Oral Contraceptives and the Risk of Breast Cancer

Marchbanks, Polly A.; McDonald, Jill A.; Wilson, Hoyt G.; Folger, Suzanne G.; Mandel, Michele G.; Daling, Janet R.; Bernstein, Leslie; Malone, Kathleen E.; Ursin, Giske; Strom, Brian L.; Norman, Sandra A.; Wingo, Phyllis A.; Burkman, Ronald T.; Berlin, Jesse A.; Simon, Michael S.; Spirtas, Robert; Weiss, Linda K.

doi:10.1056/nejmoa013202

Cited by 522 publications

(223 citation statements)

References 15 publications

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“…Multiple studies using different hormone formulations have reported contradictory effects of estrogen͞progestin use in breast cancer risk (9) and coronary heart disease (10). In light of our findings, discrepancies in outcomes could be, in part, attributable to differences in the cellular responses induced by different progestins.…”

Section: Discussionmentioning

confidence: 54%

“…Because progestins are added to HRT to prevent hyperplasia of the endometrium (7) and resulting uterine cancer (8), possible impacts of progestins need to be determined. Numerous studies have found contradictory effects of estrogen͞ progestin use and breast cancer (9), coronary heart disease (10), and cognition (11,12). Although some of these studies used the same hormone formulation [conjugated estrogens (Premarin) with medroxyprogesterone acetate (MPA; Provera)], many did not determine or subdivide the type of progestin used (9)(10)(11)(12)(13)(14), raising the possibility that the apparent discrepancies in outcomes are due to the differences in cellular responses induced by different progestins.…”

mentioning

confidence: 99%

“…Numerous studies have found contradictory effects of estrogen͞ progestin use and breast cancer (9), coronary heart disease (10), and cognition (11,12). Although some of these studies used the same hormone formulation [conjugated estrogens (Premarin) with medroxyprogesterone acetate (MPA; Provera)], many did not determine or subdivide the type of progestin used (9)(10)(11)(12)(13)(14), raising the possibility that the apparent discrepancies in outcomes are due to the differences in cellular responses induced by different progestins. Such concerns have been underscored by the termination of the combined regimen arm of the Women's Health Initiative trial (11,12,15).…”

mentioning

confidence: 99%

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Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling

Nilsen

Brinton

2003

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

228

157

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The impact of progestins on estrogen-inducible mechanisms of neuroprotection was investigated. Previously, we showed that estrogen and progesterone are neuroprotective against excitotoxicity, whereas the synthetic progestin medroxyprogesterone acetate (MPA; Provera) is not. Here, we demonstrate that 17␤-estradiol (E 2) and progesterone (P4) treatment of hippocampal neurons attenuated the excitotoxic glutamate-induced rise in intracellular calcium concentration. Although MPA had no effect alone, MPA completely antagonized E 2-induced attenuation of intracellular calcium concentration. Activation of extracellular receptor kinase (ERK) is required for estrogen-induced neuroprotection and calcium regulation. Paradoxically, E 2, P4, and MPA all elicited similar rapid and transient activation of ERK, presenting a contradiction between the dependence on ERK for gonadal hormone-induced neuroprotection and the lack of neuroprotection induced by MPA. Subcellular analysis of ERK demonstrated that the phospho-ERK signal is transduced to the nucleus only by E 2 and P4, not by MPA. These results indicate that the profile of nuclear translocation of ERK is consistent with the neuroprotective profile. Further, the E 2-induced nuclear translocation of ERK was blocked by coadministration of MPA. Results of this study reveal that nuclear ERK induction by ovarian steroids is predictive of the neuroprotective effects of estrogen and progestin treatments, revealing a hitherto unrecognized divergence of progestin signaling through the src͞ MAPK pathway. These results have much broader implications encompassing the impact of progestins on estrogen-mediated effects in multiple tissues. The recent results from the Women's Health Initiative trial, which used MPA as the progestinal agent, indicate that differences between progestin formulations are crucial to health outcomes in women.N eurologic benefits of estrogen replacement therapy in humans include reversal of estrogen deficiency-induced memory dysfunction and reduced risk of Alzheimer's disease (AD) (1-5). Recently, the Cache County Study confirmed a reduced risk of AD in elderly women on hormone replacement therapy (HRT) (6). Because progestins are added to HRT to prevent hyperplasia of the endometrium (7) and resulting uterine cancer (8), possible impacts of progestins need to be determined. Numerous studies have found contradictory effects of estrogen͞ progestin use and breast cancer (9), coronary heart disease (10), and cognition (11,12). Although some of these studies used the same hormone formulation [conjugated estrogens (Premarin) with medroxyprogesterone acetate (MPA; Provera)], many did not determine or subdivide the type of progestin used (9-14), raising the possibility that the apparent discrepancies in outcomes are due to the differences in cellular responses induced by different progestins. Such concerns have been underscored by the termination of the combined regimen arm of the Women's Health Initiative trial (11,12,15).In earlier work, we found that 17␤-estradiol (E 2...

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling

Nilsen

Brinton

2003

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

228

157

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“…Because of the original intention of studying lung injury in this cohort, data on some variables (e.g., age at menarche, hormone replacement therapy, and parity) was not obtained (50,51). These women received high-dose chemotherapy and BCT for high-risk disease and are therefore not representative of all women at risk for breast cancer (52).…”

Section: Discussionmentioning

confidence: 99%

Increased Prevalence of theHFE C282YHemochromatosis Allele in Women with Breast Cancer

Kallianpur

Hall

Yadav

et al. 2004

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Individuals with the major hemochromatosis (HFE) allele C282Y and iron overload develop hepatocellular and some extrahepatic malignancies at increased rates. No association has been previously reported between the C282Y allele and breast cancer. We hypothesized that due to the pro-oxidant properties of iron, altered iron metabolism in C282Y carriers may promote breast carcinogenesis. Because 1 in 10 Caucasians of Northern European ancestry carries this allele, any impact it may have on breast cancer burden is potentially great. We determined C282Y genotypes in 168 patients who underwent high-dose chemotherapy and blood cell transplantation for cancer: 41 with breast cancer and 127 with predominantly hematological cancers (transplant cohort). Demographic, clinical, and tumor characteristics were reviewed in breast cancer patients. The frequency of C282Y genotypes in breast cancers was compared with the frequency in nonbreast cancers, an outpatient sample from Tennessee (n ‫؍‬ 169), and a published United States national sample. The frequency of at least one C282Y allele in breast cancers was higher (36.6%, 5 homozygotes/10 heterozygotes) than frequencies in Tennessee (12.7%, P < 0.001), the general population (12.4%, P < 0.001), and similarly selected nonbreast cancers (17.0%, P ‫؍‬ 0.008). The likelihood of breast cancer in the transplant cohort increased with C282Y allele dose (P trend ‫؍‬ 0.010). These results were supported by the finding in a nontransplant cohort of a higher frequency of C282Y mutations in Caucasian (18.4%, P ‫؍‬ 0.039) and African-American (8.5%, P ‫؍‬ 0.005) women with breast cancer than race-specific national frequency estimates. A high prevalence of C282Y alleles in women with breast cancer with and without poor risk features suggests that altered iron metabolism in C282Y carriers may promote the development of breast cancer and/or more aggressive forms of the disease.

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“…Гормональний дисбаланс у тканинах МЗ в бік дефіциту прогестерону супроводжуєть-ся набряком і гіпертрофією сполучної тканини, а проліфе-рація епітелію протоків призводить до утворення кіст [7]. В генезі розвитку патології МЗ серед гормонів передньої долі гіпофізу особливе місце займає пролактин [23]. КЛАСИФІКАЦІЯ Є велика кількість класифікацій мастопатій.…”

Section: етіопатогенезunclassified

Fibrocystic mastopathy

Смоланка¹,

Ляшенко²

2014

Reproductive Endocrinology

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ВСТУПУпродовж останнього десятиріччя відмі-чається зростання числа доброякісних за-хворювань молочних залоз (МЗ), в тому числі дифузної фіброзно-кістозної мастопатії, яка діагностується, за даними різних авторів, у 60-80% жінок репродуктивного віку [1, 2].МЗ починають інтенсивно розвиватися у віці 12-16 років, коли посилюється функціо-нальна активність кори наднирників і стате-вих залоз. Будучи органом репродуктивної системи, МЗ відчувають безперервний гор-мональний вплив протягом всього життя жінки. Ріст і розвиток МЗ -складний про-цес, який не може відбуватися автономно. Існують складні нейрогуморальні механізми регуляції і висока чутливість тканин МЗ до статевих стероїдів і гіпофізарних пептидів, гормонів і біологічно активних речовин органів інших систем (наднирників, щито-видної залози, печінки) [2, 5, 6,15, 17]. Функ-ціонування МЗ тісно пов'язане з менстру-альною функцією [13].Тканини МЗ піддаються наступному гормо-нальному впливу [5,13]: естрогени викликають проліферацію про-токів і сполучної тканини МЗ; прогестерон -залозисту трансформацію альвеол; пролактин сприяє розвитку лактоцитів, секреції молока, є основним гормоном, який забезпечує лактацію; гормони щитовидної залози відіграють важливу роль у морфогенезі і функціональній диференціації епітеліальних клітин МЗ; інсулін діє на клітини МЗ опосередковано, через інші гормональні впливи; кортизон сприяє утворенню рецепторів пролактину в МЗ і стимулює ріст епітеліальних клітин у синергізмі з пролактином.

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Oral Contraceptives and the Risk of Breast Cancer

Abstract: Among women from 35 to 64 years of age, current or former oral-contraceptive use was not associated with a significantly increased risk of breast cancer.

Cited by 522 publications

References 15 publications

Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling

Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling

Increased Prevalence of theHFE C282YHemochromatosis Allele in Women with Breast Cancer

Fibrocystic mastopathy

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