Breast Cancer in DES Daughters

The incidence of breast cancer associated with DES may increase with additional follow-up time

1993 Review Abstract

It is estimated that 2 million US women used diethylstilbestrol (DES), a nonsteroidal estrogen, to reduce the risk of fetal loss from the late 1940s through the early 1960s. The results of clinical trials of the effectiveness of DES in the early 1950s precipitated the eventual decline of DES prescription by the 1960s.

Concern about the breast cancer risk associated with the high dose of stilbestrol used led to 2 follow-up studies of these clinical trial participants, as well as 2 other retrospective cohort studies to examine the subsequent risk of breast cancer in DES-exposed women.

3 of the 4 studies reported positive results, with an overall 50% increase in risk for ever using DES during pregnancy and an apparent latency period of more than 20 years.

These studies have or more limitations, including the absence of information on dosage taken and duration of use, confusion about the identify of the exposed group and the inability to distinguish between the effect of DES and the effect of indications for using DES. Nevertheless, the findings supported a possible association between DES and breast cancer risk.

The 4 studies were published between 1980 and 1984 and included many women who had only recently entered the age period when breast cancer incidence is high. It is possible that the incidence of breast cancer associated with DES may increase with additional follow-up time.

Prenatal influences on carcinogenesis have recently become of interest in the etiology of adult cancer, and, in particular, it has been proposed that increased estrogen levels during pregnancy might increase the probability of breast cancer in daughters. It has been demonstrated that DES use during pregnancy can influence the subsequent risk of clear cell adenocarcinoma in offspring, although the issue of whether DES might also influence the subsequent risk of breast cancer in daughters remains to be investigated.

Sources

  • Diethylstilbestrol (DES) and breast cancer, Epidemiologic reviews, NCBI PubMed PMID: 8405194, 1993.
DES DIETHYLSTILBESTROL RESOURCES

Does breast cancer originate in utero?

Higher risk of breast cancer in women prenatally exposed to diethylstilbestrol

1990 Study Abstract

Factors that increase the risk of cancer during adult life may also increase the risk of cancer when they act in utero (eg, ionising radiation and diethylstilboestrol in human beings and chemicals in animals).

The existing empirical data seem to be compatible with the hypothesis that increased concentrations of oestrogens in pregnancy increase the probability of future occurrence of breast cancer in daughters.

Sources

  • Hypothesis: does breast cancer originate in utero?, The Lancet, NCBI PubMed PMID: 1970028, 1990 Apr.
  • Featured image pexels.
DES DIETHYLSTILBESTROL RESOURCES

DES Exposure Mechanism leading to Breast Cancer

Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo

2014 Study Abstract

Antisense transcript, long non-coding RNA HOTAIR is a key player in gene silencing and breast cancer and is transcriptionally regulated by estradiol. Here, we have investigated if HOTAIR expression is misregulated by bisphenol-A (BPA) and diethylstilbestrol (DES). Our findings demonstrate BPA and DES induce HOTAIR expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of rat. Luciferase assay showed that HOTAIR promoter estrogen-response-elements (EREs) are induced by BPA and DES. Estrogen-receptors (ERs) and ER-coregulators such as MLL-histone methylases (MLL1 and MLL3) bind to the HOTAIR promoter EREs in the presence of BPA and DES, modify chromatin (histone methylation and acetylation) and lead to gene activation. Knockdown of ERs down-regulated the BPA and DES induced expression of HOTAIR. In summary, our results demonstrate that BPA and DES exposure alters the epigenetic programming of the HOTAIR promoters leading to its endocrine disruption in vitro and in vivo.

It is important to note that, HOTAIR is an antisense transcript and lncRNA. Therefore, our studies also demonstrate that endocrine disruptors can disrupt the noncoding RNAs and can induce antisense transcripts, in a similar fashion as protein coding genes from the sense strands. Our studies revealed novel epigenetic mechanism of endocrine disruption, novel roles of MLL histone methylases and their coordination with ERs and various ER-coregulators during endocrine disruption, both in vitro and in vivo. Although further in vivo analyses are required to understand the detailed mechanism of HOTAIR gene expression and misregulation by EDCs, synthetics estrogens, and other environmental toxins/chemical, our observations indicate that exposure to BPA or DES may turn on the expression of HOTAIR in vivo, in a very similar fashion to estrogen even in the absence of estrogen, and that may result in adverse health effects including cancer and other hormonally regulated disorders.

Sources

  • Full study (free access) : Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo, The Journal of steroid biochemistry and molecular biology, NCBI PubMed PMC4025971, 2014.
  • Featured image : Models showing the roles of ERs, MLLs and other ER-coregulators during BPA and DES mediated endocrine disruption of HOTAIR. PMC4025971/figure/F7.
DES DIETHYLSTILBESTROL RESOURCES

Increased Breast Cancer risk in DES-Exposed Progeny

Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters, 2014

Study Summary

The idea that susceptibility to breast cancer is determined not only through inherited germline mutations but also by epigenetic changes induced by alterations in hormonal environment during fetal development is gaining increasing support. Using findings obtained in human and animal studies, this review addresses the mechanisms that may explain why daughters of mothers who took synthetic estrogen diethylstilbestrol (DES) during pregnancy have two times higher breast cancer risk than women who were not exposed to it. The mechanisms likely involve epigenetic alterations, such as increased DNA methylation and modifications in histones and microRNA expression.Further, these alterations may target genes that regulate stem cells and prevent differentiation of their daughter cells. Recent findings in a preclinical model suggest that not only are women exposed to DES in utero at an increased risk of developing breast cancer, but this risk may extend to their daughters and granddaughters as well. It is critical, therefore, to determine if the increased risk is driven by epigenetic alterations in genes that increase susceptibility to breast cancer and if these alterations are reversible.

Abstracts

In this review, findings related to in utero DES exposure and breast cancer are discussed for the purpose of weighing evidence as to whether fetal hormonal environment can impact breast cancer risk in women several decades later. Since causal studies can readily be performed using animal models, findings obtained in DES-exposed mouse and rat offspring also are discussed. Importantly, animal studies were done prior to any epidemiological studies addressing a possible link between maternal DES exposure and breast cancer risk among daughters could be performed. By the 1980s, exposed daughters in the cohorts began to be old enough to develop breast cancer and several human studies have been performed since to determine if maternal exposure to DES during pregnancy increases an offspring’s breast cancer risk.

…”The animal studies show that the doses of DES relevant to pregnant women increased later risk of developing mammary tumors. Specifically, female offspring of rat dams exposed to a total of 1.2 μg DES either on gestation week 2 or 3, to 0.6 μg or 4 μg DES on both gestation days 15 and 18 (all via injection), or via diet to 0.1, 1 or 10 ppm DES between gestation days 13 and 21 (week 3) exhibited increased mammary cancer risk. An increase in risk also was seen in rats exposed to a single dose of 0.1, 1 or 10 μg or less of DES at birth.” …

…”Importantly, in utero exposure to DES leads to an increase in terminal end buds (TEBs) numbers. It is thus possible that one of the mechanisms causing an increase in mammary cancer risk in DES offspring is an increase in the number of targets for malignant transformation.”…

…”Several published studies have investigated breast cancer risk in the daughters of DES mothers, the majority of which were cohort studies done in the US. As the women in the cohorts aged, their breast cancer risk grew higher, compared with matched non-exposed controls. The findings clearly indicate that after age 40 years the incidence of breast cancer is at least two-fold higher in the daughters of DES-exposed mothers. Many pregnant women in Europe and Australia also used DES, but the peak exposure occurred 10 to 20 years later than in the US, and this probably explains why a recent study done in Europe found a trend but not a significant increase in breast cancer risk among them. Once the European daughters reach the age when breast cancer is more commonly detected, they too are likely to exhibit a significant increase in breast cancer risk.”…

To summarize, animal and human studies have generated similar findings and indicate that there is a causal link between maternal exposure to DES during pregnancy and increased breast cancer risk among female offspring. According to animal studies, the increase in risk may reflect the presence of a higher number of TEBs in the mammary epithelium in the DES offspring. Baik and colleagues have proposed that the increase in mammary epithelial cells in in utero estrogen-exposed females is caused by a high number of mammary stem cells or an increase in their potential to generate daughter cells. Our unpublished data support this conclusion”

Epigenetic alterations induced by in utero diethylstilbestrol exposure

We and others have observed that the expression of DNA methyltransferases (DNMTs) is persistently altered in estrogen-regulated tissues following estrogenic exposures during early life. In utero exposure to DES is reported to increase the expression of DNMT1 in the epididymis and uterus. We found that DNMT1 expression is increased in the mammary glands of adult rat offspring of dams exposed to ethinyl estradiol during pregnancy. These changes provide a key regulatory layer to influence gene expression in the mammary gland and perhaps breast tumors of individuals exposed to DES or other estrogenic compounds in utero.

The effects of maternal diethylstilbestrol exposure are not limited to the F1 generation?

Some researchers have begun to investigate whether the effects of maternal DES exposure during pregnancy extend to the third generation in humans. Although there is no evidence that DES granddaughters have cervical and ovarian abnormalities similar to DES daughters, there is evidence that they may have more menstrual irregularities and a higher rate of infertility than non-exposed granddaughters. In addition, DES granddaughters may have a slightly higher risk of ovarian cancer. The granddaughters are still too young to assess whether they might also be at an increased risk of developing breast cancer.

Millions of women in the US, Europe and Australia have been exposed to DES in the womb, and consequently exhibit about a two times higher breast cancer risk than unexposed women. The increase in risk may not be limited to the DES-exposed daughters, but could also increase breast cancer risk in granddaughters and great granddaughters. Such outcome would be consistent with the findings we obtained in studies using a synthetic estrogen ethinyl estradiol (EE2). If DES has similar effects to ethinyl estradiol on the transgenerational increase in breast cancer risk, it is urgent to find ways to stop the cycle of inheritance, and also prevent breast cancer in DES-exposed granddaughters and great granddaughters.

To achieve this goal, we need to understand how maternal DES exposure during pregnancy increases a daughter’s breast cancer risk. A plausible model is proposed in the featured image. It is evident from studies done in animal models that in utero DES exposure induces epigenetic changes in reproductive tract tissues and the breast. DES exposure might also have induced epigenetic changes in primordial germ cells and consequently germ cells, and further be detectable in the somatic cells in granddaughters and great granddaughters. We are not aware of any study that has compared epigenetic changes in germ cells and the next generation somatic cells in individuals exposed to DES or other endocrine disruptors in utero. Second, we should investigate whether the transgenerational increase in breast cancer risk can be prevented with drugs that reverse epigenetic modifications. Our preliminary studies in mice suggest that this is achievable in daughters by using the well-tolerated and non-toxic histone deacetylase inhibitor valproic acid and DNMT inhibitor hydralazine. However, whether these compounds also prevent an increase in granddaughters and great granddaughters in experimental models remains to be investigated.

Sources

  • Full study (free access) : Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters, Breast cancer research : BCR, NCBI PubMed PMC4053091, 2014.
  • Featured image : Proposed model to explain an increase in breast cancer risk in daughters, and possibly granddaughters and great granddaughters, of mothers who took diethylstilbestrol during pregnancy. DES, diethylstilbestrol; TDLU, terminal ductal lobular unit; TEB, terminal end bud. PMC4053091/figure/F1.
DES DIETHYLSTILBESTROL RESOURCES

DES Daughters’ Cancer Risk

Cancer risk in women prenatally exposed to diethylstilbestrol, 2007

Study Abstract

Prenatal diethylstilbestrol (DES) exposure is associated with excess risks of clear cell adenocarcinoma (CCA), and breast cancer in older women. Whether overall cancer risk is also elevated is unclear.

Total and site-specific cancer risks were evaluated in the DES Combined Cohort Follow-up Study using age- and calendar-year specific standardized incidence rate ratios (SIR), and age-adjusted incidence rate ratios (RR) comparing DES exposed and unexposed women. A total of 143 and 49 cancer cases occurred in 97,831 and 34,810 person-years among the exposed and unexposed, respectively.

  • There was no overall excess risk among exposed women when compared with external rates (SIR 1.01; 95% confidence interval [CI] 0.86-1.2).
  • The overall RR comparing exposed with unexposed women was 1.32 (95% CI 0.94-1.8).
  • Breast cancer risk was elevated only among women over 40 years (RR 1.83; 95% CI 1.1-3.2).
  • The CCA SIR among exposed women was nearly 40, and the estimated attack rate through age 39 was 1.6/1,000 women. CCA incidence decreased by over 80% after age 25 when compared with 20-24 years.
  • Excluding CCA and breast cancer, the overall RR was 1.21 (95% CI 0.74-2.0).
  • DES was not associated with excess risks of either endometrial or ovarian cancer.

These data suggest that the DES associated increase in CCA incidence remains elevated through the reproductive years. There was no consistent evidence of risk excesses for cancers other than CCA, and breast cancer in older women.

Given that the population is still young, continued follow-up is necessary to assess the overall carcinogenic impact of prenatal DES exposure.

Sources

  • Cancer risk in women prenatally exposed to diethylstilbestrol, International journal of cancer, NCBI PubMed PMID: 17390375, 2007 Jul 15.
DES DIETHYLSTILBESTROL RESOURCES

DES mammary carcinomas linked to neonatal periods of exposure and doses

Effects of neonatally administered low-dose diethylstilbestrol on the induction of mammary carcinomas and dysplasias induced by 7,12-dimethylbenz [a] anthracene in female rats

2008 Study Abstract

The aim of this study was to investigate the effects of neonatal administration of diethylstilbestrol (DES) on the induction of mammary carcinomas (MCs) and dysplasias (MDs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats.

Three different methods of continuous administration of DES (1 microg) were used: 0-14, 0-5 and 6-14 days after birth, and all rats were given DMBA (10 mg) at 50 days after birth.

  • All rats administered DES showed persistent estrus and anovulatory ovaries.
  • In rats administered DES from 0-14 days after birth, neither MCs nor MDs were observed, and serum levels of both estrogen and progesterone were significantly lower than in controls at 100 days after birth.
  • In rats administered DES from 0-5 days after birth, the incidence and number of MCs were significantly lower while the number ofMDs was slightly higher than in controls.
  • In rats administered DES from 6-14 days after birth, the incidence of MCs was equal to that of the controls while the incidence and number ofMDs were significantly higher.

These results suggest that neonatal periods of exposure and doses of endocrine disruptors, such as DES, could affect the incidence and progression of MCs and MDs.

Sources

  • Full study (free access) : Effects of neonatally administered low-dose diethylstilbestrol on the induction of mammary carcinomas and dysplasias induced by 7,12-dimethylbenz [a] anthracene in female rats, In Vivo, NCBI PubMed PMID: 18468405, 2008 Mar-Apr.
DES DIETHYLSTILBESTROL RESOURCES

DES doses relevant to pregnant women increased later risk of developing mammary tumors

Transplacental action of diethylstilbestrol on mammary carcinogenesis in female rats given one or two doses of 7,12-dimethylbenz(a)anthracene

1983 Study Abstract

Aspects of the development, morphology, and estrogen binding capacity of mammary tumors in rats exposed prenatally to the synthetic estrogen, diethylstilbestrol (DES), and treated postnatally with 7,12-dimethylbenz(a)anthracene (DMBA) were analyzed as part of a project aimed at understanding the effects of transplacental exposure to DES on estrogen-sensitive tissues.

Pregnant Sprague-Dawley rats were given injections of DES (total dose, 1.2 micrograms) or vehicle alone on Days 15 and 18 of gestation. All female offspring were given gastric intubations of DMBA, either a single 10-mg dose on Day 50 or two doses (10 mg each) on Days 50 and 57.

Among rats treated postnatally with 10 mg of DMBA, the DES-exposed group had a significantly greater incidence of palpable mammary tumors than did the vehicle-exposed controls. In addition, there was an earlier time of appearance of palpable tumors in the DES-exposed group.

When the data from rats treated postnatally with two 10-mg doses of DMBA were analyzed, there were no significant differences in palpable mammary tumor incidence or tumor latency between the DES-exposed and vehicle-exposed groups.

When the pathology of the mammary tumors produced in rats treated with 10 mg of DMBA was analyzed, the DES-exposed group had a significantly higher proportion of benign tumors (fibroadenoma, adenoma, lobular hyperplasia) than adenocarcinomata compared to vehicle-exposed controls. Both exposure groups had similar numbers of nonpalpable mammary lesions discovered at necropsy.

Estrogen binding capacities of representative adenocarcinomata did not differ significantly between the two prenatal exposure groups treated postnatally with 10 mg of DMBA.

These results demonstrate the importance of the dose of the challenge carcinogen in revealing the effects of transplacental drug exposure and may have special significance for women who were exposed to DES in utero.

Sources

  • Transplacental action of diethylstilbestrol on mammary carcinogenesis in female rats given one or two doses of 7,12-dimethylbenz(a)anthracene, Cancer research, NCBI PubMed PMID: 6411335, 1983 Oct.
DES DIETHYLSTILBESTROL RESOURCES

Breast cancer predisposition due to prenatal DES exposure

Does cancer start in the womb? Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors

2013 Study Summary

We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to diethylstilbestrol resulted in clear cell carcinoma of the vagina and breast cancer. In this review the effects of the endocrine disruptor bisphenol-A (BPA) on mammary development and tumorigenesis in rodents is used as a paradigmatic example of how altered prenatal mammary development may lead to breast cancer in humans who are also widely exposed to it through plastic goods, food and drink packaging, and thermal paper receipts. Changes in the stroma and its extracellular matrix led to altered ductal morphogenesis. Additionally, gestational and lactational exposure to BPA increased the sensitivity of rats and mice to mammotropic hormones during puberty and beyond, thus suggesting a plausible explanation for the increased incidence of breast cancer.

Abstracts

… Breast cancer risk at 40 years of age and older is 2.5 fold higher in DES-exposed women than in unexposed women of the same age. In rats, prenatal exposure to DES also resulted in increased mammary cancer incidence during adulthood when these animals were challenged with the chemical carcinogen dimethylbenzanthracene (DMBA) at puberty. DES was administered to rats at pharmacological doses to mimic its medical use. …

… The causal link between fetal exposure to estrogens and the development of breast cancer that was first suggested by epidemiologists has now been confirmed by the increased risk to develop breast cancer during adulthood of women exposed to DES during their fetal life. Fetal and neonatal exposures to EDCs cause persistent alterations in the mammary glands of rodents, including pre- and neoplastic lesions, long after the exposure ended. …

Sources

  • Full study (free access) : Does cancer start in the womb? Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors, Journal of Mammary Gland Biology and Neoplasia, NCBI PubMed PMC3933259, 2013 May 24.
  • Featured image PMC3933259/figure/F4.
DES DIETHYLSTILBESTROL RESOURCES

DES increases breast cancer risk in both exposed mothers and their daughters

Exposures to Synthetic Estrogens at Different Times During the Life, and Their Effect on Breast Cancer Risk

2013 Study Summary

Women are using estrogens for many purposes, such as to prevent pregnancy or miscarriage, or to treat menopausal symptoms. Estrogens also have been used to treat breast cancer which seems puzzling, since there is convincing evidence to support a link between high lifetime estrogen exposure and increased breast cancer risk.

In this review, we discuss the findings that maternal exposure to the synthetic estrogen diethylstilbestrol during pregnancy increases breast cancer risk in both exposed mothers and their daughters.

In addition, we review data regarding the use of estrogens in oral contraceptives and as postmenopausal hormone therapy and discuss the opposing effects on breast cancer risk based upon timing of exposure. We place particular emphasis on studies investigating how maternal estrogenic exposures during pregnancy increase breast cancer risk among daughters.

New data suggest that these exposures induce epigenetic modifications in the mammary gland and germ cells, thereby causing an inheritable increase in breast cancer risk for multiple generations.

Abstracts

Maternal Exposure to DES During Pregnancy and Breast Cancer Risk Among Daughters

… Several studies have been published that investigate breast cancer risk in the daughters of DES mothers, the majority of which are cohort studies done in the US. The same cohort of daughters has been followed in many of these studies, and as the women in the cohort grew older, their breast cancer risk grew higher, compared with matched non-exposed controls [67, 70, 71, 73, 74]. These studies clearly indicate that when both groups of women are old enough to develop breast cancer, the incidence is at least 2-fold higher in the daughters of DES-exposed mothers.

Many pregnant women in Europe and Australia also used DES, but the peak exposure occurred later than in the USA. Fig. 2 shows that the peak exposure in the USA was in the early 50’s, while in France it was in the late 1960’s and early 70’s. The fact that the daughters of DES-exposed mothers in Europe are younger than the daughters in the USA probably explains why a recent study done in Europe found a trend but not a significant increase in breast cancer risk among them [75]. Once the European daughters reach the age when breast cancer is more commonly detected, they too are likely to exhibit increased breast cancer risk. In summary, the findings in humans provide strong evidence that maternal DES exposure during pregnancy increases their daughters’ breast cancer risk. …

Findings in Animal Studies

Many animal studies have investigated the effect of in utero DES exposure on later mammary tumorigenesis [76–81]. The amount of DES given to pregnant mice or rat dams varied from study to study (0.2–12,000 µg/day, which translates in rats to approximately 1 µg/kg – 60 mg/kg DES per day; in pregnant women the DES dose ranged from 100 µg/kg to 2 mg/kg), as did the route of administration (subcutaneous injection or via feed) and mammary tumor model used (spontaneous, carcinogen-induced, or ACI rats which develop mammary tumors upon estrogen exposure). The animal studies show that the doses of DES relevant to pregnant women increased later risk of developing mammary tumors. The increase did not occur with the highest doses and exposures which started early in pregnancy [81, 82], probably because they prevented implantation or caused miscarriage in most of the exposed dams.

Conclusion

Women use estrogens for many purposes. During pregnancy, synthetic estrogen DES was used to prevent miscarriage and promote healthy pregnancy, although it turned out to cause the opposite. During the reproductive years when a woman’s own estrogen levels are high, women use synthetic estrogens as contraceptives. Since estrogens play an important role in normal physiological functions in women, some menopausal and postmenopausal women use estrogen supplementation to regain the benefits of natural estrogens.

The effects of estrogens on breast cancer risk differ depending upon when during a woman’s life time they are used. Maternal exposure to DES during pregnancy increases breast cancer risk in mothers and their daughters. The adverse effects of synthetic estrogen exposure during pregnancy may not be limited to mothers and their daughters. Our preclinical study in rodents showed that maternal exposure to EE2 increases breast cancer risk in daughters, granddaughters, and great granddaughters. The first generation of OCs increased breast cancer risk at the time women were taking them, but the increase in risk was not permanent. The current, third generation contraceptives do not increase breast cancer risk. Menopausal and postmenopausal HT, if it contains both estrogens and progestin, increases a woman’s breast cancer risk, and recent data suggest that tumors developing during therapy are more aggressive than those in women not using HT. Estrogen-only HT does not increase breast cancer risk, and might even reduce it. However, due to other adverse effects of estrogen-only HT, it is not recommended beyond using it to control the most severe menopausal symptoms.

We are beginning to understand how the increase in breast cancer risk following in utero exposures to synthetic estrogens occurs. It most likely involves long-term epigenetic changes in genes that are important in determining the risk for breast cancer development, such as tumor suppressor genes, PcTGs and oncogenes. The proposed sequence of events from the fetal estrogen exposure to an increase in breast cancer risk is illustrated in the featured image. Briefly, an exposure to synthetic estrogens during the fetal period induces modifications in the epigenetic reprogramming of the genome, leading to changes in mammary gland morphology, and gene and protein expression. Some of these changes are transient, such as an increase in the number of TEBs in rodents, and some persist, such as an altered gene and protein expression involving tumor suppressor genes and oncogenes. Together, epigenetically induced modifications in the mammary gland morphology and gene expression increase the likelihood that environmental carcinogens and radiation induce malignant transformation, and evetually breast cancer. The next challenge is to determine whether the increase in risk can be reversed by reversing epigenetic changes that occur as a consequence of early life exposure to synthetic estrogens.

Sources

  • Full study (free access) : Exposures to Synthetic Estrogens at Different Times During the Life, and Their Effect on Breast Cancer Risk, Journal of Mammary Gland Biology and Neoplasia, NCBI PubMed PMC3635108, 08 February 2013.
  • Featured image Proposed sequence of events from maternal exposure to estrogens during pregnancy to an increase in daughter’s breast cancer risk PMC3635108/figure/F3.
DES DIETHYLSTILBESTROL RESOURCES

DES stimulatory effect on the initiation of mammary carcinomas

Effects of neonatally administered diethylstilbestrol on induction of mammary carcinomas induced by 7, 12-dimethylbenz(a)anthracene in female rats

2007 Study Abstract

Various doses of diethylstilbestrol (DES) were administered to rats once at birth. Thereafter, at 50 days after birth, the rats in all groups were given 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA) and undergone necropsy at 300 days after birth.

The incidence of mammary carcinomas (MCs) were 50, 54, 91, 39, 19% at 175 days after birth, and 77, 87, 100, 85, 75% at necropsy in the 0, 0.1, 1, 10, 100 microg groups, respectively. The incidence of rats without corpus luteum were 0, 0, 0, 30, 100% at 50 days after birth, and 0, 40, 53, 93, 100% at necropsy in the 0, 0.1, 1, 10, 100 microg groups, respectively.

Observation of the whole mount specimens showed a higher number of terminal end buds (TEBs) in the 1 microg group and a lower number in the 100 microg group compared with the control at 50 days after birth.

It suggested that the administration of a relatively low dose (1 microg) of DES during neonatal period may increase TEBs, thus resulting in a stimulatory effect on the initiation of MCs.

Sources

  • Effects of neonatally administered diethylstilbestrol on induction of mammary carcinomas induced by 7, 12-dimethylbenz(a)anthracene in female rats, Teratogenesis, carcinogenesis, and mutagenesis, PMID: 17943655, 2007 Oct.
DES DIETHYLSTILBESTROL RESOURCES