Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin

Ross, Ronald K.; Paganini‐Hill, Annlia; Wan, Peggy; Pike, Malcolm C.

doi:10.1093/jnci/92.4.328

Cited by 791 publications

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“…Early menarche and late menopause increase breast cancer risk, as they prolong exposure to oestrogen and progesterone. [13][14][15][16][17][18][19][20][21][22] Long-term combined hormone replacement therapy (HRT) treatment (> 5 years) after the menopause is associated with a significant increase in risk. However, shorter-term treatments may still be associated with risk to those with a family history of breast cancer.…”

Section: Hormonal and Reproductive Risk Factorsmentioning

confidence: 99%

“…15 Oestrogen-only HRT has a risk that appears much lower, and it may be risk neutral. [16][17][18][19] A meta-analysis also suggested that both during current use of the combined oral contraceptive and 10 years post use, there may be a 24% increase in risk of breast cancer. 13 A woman's age at first pregnancy influences the relative risk (RR) of breast cancer, as pregnancy transforms breast parenchymal cells into a more stable state, potentially resulting in less proliferation in the second half of the menstrual cycle.…”

Section: Hormonal and Reproductive Risk Factorsmentioning

confidence: 99%

“…It is becoming clear that the risk from combined oestrogen/ progesterone HRT is greater than that from oestrogen only. 16,17,19 Interestingly, the increase in risk is lower in overweight women, but these women are likely to already be at increased risk from endogenous hormone production, with a RR of 2 for women who have gained ≥ 20 kg since the age of 18 years. 31,32 It is important to emphasise that these factors do not have an all-or-nothing effect on the breast, but may alter risks by a factor of 2 at the extremes.…”

Section: Other Risk Factorsmentioning

confidence: 99%

“…[16][17][18][19] The results of a meta-analysis suggest that HRT appears to increase risk cumulatively by 1-2% per year, although the risk disappears within 5 years of cessation. 15 A meta-analysis suggested that both during current use of the combined oral contraceptive and 10 years post use, there may be a 24% increase in risk of breast cancer.…”

Section: -21mentioning

confidence: 99%

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Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study

Evans

Astley

Stavrinos³

et al. 2016

Programme Grants Appl Res

117

126

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BackgroundIn the UK, women are invited for 3-yearly mammography screening, through the NHS Breast Screening Programme (NHSBSP), from the ages of 47–50 years to the ages of 69–73 years. Women with family histories of breast cancer can, from the age of 40 years, obtain enhanced surveillance and, in exceptionally high-risk cases, magnetic resonance imaging. However, no NHSBSP risk assessment is undertaken. Risk prediction models are able to categorise women by risk using known risk factors, although accurate individual risk prediction remains elusive. The identification of mammographic breast density (MD) and common genetic risk variants [single nucleotide polymorphisms (SNPs)] has presaged the improved precision of risk models.ObjectivesTo (1) identify the best performing model to assess breast cancer risk in family history clinic (FHC) and population settings; (2) use information from MD/SNPs to improve risk prediction; (3) assess the acceptability and feasibility of offering risk assessment in the NHSBSP; and (4) identify the incremental costs and benefits of risk stratified screening in a preliminary cost-effectiveness analysis.DesignTwo cohort studies assessing breast cancer incidence.SettingHigh-risk FHC and the NHSBSP Greater Manchester, UK.ParticipantsA total of 10,000 women aged 20–79 years [Family History Risk Study (FH-Risk); UK Clinical Research Network identification number (UKCRN-ID) 8611] and 53,000 women from the NHSBSP [aged 46–73 years; Predicting the Risk of Cancer At Screening (PROCAS) study; UKCRN-ID 8080].InterventionsQuestionnaires collected standard risk information, and mammograms were assessed for breast density by a number of techniques. All FH-Risk and 10,000 PROCAS participants participated in deoxyribonucleic acid (DNA) studies. The risk prediction models Manual method, Tyrer–Cuzick (TC), BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) and Gail were used to assess risk, with modelling based on MD and SNPs. A preliminary model-based cost-effectiveness analysis of risk stratified screening was conducted.Main outcome measuresBreast cancer incidence.Data sourcesThe NHSBSP; cancer registration.ResultsA total of 446 women developed incident breast cancers in FH-Risk in 97,958 years of follow-up. All risk models accurately stratified women into risk categories. TC had better risk precision than Gail, and BOADICEA accurately predicted risk in the 6268 single probands. The Manual model was also accurate in the whole cohort. In PROCAS, TC had better risk precision than Gail [area under the curve (AUC) 0.58 vs. 0.54], identifying 547 prospective breast cancers. The addition of SNPs in the FH-Risk case–control study improved risk precision but was not useful inBRCA1(breast cancer 1 gene) families. Risk modelling of SNPs in PROCAS showed an incremental improvement from using SNP18 used in PROCAS to SNP67. MD measured by visual assessment score provided better risk stratification than automatic measures, despite wide intra- and inter-reader variability. Using a MD-adjusted TC model in PROCAS improved risk stratification (AUC = 0.6) and identified significantly higher rates (4.7 per 10,000 vs. 1.3 per 10,000;p < 0.001) of high-stage cancers in women with above-average breast cancer risks. It is not possible to provide estimates of the incremental costs and benefits of risk stratified screening because of lack of data inputs for key parameters in the model-based cost-effectiveness analysis.ConclusionsRisk precision can be improved by using DNA and MD, and can potentially be used to stratify NHSBSP screening. It may also identify those at greater risk of high-stage cancers for enhanced screening. The cost-effectiveness of risk stratified screening is currently associated with extensive uncertainty. Additional research is needed to identify data needed for key inputs into model-based cost-effectiveness analyses to identify the impact on health-care resource use and patient benefits.Future workA pilot of real-time NHSBSP risk prediction to identify women for chemoprevention and enhanced screening is required.FundingThe National Institute for Health Research Programme Grants for Applied Research programme. The DNA saliva collection for SNP analysis for PROCAS was funded by the Genesis Breast Cancer Prevention Appeal.

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Section: Hormonal and Reproductive Risk Factorsmentioning

confidence: 99%

Section: Hormonal and Reproductive Risk Factorsmentioning

confidence: 99%

Section: Other Risk Factorsmentioning

confidence: 99%

Section: -21mentioning

confidence: 99%

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Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study

Evans

Astley

Stavrinos³

et al. 2016

Programme Grants Appl Res

117

126

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“…About 65% of estrogen positive breast cancers are also progesterone receptors positive, which means that progesterone may turn on breast cancer cell growth [14]. However, progesterone proliferative effects on mammary gland development and tumor genesis are not well recognized [15][16][17].…”

mentioning

confidence: 99%

Relationship between plasma progesterone, estradiol and prolactin concentrations and breast cancer in pre and postmenopausal women

Sn¹,

Atoum²,

Al-Hourani³

et al. 2010

neo

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74Breast cancer is the second most common cancer among women after skin cancer and is the second most common cause of death among women after lung cancer. The causes of breast cancer are very complicated. Although about 7% of breast cancers are of genetical background, the rest are due to environmental causes [1]. Hormones such as estrogen, progesterone and prolactin are implicated in a number of ways as possible causes of breast cancer. Throughout women life cycle, breast development and function depend on complex critical interplay of these hormones [2]. Many breast cancers are hormone dependent, meaning hormones turn on breast cancer cell growth.Estradiol is considered the most significant breast cancer risk factor because of its direct role in stimulation breast cell division or via its effects on other hormones and due its support of the growth of estrogen-responsive tumors [2]. Although, no study has clearly demonstrated a relationship between breast cancer and estrogen levels in premenopausal women [3]. Women with high estrogen levels were more likely to go on to develop breast cancer [4]. Postmenopausal women with high plasma estrogen levels have twice the risk of developing breast cancer as women with low levels [5].Prolactin hormone is essential for breast development and lactation [6][7][8]. High plasma prolactin levels were associated with a modestly increased risk of postmenopausal breast cancer [7,8]. About 95% of breast cancers expressed receptors for prolactin, meaning that they would be responsive to the stimulatory effect of prolactin [9][10][11]. However, in a study by Tworoger et al [12], a non significant positive relationship between prolactin levels and postmenopausal breast cancer was observed. Progesterone stimulates breast development during pregnancy [13]. About 65% of estrogen positive breast Received March 31, 2009Hormones such as estrogen, progesterone and prolactin are implicated in a number of ways as possible causes of breast cancer. Throughout women life cycle, breast development and function depend on complex critical interplay of these hormones. The acknowledged gaps in our understanding concerning progesterone, estrogen and prolactin hormones involvement in human breast cancer has exposed the need to conduct this study for better understanding of the role played by these hormones in breast cancer during pre and post menopause status in order to influence prevention and treatment of breast cancer. Ninety women were enrolled, (80%) of them were breast cancer patients and the other (20%) were breast benign lesion patients. At attending King Hussein Medical Center, blood samples were collected and analyzed for plasma estradiol, prolactin and progesterone. Of the 72 breast cancer patients (66.6% and 33.4%), and of the 18 breast benign patients (27.8% and 72.2%) were in menopause and premenopausal, respectively. Of the breast cancer and benign patients groups, 55.6% of each had an association with either high plasma estradiol, prolactin or progesterone concentrations. Of the brea...

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Hormone Replacement Therapy in Relation to Breast Cancer

Chen¹

2002

JAMA

316

167

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Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin

Abstract: This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have important implications for the risk-benefit equation for HRT in women using CHRT.

Cited by 791 publications

References 0 publications

Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study

Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study

Relationship between plasma progesterone, estradiol and prolactin concentrations and breast cancer in pre and postmenopausal women

Hormone Replacement Therapy in Relation to Breast Cancer

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