Long-term hormonal promotion overcomes genetic resistance to mammary cancer

Lakshmanaswamy, Rajkumar; Arumugam, Arunkumar; Elsayed, Ahmed; Schecter, Scott; Kotkowski, Eithan; Castillo, Ruth; Torre, Aleyah de la; Hernandez, Cecilio M.

doi:10.1016/j.steroids.2010.08.004

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…Pregnancy also decreases the number of mammary stem cells [85, 86]. However, the protective pathways activated during pregnancy can be eroded by prolonged exposure to exogenous 17β-estradiol which restores sensitivity to carcinogen-induced mammary tumors [87–89]. These observations may explain why pregnancy is accompanied by a short-term increase in breast cancer risk [12, 90]; “pregnancy-associated breast cancer” has poorer overall survival [91, 92].…”

Section: Introductionmentioning

confidence: 99%

Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research

Michels²,

et al. 2019

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Background The long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman’s life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention. Main text Despite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland’s structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals—including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols—and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers. Conclusions An integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective.

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Section: Introductionmentioning

confidence: 99%

Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research

Michels²,

et al. 2019

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“…We have demonstrated that short-term treatment with estrogen or estrogen plus progesterone is effective in reducing breast cancer risk in rodent models [38][39][40]. We have also shown that long-term treatment with the same steroids increases the risk of breast cancer [41][42][43]. In conclusion, the evidence on duration of hormone treatment and the associated risk of breast cancer is controversial, with most of the data indicating that shorter treatment durations lead to decreased risk of breast cancer.…”

Section: Duration Of Hormone Therapy and Breast Cancer Riskmentioning

confidence: 85%

Dose, duration and mode of administration of hormones influence breast cancer risk

Lakshmanaswamy

2012

Drug Discovery Today: Disease Mechanisms

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“…It is also possible that systemic factors affect tumor development. Long-term hormone administration to COP rats has been reported to promote development of mammary tumors that would otherwise undergo spontaneous regression [44]. Fat tissue is a source of estrogen, especially after senescence of ovarian function; thus, obesity and being overweight promote breast cancer development [45].…”

Section: Plos Onementioning

confidence: 99%

Development of mammary cancer in γ-irradiated F1 hybrids of susceptible Sprague-Dawley and resistant Copenhagen rats, with copy-number losses that pinpoint potential tumor suppressors

et al. 2021

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Copenhagen rats are highly resistant to mammary carcinogenesis, even after treatment with chemical carcinogens and hormones; most studies indicate that this is a dominant genetic trait. To test whether this trait is also dominant after radiation exposure, we characterized the susceptibility of irradiated Copenhagen rats to mammary carcinogenesis, as well as its inheritance, and identified tumor-suppressor genes that, when inactivated or mutated, may contribute to carcinogenesis. To this end, mammary cancer–susceptible Sprague-Dawley rats, resistant Copenhagen rats, and their F1 hybrids were irradiated with 4 Gy of γ-rays, and tumor development was monitored. Copy-number variations and allelic imbalances of genomic DNA were studied using microarrays and PCR analysis of polymorphic markers. Gene expression was assessed by quantitative PCR in normal tissues and induced mammary cancers of F1 rats. Irradiated Copenhagen rats exhibited a very low incidence of mammary cancer. Unexpectedly, this resistance trait did not show dominant inheritance in F1 rats; rather, they exhibited intermediate susceptibility levels (i.e., between those of their parent strains). The susceptibility of irradiated F1 rats to the development of benign mammary tumors (i.e., fibroadenoma and adenoma) was also intermediate. Copy-number losses were frequently observed in chromosome regions 1q52–54 (24%), 2q12–15 (33%), and 3q31–42 (24%), as were focal (38%) and whole (29%) losses of chromosome 5. Some of these chromosomal regions exhibited allelic imbalances. Many cancer-related genes within these regions were downregulated in mammary tumors as compared with normal mammary tissue. Some of the chromosomal losses identified have not been reported previously in chemically induced models, implying a novel mechanism inherent to the irradiated model. Based on these findings, Sprague-Dawley × Copenhagen F1 rats offer a useful model for exploring genes responsible for radiation-induced mammary cancer, which apparently are mainly located in specific regions of chromosomes 1, 2, 3 and 5.

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Long-term hormonal promotion overcomes genetic resistance to mammary cancer

Cited by 9 publications

References 24 publications

Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research

Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research

Dose, duration and mode of administration of hormones influence breast cancer risk

Development of mammary cancer in γ-irradiated F1 hybrids of susceptible Sprague-Dawley and resistant Copenhagen rats, with copy-number losses that pinpoint potential tumor suppressors

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