Oral progestagens before menopause and breast cancer risk

Fabre, Alban; Fournier, Agnès; Mesrine, Sylvie; Desreux, Jean F.; Gompel, Anne; Boutron‐Ruault, Marie‐Christine; Clavel‐Chapelon, Françoise

doi:10.1038/sj.bjc.6603618

Cited by 32 publications

(24 citation statements)

References 27 publications

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“…According to the poorly understood etiology of all BBDs, current treatments are mostly empirical. One of the most currently used involves progestins, although the question of whether they are beneficial or instead deleterious for the breast is still a matter of debate (12). Some have tried antiestrogen therapy with tamoxifen in BBDs, but no evaluation of such practice has ever been reported.…”

mentioning

confidence: 99%

Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors

Bogorad

Courtillot

Mestayer

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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There is currently no known genetic disease linked to prolactin (Prl) or its receptor (PrlR) in humans. Given the essential role of this hormonal system in breast physiology, we reasoned that genetic anomalies of Prl/PrlR genes may be related to the occurrence of breast diseases with high proliferative potential. Multiple fibroadenomas (MFA) are benign breast tumors which appear most frequently in young women, including at puberty, when Prl has well-recognized proliferative actions on the breast. In a prospective study involving 74 MFA patients and 170 control subjects, we identified four patients harboring a heterozygous single nucleotide polymorphism in exon 6 of the PrlR gene, encoding Ile1463 Leu substitution in its extracellular domain. This sole substitution was sufficient to confer constitutive activity to the receptor variant (PrlRI146L), as assessed in three reconstituted cell models (Ba/F3, HEK293 and MCF-7 cells) by Prl-independent (i) PrlR tyrosine phosphorylation, (ii) activation of signal transducer and activator of transcription 5 (STAT5) signaling, (iii) transcriptional activity toward a Prl-responsive reporter gene, and (iv) cell proliferation and protection from cell death. Constitutive activity of PrlRI146L in the breast sample from a patient was supported by increased STAT5 signaling. This is a unique description of a functional mutation of the PrlR associated with a human disease. Hallmarks of constitutive activity were all reversed by a specific PrlR antagonist, which opens potential therapeutic approaches for MFA, or any other disease that could be associated with this mutation in future.antagonist ͉ breast diseases ͉ human mutation ͉ constitutive activity ͉ cytokine receptor

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mentioning

confidence: 99%

Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors

Bogorad

Courtillot

Mestayer

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Limitations described previously (8) include the absence of information on reasons for prescribing progestagens, their dose, and duration per cycle. Although the reasons for prescribing progestagens were not recorded, a potential ''prescription'' bias is unlikely because we adjusted for the variables ''personal history of benign breast disease'' and ''personal history of benign uterine or ovarian disease'', and because the effect of progestagens on breast cancer risk did not vary significantly according to a personal history of benign breast disease or to a personal history of benign uterine or ovarian disease.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that progestagens may increase breast cell proliferation as well as breast cancer cell proliferation (7), but the mechanisms by which progestagens operate in breast carcinogenesis remain largely unknown. In an earlier report, we showed a potential increase in breast cancer risk associated with the use of oral progestagens prescribed alone (i.e., without estrogen) before menopause (8), a treatment often prescribed in France for perimenopausal disorders, contraception, and gynecologic disorders such as breast pain, uterine, or ovarian pathologies and irregular menstruations (9).…”

Section: Introductionmentioning

confidence: 99%

Progestagens Use Before Menopause and Breast Cancer Risk According to Histology and Hormone Receptors

Fabre

Fournier

Mesrine

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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In a previous study, we found a positive association between premenopausal use of progestagens and breast cancer risk. We conducted the present study to assess the risk of breast cancers defined by their histology and hormone receptors status. We evaluated the association between progestagen-only intake (except for mini pills) before menopause and after the age of 40 years and invasive breast cancer risk in 67,057 women participating in the French E3N cohort study. Histologically confirmed invasive breast cancers (2,264) were identified through biennial self-administered questionnaires completed from 1992 to 2002. Risk estimates were calculated using the Cox proportional hazard model. We found an increased risk of lobular carcinoma associated with premenopausal use of progestagens among both current and past users [hazard raatio (HR), 1.51; 95% confidence interval (95% CI), 1.02-2.24 and HR, 1.38; 95% CI, 1.08-1.75, respectively]. Among current users, the use of progestagens for 4.5 years or more was associated with an increased risk of estrogen receptor -positive/progesterone receptor -positive carcinomas (HR, 1.68; 95% CI, 1.05-2.68), whereas current use of progestagens for <4.5 years was associated with an increase in the estrogen receptor -positive/progesterone receptornegative carcinoma risk (HR, 1.61; 95% CI, 1.05-2.46). The premenopausal use of progestagens after the age of 40 years may be preferentially associated with the risk of lobular breast cancer and differentially affect the risk of breast cancer according to the hormone receptor status. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2723 -8)

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“…Une réserve : l'augmentation du risque de cancer du sein après progestatifs pris avant la ménopause telle que l'a observé l'étude E3N [13]. Cependant, il faut prendre en compte que les femmes dans cette étude étaient en période préménopausique alors que les patientes atteintes d'endométriose sont généra-lement beaucoup plus jeunes.…”

Section: Les Progestatifs Purs Normodosésunclassified

Inhibition gonadotrope et endométriose. Comment lutter contre les dogmes s’ils sont erronés ?

Belaïsch¹

2009

Gynécologie Obstétrique & Fertilité

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Oral progestagens before menopause and breast cancer risk

Cited by 32 publications

References 27 publications

Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors

Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors

Progestagens Use Before Menopause and Breast Cancer Risk According to Histology and Hormone Receptors

Inhibition gonadotrope et endométriose. Comment lutter contre les dogmes s’ils sont erronés ?

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