Interaction between menopausal status and obesity in affecting breast cancer risk

Obesity has a complex relationship to breast cancer risk that differs in premenopausal and postmenopausal women. Before the menopause, the level of adiposity is inversely related to risk, indicative of a protective effect, whereas in postmenopausal women, particularly the elderly, the association is a positive one, consistent with obesity being a risk factor. The importance of high estrogen production in adipose tissue, with consequent elevation of circulating biologically available estradiol, in the promotional effect of obesity on postmenopausal breast carcinogenesis is well established; the resulting tumors express both estrogen and progesterone receptors. The mechanism(s) for the protective effect in premenopausal women is less well understood, but the breast cancers that do develop in the presence of obesity are most often estrogen and progesterone receptor negative, consistent with the selection of non-estrogen-dependent tumor cells which are dependent on growth factors such as insulin, insulin-like growth factor-I and some adipokines. The influence of menopausal status on the relationships between adiposity and breast cancer appears to be modified within each category by age; the protective effect before the menopause may be limited to younger women (<35 years), and the adverse effect was found to apply specifically to older postmenopausal women. Although randomized trials of weight reduction for postmenopausal breast cancer prevention have not been performed, observational studies suggested that risk reduction does occur; in addition, other health benefits of weight control need to be considered regardless of menopausal status.     

Physical activity and biomarkers in breast cancer survivors: A systematic review

Breast cancer is the most common cancer among women. The number of breast cancer survivors has increased due to screening and improved treatment methods, which makes it important to increase knowledge on their health and well-being. Physical activity has been reported to improve quality of life, decrease fatigue and reduce all-cause and breast cancer-specific mortality in breast cancer survivors. The beneficial effects of physical activity may manifest themselves in circulating levels of insulin, insulin-growth factors (IGFs) I and II and their binding proteins (IGFBPs), or inflammatory biomarkers. The aim of this report was to review available randomized controlled trials (RCTs) on the effects of physical activity on biomarkers in breast cancer survivors. We identified 12 publications based on nine RCTs that fulfilled our inclusion criteria published until 19th June 2012. The RCTs were small (16–101 breast cancer survivors); mean BMI was ≥25 and the mean age in 8 out of 9 RCTs was approximately 50 years. Five RCTs reported statistically significant effects of physical activity on insulin, IGF-I, IGF-II and IGFBP-3 in breast cancer survivors, but the results were not consistent. None of four RCTs found any evidence for a role of investigated interleukines. One trial reported some evidence that exercise may decrease C-reactive protein levels. In conclusion, available RCTs have produced some evidence that physical activity may result in beneficial changes in levels of insulin, IGFs, IGFBPs, and inflammatory biomarkers in breast cancer survivors. However, further larger RCTs on physical activity and biomarkers in breast cancer survivors are warranted.     

Menopausal hormone therapy (HT) in patients with breast cancer

OBJECTIVES: To assess the effect of menopausal hormone therapy (HT) on reoccurrence, cancer-related mortality, and overall mortality after a diagnosis of breast cancer. METHODS: We performed a quantitative review of all studies reporting experience with menopausal HT for symptomatic use after a diagnosis of breast cancer. Rates of reoccurrence, cancer-related mortality, and overall mortality were calculated in this entire group. A subgroup analysis was performed in studies using a control population to assess the odds ratio of cancer reoccurrence and mortality in hormone users versus non-users. RESULTS: Fifteen studies encompassing 1416 breast cancer survivors using HT were identified. Seven studies included a control group comprised of 1998 patients. Among the 1416 HT users, reoccurrence was noted in 10.0% (95% CI: 8.4-11.6%). Cancer-related mortality occurred at a rate of 2.6% (95% CI: 1.8-3.7%), while overall mortality was 4.5% (95% CI: 3.4-5.8%). Compared to non-users, patients using HT had a decreased chance of reoccurrence and cancer-related mortality with combined odds ratio of 0.5 (95% CI: 0.2-0.7) and 0.3 (95% CI: 0.0-0.6), respectively. CONCLUSIONS: In our review, menopausal HT use in breast cancer survivors was not associated with increased cancer reoccurrence, cancer-related mortality or total mortality. Despite conflicting opinions on this issue, it is important for primary care physicians to feel comfortable medically managing the increasing number of breast cancer survivors. In the subset of women with severe menopausal symptoms, HT options should be reviewed if non-hormonal methods are ineffective. Future trials should focus on better ways to identify breast cancer survivors who may safely benefit from HT versus those who have a substantial risk of reoccurrence with HT use.     

Dairy products and breast cancer: the IGF-I, estrogen, and bGH hypothesis

Research on the role of dietary factors in breast cancer causation has focused predominantly on fat intake. While some studies have examined associations between breast cancer rates and consumption of whole milk, there has been less attention given to dairy products in general. Dairy products contain both hormones and growth factors, in addition to fat and various chemical contaminants, that have been implicated in the proliferation of human breast cancer cells. This literature review evaluates the epidemiological and mechanistic evidence linking dairy consumption with breast cancer risk.     

Nutritional fats and the risk of type 2 diabetes and cancer

Dietary factors are important predictors for the risk of diabetes type 2. Increased consumption of fibre-rich foods, fruits and vegetables as well as limited amounts of total and saturated fats are essential elements in the prevention of diabetes type 2. The association between these dietary factors and the appearance of diabetes was not only present in cohort studies but were also major elements in the dietary part of the two large diabetes prevention trials (Finnish Diabetes Prevention Study, Diabetes Prevention Program). There is also strong evidence for a relation between obesity and total fat intake and the incidence of certain types of cancers. There is a significant correlation between total fat intake and the risk of cancer; however, it is much weaker than that of the effect of red meat. Recommendations to decrease red meat intake, particularly processed meat, may decrease the risk of colorectal and prostate cancer and may have beneficial effects on breast cancer as well, although this evidence is less compelling. Overall, recommendations focused on controlling or reducing body weight by regular physical activity and avoidance of excessive energy intake from all sources, particularly from fat and saturated fats, by increasing consumption of fibre-rich carbohydrates, vegetables and fruits are effective in decreasing the risk for type 2 diabetes by more than 50% in high-risk individuals. Similar dietary patterns are likely to diminish the manifestation of certain forms of cancers. These conclusions are in agreement with current recommendations for cancer prevention as propagated by the American Cancer Society.     

Relation between breast cancer mortality and screening effectiveness: systematic review of the mammography trials

The mammography screening trials have shown varying results. This could be because screening was better in some trials than in others at advancing the time of diagnosis. If so, more cancers would be identified in such trials relative to the control group, and fewer of the cancers would have reached an advanced stage. I performed a systematic review of the mammography screening trials using metaregression. Finding many cancers was not related to the size of the reduction in breast cancer mortality (p = 0.19 after seven and p = 0.73 after 13 years of follow-up). In contrast, finding few cancers in stage II and above predicted a larger reduction in breast cancer mortality (p = 0.04 and p = 0.006). This expected association was also found for node-positive cancers (p = 0.008 and p = 0.04). However, a screening effectiveness of zero (same proportion of node-positive cancers in the screened group as in the control group) predicted a significant 16% reduction in breast cancer mortality after 13 years (95% confidence interval, 9% to 23% reduction). This can only occur if there is bias. Further analyses uncovered bias in both assessment of the cause of death and of the number of cancers in advanced stages. Consequently, the differences in the reported reductions in breast cancer mortality cannot be explained by differences in screening effectiveness. Given that the size of the bias was similar to the estimated screening effect, screening appeared ineffective.     

Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women

BACKGROUND. The rates of colon cancer in various countries are strongly correlated with the per capita consumption of red meat and animal fat and, to a lesser degree, inversely associated with the consumption of fiber. METHODS. We conducted a prospective study among 88,751 women 34 to 59 years old and without a history of cancer, inflammatory bowel disease, or familial polyposis who completed a dietary questionnaire in 1980. By 1986, during 512,488 person-years of follow-up, 150 incident cases of colon cancer had been documented. RESULTS. After adjustment for total energy intake, animal fat was positively associated with the risk of colon cancer (P for trend = 0.01); the relative risk for the highest as compared with the lowest quintile was 1.89 (95 percent confidence interval, 1.13 to 3.15). No association was found for vegetable fat. The relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 (95 percent confidence interval, 1.24 to 5.03), as compared with those reporting consumption less than once a month. Processed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk. The ratio of the intake of red meat to the intake of chicken and fish was particularly strongly associated with an increased incidence of colon cancer (P for trend = 0.0005); the relative risk for women in the highest quintile of this ratio as compared with those in the lowest quintile was 2.49 (95 percent confidence interval, 1.50 to 4.13). A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but this relation was not statistically independent of meat intake. CONCLUSIONS. These prospective data provide evidence for the hypothesis that a high intake of animal fat increases the risk of colon cancer, and they support existing recommendations to substitute fish and chicken for meats high in fat.     

Obesity: Focus on all-cause mortality and cancer

Excess body weight is a strong determinant as well as modifiable risk factor for all-cause and cancer mortality, and as such carries the potential for primary prevention. Recently published studies greatly enhance our knowledge about the impact of body fat distribution on relative risks specific to cancer type, and among women, there is further evidence for the role of menopausal status in modifying relative risks. However, the magnitude of all-cause as well as cancer mortality related to excess body weight varies between prospective cohort studies and the strength of the association, in particular in the overweight range, is still a matter of debate. The distribution of total body fat, how we measure it, and the ratio of body fat to fat-free mass explains to some degree the inconsistencies in associated disease risks in the literature. Physical activity, a potential confounder, has been shown to lower the risk of many chronic diseases, independently of the degree of adiposity. A review of the literature provides much support for public health messages that advocate the benefit of change to a more active lifestyle regardless of age and level of excess body fat.     

Insulin resistance, obesity and breast cancer risk

Breast cancer (BC) is one of the most important problems of public health. Among the avoidable risk factors during a woman's life, overweight and obesity are very important ones. Furthermore they are increasing worldwide. The risk of breast cancer is traditionally linked to obesity in postmenopausal women; conversely, it is neutral or even protective in premenopausal women. Since the initiator and promoter factors for BC act over a long time, it seems unlikely that the menopausal transition may have too big an impact on the role of obesity in the magnitude of the risk. We reviewed the literature in an attempt to understand this paradox, with particular attention to the body fat distribution and its impact on insulin resistance. The association of insulin resistance and obesity with BC risk are biologically plausible and consistent. Estradiol (E2) and IGFs act as mitogens in breast cancer cells. They act together and reciprocally. However the clinical and biological methods to assess the impact of insulin resistance are not always accurate. Furthermore insulin resistance is far from being a constant feature in obesity, particularly in premenopausal women; this complicates the analysis and explains the discrepancies in large prospective trials. The most consistent clinical feature to assess risk across epidemiological studies seems to be weight gain during lifetime. Loss of weight is associated with a lower risk for postmenopausal BC compared with weight maintenance. This observation should be an encouragement for women since loss of weight may be an effective strategy for breast cancer risk reduction.     

Correlation of body mass index and leptin with tumor size and stage of disease in hormone-dependent postmenopausal breast cancer: preliminary results and therapeutic implications

Obesity is considered the most important risk and prognostic factor for estrogen-dependent breast cancer in postmenopausal women. Adipokines, in particular leptin, are at the center of the etiopathogenetic mechanisms by which obesity and related metabolic disorders influence breast cancer risk and its prognosis. The present prospective observational study aims to investigate the relationship between body mass index (BMI), serum levels of leptin and proinflammatory cytokines, and breast cancer prognostic factors. In the study, 98 postmenopausal and 82 premenopausal patients with ER-positive breast cancer participated. During the same study period, 221 control subjects were simultaneously recruited. Women underwent baseline measurements pre-operatively, before any surgical and systemic treatments. Pathologic characteristics of tumors were abstracted from pathology reports. Leptin and proinflammatory cytokines were assayed in stored fasting blood specimens. In postmenopausal breast cancer patients, BMI, leptin, and interleukin-6 significantly correlated with pathological tumor classification (pT) and TNM stage. Multivariate regression analysis showed that BMI and leptin, but not interleukin-6, were independent predictive variables of pT and TNM stage. Our results seem to suggest a twofold role of leptin in the etiopathogenesis of postmenopausal estrogen-positive breast cancer. Indeed, leptin reflects the total amount of fat mass, which correlates to aromatase activity and subsequent estrogens levels. Further studies are warranted to clarify the role of leptin and interleukin-6 in breast carcinogenesis and identify new therapeutic options, beyond the use of aromatase inhibitors, acting selectively on adipokine-driven pathways.     

Phytoestrogens and post reproductive health

The use of phytoestrogens for various perceived health benefits is widespread. Despite 20 years of research the evidence for any significant health benefits remains inconclusive. Pre clinical trials have demonstrated both non-genomic and genomic actions of constituents of phytoestrogens including selective, but weak, binding to estrogen receptors, with a preference for ER B over ER A. Evidence of clinically relevant biological effects from observational studies and randomized trials has, in general, been lacking. Despite many trials there remains little evidence that phytoestrogens, whether dietary or supplemented, significantly relieve menopausal vasomotor symptoms or cognition. Several potential mechanisms for a positive effect on bone and cardiovascular health have been demonstrated however no fracture prevention data or cardiovascular end point benefit has yet been demonstrated. In vitro effects of phytoestrogens on breast cells have been both stimulatory and inhibitory however net effects appear neutral with observational studies finding no change in breast cancer risk. No effect has been seen on endometrial or other cancers and side effect profiles have, in general, been mild.     

Vitality, mental health, and satisfaction with information after breast cancer

OBJECTIVE: The purpose of this study was to investigate the relationship between satisfaction with information about treatment-related and survivorship issues and mental health outcomes, including vitality, in long-term breast cancer survivors. METHODS: Participants who had finished treatment for breast cancer at least 3 months before enrollment completed a survey instrument designed to evaluate satisfaction with diagnostic and treatment information and satisfaction with survivorship information. Mental health and vitality were measured using the Medical Outcomes Study SF-36, and distress was measured using the impact of events scale. Bivariate analyses and linear regression analyses were performed to investigate the relationships between satisfaction with information, mental health, vitality, and distress controlling for clinical and treatment variables. RESULTS: The survey was completed by 231 participants (response rate 83%). More respondents were highly satisfied with treatment information (87%) than with survivorship information (30%, p=0.0001). There was a strong positive relationship between satisfaction with information (both treatment and survivorship issues) and vitality, mental health, and a strong negative relationship with distress. In multivariate analyses, satisfaction with treatment information was independently associated with mental health (p<0.01), and satisfaction with survivorship information was independently associated with vitality (p<0.05). CONCLUSION: Among patients who have completed treatment for breast cancer, satisfaction with diagnosis and treatment information is greater than satisfaction with survivorship issues and satisfaction with information may play an important role in mental health outcomes. PRACTICE IMPLICATIONS: Given the relationship between satisfaction with information and vitality, interventions to improve informational support regarding survivorship issues are warranted.     

Adipokines,Inflammation, and Adiposity in Hematopoietic Cell Transplantation Survivors

Adult survivors of acute leukemia in childhood have a higher-than-expected frequency of obesity and are at increased risk for metabolic syndrome and early mortality from cardiovascular disease (CVD). Adipose tissue has been recognized as an endocrine and paracrine organ that secretes various adipokines involved in metabolic regulation and inflammatory processes. In this study, we examined inflammatory factors (IL-6 and TNF-α) and adipokines (adiponectin, leptin), in addition to body composition and adiposity, in cancer survivors who underwent hematopoietic cell transplantation (HCT) during childhood compared with sibling controls. Over 2-year survivors of HCT for hematologic malignancies during childhood were recruited from 2 institutions along with a control population of siblings. Participants underwent evaluation for body composition, anthropometric measurements, and assessment of CVD risk factors and adipokines. Cases were stratified by radiation exposure in the preparative regimen (total body irradiation [TBI]?+?central nervous system [CNS] irradiation, TBI only, chemotherapy only) and adjusted least squares means were estimated for each adipokine and adjusted by age, sex, race, Tanner stage, and percent fat mass (PFM) percentiles (0-24, 25-74, 75+). A total of 151 HCT survivors and 92 siblings underwent evaluation. Significant differences in mean adipokine levels were detected between survivors and siblings; leptin was significantly higher and adiponectin significantly lower in HCT survivors who received TBI with or without CNS irradiation compared with siblings. IL-6 was significantly higher in all groups of HCT survivors compared with siblings. Body mass index (BMI) was similar in survivors and controls, although PFM was significantly higher in all groups of HCT survivors and lean body mass (LBM) was lower in survivors who received TBI with or without CNS radiation compared with siblings. HCT survivors showed an unfavorable profile of inflammation, adipokines, and adiposity, despite similar BMI as controls. Higher PFM and lower LBM may contribute to these findings. TBI exposure is correlated with greater severity of these observations. Increasing LBM may represent a tangible target for mitigating the high cardiometabolic risks of HCT survivors.     

Phytoestrogens and breast cancer in postmenopausal women: a case control study

OBJECTIVE: To examine the association between isoflavones, androgens, and dietary composition and the risk of breast cancer in Australian postmenopausal women. DESIGN: Eighteen women with recently diagnosed breast cancer before surgery and 20 controls were recruited over a 12-month period. Both cases and controls were similarly assessed for urinary isoflavones, serum and urinary sex steroids, and dietary intake. RESULTS: Women with breast cancer had lower 24-h urinary daidzein compared with controls (cases: 31 [95% CI: 4, 234] nmol/day; controls: 427 [95% CI: 4, 234] nmol/day; p = 0.03), and there was a trend to lower urinary genistein excretion (cases: 25 [95% CI: 5, 132] nmol/day; controls: 155 [95% CI: 43, 550] nmol/day; p = 0.08). Total testosterone was higher in women with breast cancer compared with controls (cases: 1.3 [95% CI: 1.1, 1.5] nmol/L; controls: 1.0 [95% CI: 0.8, 1.11 nmol/L; p = 0.05). No significant differences were found for serum sex hormone binding globulin, free androgen index, dehydroepiandrosterone sulphate, estradiol and progesterone, or in urinary androgen metabolites, or in dietary intake with regard to fat, carbohydrate, protein, or fiber consumption between cases and controls. CONCLUSIONS: This preliminary study is the first report of low urinary daidzein and genistein in postmenopausal women with breast cancer. These findings are in keeping with the increasing observational data demonstrating a protective effect from phytoestrogens on breast cancer risk.     

Roundtable discussion: Dietary fats in prevention of atherosclerotic cardiovascular disease

This roundtable discussion on dietary fats was inspired by a recent Presidential Advisory from the American Heart Association giving recommendations about dietary fats for prevention of atherosclerotic cardiovascular disease. The Advisory clarifies a long-held position that saturated fat should be reduced in the American diet. New studies and meta-analyses have questioned the adverse role of saturated fat. The Advisory adds a crucial clarification based primarily on 4 randomized controlled diet trials, each conducted over 4 to 8 years during the 1960s extending to the 1970s. In each trial, saturated fat was reduced and replaced by vegetable oil rich in polyunsaturated fat (PUFA). Meta-analysis showed 29% reduction in major coronary events in the groups receiving PUFAs. Randomized clinical trials provide the best kind of evidence. Replacing saturated fat with PUFA reduces cardiovascular events. Replacing saturated fats with carbohydrates or trans fats does not reduce cardiovascular events. Cardiovascular risk reduction has also been seen in randomized trials with monounsaturated fat in the context of whole food diets, mostly plant based (Mediterranean diets). In this discussion, we additionally cover some of the roller-coaster history of recommendations concerning dietary fat and provide advice for practical counseling.     

Controversy between estrogen replacement therapy and risk of breast cancer in menopause

At present, no information is available from controlled prospective randomized clinical trials to demonstrate a causal link between estrogen replacement therapy (HRT) and the risk of developing breast cancer. In most epidemiologic studies, HRT is not associated with an major increased risk of breast cancer; thus for women who had used estrogen for 10 years or more, the relative risk of breast cancer is 1.46 which is considered as small magnitude. Clinicians and patients are challenged with the difficult task of balancing the beneficial effects of HRT on cardiovascular and bone disease with the potential adverse effects on the breast. The analyses of the benefits and risks of HRT generally indicate that the benefits of therapy outweigh the risks. In other respect the number of survivors of breast cancer are increasing rapidly because of both early detection and the availability of more effective treatments. This effect will increase the number of hypoestrogenic survivors of breast cancer, a group that might benefit from HRT. However, the decision of using HRT has to be determined between the patient and the physician.     

Postmenopausal hormone therapy and the risk of breast cancer: the view of an epidemiologist

OBJECTIVES: Postmenopausal hormone therapy (PMH) has been widely used by menopausal women living in western countries for the past several decades. Numerous studies have evaluated the relationship between PMH and breast cancer risk because steroid hormones have been implicated in breast cancer etiology. METHODS: A review of selected studies was performed to evaluate the history of investigations of the association between PMH and breast cancer, with a focus on studies evaluating different PMH regimens and different histologic types of breast cancer. RESULTS: Though studies conducted before the early 1990s suggest that both combined estrogen and progestin (E + P) PMH and unopposed estrogen (E) PMH are associated with an increased risk of breast cancer, more recent observational studies suggest that E + P, particularly current use for 5 years or longer, is more strongly associated with breast cancer risk than is unopposed E. Results from the Women's Health Initiative (WHI) randomized trials have confirmed these findings as they indicate that E + P is causally related to breast cancer (relative risk (RR) = 1.24; 95% confidence interval (CI): 1.01-1.54), while E alone is not (RR = 0.77; 95% CI: 0.59-1.01). CONCLUSIONS: There is clear and consistent evidence that use of E + P increases a woman's risk of breast cancer. Alternatively, current evidence suggests that use of unopposed E is not as strongly associated with breast cancer risk. Further studies are needed though to examine how different PMH regimens, doses, and methods of delivery are related to breast cancer risk, and how PMH impacts the risks of different types of breast cancer.     

Dietary factors and vasomotor symptoms in breast cancer survivors: the WHEL Study

OBJECTIVE: Vasomotor symptoms (VMS)(hot flashes, night sweats) are associated with natural or surgically or chemotherapy-induced menopause, the latter occurring frequently in women treated for breast cancer. To manage VMS, some women seek alternatives to menopausal hormone therapy, such as supplements or modified food choices. The objective of the present analyses was to assess associations of VMS occurrence and change in severity of VMS over 12 months with dietary intakes of fiber, fat, and selected soy-containing foods, and use of phytoestrogen or vitamin E supplements in women with recent early stage breast cancer, adjusting for covariates. DESIGN: Using multivariate logistic regression, data were analyzed from 2,198 women with early-stage breast cancer who enrolled 2 to 48 months after diagnosis in the Women's Healthy Eating and Living randomized, controlled trial of a high-vegetable, high-fiber, reduced-fat diet. RESULTS: Being peri- or postmenopausal, using tamoxifen, having low social support or depressive symptoms, and using vitamin E or phytoestrogen supplements were significantly associated cross-sectionally with reporting moderate/severe VMS at enrollment. Increased symptom severity after 12 months was significantly associated with higher body mass index, tamoxifen use, and smoking. Decreased symptom severity at 12 months was significantly associated with high dietary fiber intake; no decrease was observed in women who were peri- or postmenopausal, using tamoxifen, or had low fat intake or low social support. CONCLUSIONS: High dietary fiber intakes, premenopausal, and high social support were related to decreased severity of VMS 1 year after study enrollment in women recently treated for breast cancer.     

Effects of estrogens and hormone replacement therapy on breast cancer risk and on efficacy of breast cancer therapies

This review summarises preclinical and clinical data on effects of endogenous and exogenous estrogens on probability of breast cancer diagnosis, and on the course and efficacy of breast cancer therapies. The data indicate that higher endogenous estrogen exposure (e.g. pregnancy, early menarche and late menopause, estrogen levels in future breast cancer patients, obesity) or exogenous estrogens (oral contraceptives; hormone replacement therapies) may be associated with an increased probability of breast cancer diagnosis. However, there is little evidence that estrogens have deleterious effects on the course of breast cancer. Moreover, increased incidence of breast cancer diagnosis after prolonged hormone replacement therapy (HRT) use seems to be associated with clinically less advanced disease. In studies assessing both diagnosis and mortality, HRT is frequently associated with reduced mortality compared to never users. The interaction of progestagens and estrogens on the probability of breast cancer diagnosis is complex and dependent on type of progestagens and regimens employed. Efficacy of current treatment modalities for breast cancer (surgery, irradiation, adjuvant therapy or chemotherapy) is not negatively influenced by estrogens at concentrations considerably higher than those attained with current HRT preparations. Although it cannot be excluded that estrogens increase the probability of breast cancer diagnosis, available data fail to demonstrate that, once breast cancer has been diagnosed, estrogens worsen prognosis, accelerate the course of the disease, reduce survival or interfere with the management of breast cancer. It may therefore be concluded that the prevalent opinion that estrogens and estrogen treatment are deleterious for breast cancer, needs to be revisited. However, results of ongoing prospective, randomised clinical trials with different HRT regimens in healthy women or breast cancer survivors are needed to provide more definite conclusions about risks and benefits of HRT.