (Chumsri et al, 2016, and memory deficits (Bender et al, 2007;Blaustein, 2017; but see Ganz et al, 2016). For example, reduced hippocampal (HPC) activity and increased PFC activity, along with slightly diminished memory, were reported in women taking letrozole (Bayer et al, 2015). Memory deficits in women have also been reported in other studies (e.g., Collins et al, 2009), but not all (for review, see Lee et al, 2016), and one study in older men showed improved spatial memory following AI treatment (Cherrier et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Adverse Effects of Aromatase Inhibition on the Brain and Behavior in a Nonhuman Primate

et al. 2018

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Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side effects, including hot flashes, mood changes, and cognitive impairment. Despite long-term use in humans, little is known about the effects of continuous AI administration on the brain and cognition. We used a primate model of human cognitive aging, the common marmoset, to examine the effects of a 4-week daily administration of the AI letrozole (20 g, p.o.) on cognition, anxiety, thermoregulation, brain estrogen content, and hippocampal pyramidal cell physiology. Letrozole treatment was administered to both male and female marmosets and reduced peripheral levels of estradiol (E2), but unexpectedly increased E2 levels in the hippocampus. Spatial working memory and intrinsic excitability of hippocampal neurons were negatively affected by the treatment possibly due to increased hippocampal E2. While no changes in hypothalamic E2 were observed, thermoregulation was disrupted by letrozole in females only, indicating some impact on hypothalamic activity. These findings suggest adverse effects of AIs on the primate brain and call for new therapies that effectively prevent breast cancer recurrence while minimizing side effects that further compromise quality of life.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adverse Effects of Aromatase Inhibition on the Brain and Behavior in a Nonhuman Primate

et al. 2018

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“…Consolidating recent experience in other contexts and systems require presynaptic signaling molecules ('neuromodulators'), such as brain-derived estrogens. The predominant estrogen 17β-estradiol (E2) is a candidate neuromodulator required for auditory memory consolidation, as is evident in a similar role in adult hippocampal-dependent cognition, across taxa (Vierk et al, 2012;Srivastava et al, 2013;Luine, 2014) (Woolley and McEwen, 1992;Packard and Teather, 1997;Packard, 1998;Woolley, 2007;Frick, 2012;Bailey et al, 2013;Rensel et al, 2013;Bailey and Saldanha, 2015;Rensel et al, 2015;Barth et al, 2016;Tuscher et al, 2016;Bailey et al, 2017;Blaustein, 2017;Bayer et al, 2018), but see (Korol and Pisani, 2015). Additionally, both circulating and brain-derived estrogens ('neuroestrogens') typically enhance hearing (Caras, 2013;Caras and Remage-Healey, 2016), and are associated with language and verbal memory in humans (Fernandez et al, 2003;Zimmerman et al, 2011;Anthoni et al, 2012;Wermke et al, 2014;Schaadt et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Blocking neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation accuracy in developing songbirds

Hecsh

Remage‐Healey

2019

Preprint

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Birdsong, like human speech, is learned early in life by first memorizing an auditory model. Once memorized, birds compare their own burgeoning vocalizations to their auditory memory, and adjust their song to match the model. While much is known about this latter part of vocal learning, less is known about how initial auditory experiences are formed and consolidated. In both adults and developing songbirds, there is strong evidence suggesting the caudomedial nidopallium (NCM), a higher order auditory forebrain area, is the site of auditory memory consolidation. However, the mechanisms that facilitate this consolidation are poorly understood. One likely mechanism is 17β-estradiol (E2), which is associated with speech-language development and disorders in humans, and is abundant in both mammalian temporal cortex and songbird NCM. Circulating E2 is also elevated during the auditory memory phase, and in NCM immediately after song learning sessions, suggesting it functions to encode recent auditory experience. Therefore, we tested a role for E2 production in auditory memory consolidation during development using a comprehensive set of investigations to ask this question at the level of neuroanatomy, neurophysiology, and behavior. Our results demonstrate that while systemic estrogen synthesis blockade regulates juvenile song production, inhibiting E2 synthesis locally within NCM does not adversely affect song learning outcomes. Surprisingly, early life E2 manipulations in NCM modify the neural representations of birds' own song and the model tutor song in both NCM and a downstream sensorimotor nucleus (HVC). Further, we show that the capacity to synthesize neuroestrogens remains high throughout development alongside substantial changes in NCM cell density across age. Taken together, these findings suggest that E2 plays a multifaceted role during development, and demonstrate that contrary to prediction, unilateral post-training estrogen synthesis blockade in the auditory cortex does not negatively impact vocal learning. Acute downregulation of neuroestrogens are therefore likely permissive for juvenile auditory memorization, while neuroestrogen synthesis influences communication production and representation in adulthood. AntibodiesAntibodies and dilutions for aromatase and parvalbumin were identical to those used in Ikeda et al. (2017). Briefly, we used a polyclonal anti-aromatase primary antibody raised in rabbit (1:2,000; a generous gift from Dr. Colin Saldanha), and a monoclonal anti-parvalbumin primary antibody raised in mouse (1:10,000; Millipore MAB1572; RRID: AB_2174013). Secondary antibodies included goat antirabbit Alexa 488 (1:500; Thermo Fisher Scientific Inc.), and goat anti-mouse Alexa 647 (1:100; Thermo Fisher Scientific Inc.). ProcedureBrain sections were first manually washed 3 x in 0.1 M PB, followed by 3 x 15-minute washes in 0.1 M PB on a plate shaker, followed by a 2-hour incubation at room temperature with 10% normal goat serum (Vector) in 0.3 % PBT. Tissue was then transferred to a 10% normal goat...

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Cognitive sequelae of endocrine therapy in women treated for breast cancer: a meta-analysis

Underwood

Rochon

Moineddin

et al. 2017

Breast Cancer Res Treat

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Treatments for Breast Cancer That Affect Cognitive Function in Postmenopausal Women

Cited by 11 publications

References 80 publications

Adverse Effects of Aromatase Inhibition on the Brain and Behavior in a Nonhuman Primate

Adverse Effects of Aromatase Inhibition on the Brain and Behavior in a Nonhuman Primate

Blocking neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation accuracy in developing songbirds

Cognitive sequelae of endocrine therapy in women treated for breast cancer: a meta-analysis

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