Caroline Antoine

Postmenopausal hormone therapy: risks and benefits.

Postmenopausal hormone therapy (PMHT) is used for the relief of menopausal symptoms, but the dosage has varied greatly throughout its existence. By the end of the 1990s, PMHT was mainly used to prevent chronic diseases such as osteoporosis, coronary heart disease and dementia, and large prevention trials were undertaken in this context. Following the initial negative reports of these trials, use of PMHT dramatically decreased. These reports noted surprisingly increased risks, notably of coronary heart disease, stroke and breast cancer, in people who used PMHT. Nowadays, considering the currently available data, it seems that an important distinction should be made between the treatment of climacteric symptoms in young, generally healthy, postmenopausal women and the prevention of chronic diseases in elderly women. PMHT seems to be beneficial and safe for postmenopausal symptomatic women aged <60 years. Treatments with a high safety profile should be the preferred option, including low-dose PMHT, oestrogen-only therapy in women who have had a hysterectomy, and vaginal oestrogen therapy for women with atrophic vaginitis. Nonandrogenic progestin might have a reduced thrombotic and breast cancer risk, and transdermal oestrogen could have a reduced thrombotic risk. Nevertheless, PMHT should not be used for the prevention of chronic diseases in the elderly (>70 years old) owing to the increased risk of stroke and breast cancer in these patients.

Safety of alternative treatments for menopausal symptoms after breast cancer: a qualitative systematic review

Aim This qualitative review analyzes systematically the safety of drugs used to alleviate menopausal symptoms, other than hormone replacement therapy, in breast cancer patients. Methods We searched systematically studies using tibolone, serotonin reuptake inhibitors, clonidine, veralipride, gabapentin, black cohosh and phytoestrogens in breast cancer patients. We selected five studies for which we evaluated the methodology, characteristics of the studied populations, outcomes in terms of mortality and recurrence rates. Results Four trials were conducted using tibolone in breast cancer patients: one double-blind, randomized trial, one prospective controlled study, and two uncontrolled studies. They considerably lack power to detect any difference in breast cancer recurrence or mortality between the treated and control patients. Similar conclusions have to be drawn from the only controlled retrospective study analyzing the safety of antidepressants and antihistamines. We were unable to find studies reporting the safety of the other drugs in breast cancer patients. Conclusions There are no valuable data indicating the absence of a harmful effect of drugs used to alleviate climacteric symptoms in breast cancer patients. There is a need for randomized trials to assess the safety of these drugs. In the meantime, patients should be informed about the absence of safety data.

A survey among breast cancer survivors: treatment of the climacteric after breast cancer

Aim To evaluate the prevalence and type of menopausal treatments used by breast cancer survivors. To assess factors that impaired the quality of life of these patients. Material and methods A questionnaire assessing quality of life was sent to 325 breast cancer patients. A 66% valid response rate was obtained. Among these responses, 169 women were postmenopausal. The following results concern these patients only. Results Forty-five women were using some treatment to alleviate certain menopausal symptoms (26.6%). More than half of the patients used no therapy to alleviate menopausal symptoms, either because they had no symptoms (n = 43; 25.4%), they feared breast cancer recurrence (n = 24; 14.2%), they were advised not to use a treatment (n = 27; 16%), it had been shown to be inefficient (n = 5; 3%), or because of contraindication (n = 3; 1.8%). In this survey, 62.3% of postmenopausal women affected by breast cancer suffered from hot flushes (n = 94), of which half were severe (n = 46). Among women suffering from hot flushes, a third used various products to alleviate their symptoms (n = 30). Younger women suffered more often from vasomotor symptoms than did older women (p < 0.000). Current users of aromatase inhibitors suffered more from sexual disorders than did non-users (p < 0.001). They had more often an unsatisfactory sexual life (p < 0.01), more vaginal dryness (p = 0.01) and a decreased libido (p < 0.02) compared to non-users. Conclusion More than 50% of postmenopausal women suffered from climacteric symptoms such as hot flushes, but few were taking a treatment to alleviate these symptoms.

Improving quality of life after breast cancer: prevention of other diseases

Many women with breast cancer will be diagnosed at an early stage through screening programmes. Furthermore, most women affected by breast cancer will not die from it but from other diseases, owing to recent improvements in treatment. This article assesses whether breast cancer survivors suffer more frequently from other diseases. Specifically, it examines whether they have a higher incidence of other cancers, cardiovascular events and osteoporotic fractures. Women with breast cancer and three or more co-morbid conditions have a 20-fold higher rate of mortality from causes other than breast cancer and a 4-fold higher rate of all-cause mortality when compared with patients who have none. Breast cancer survivors are at increased risk of other cancers, such as stomach, colorectal and lung. Radiotherapy, trastuzumab and aromatase inhibitors increase the risk of cardiovascular disease. However, tamoxifen does not, although it is associated with an increased risk of venous thromboembolism. Aromatase inhibitors, but not tamoxifen, increase the risk of osteoporotoic fracture and bisphosphonate therapy should be considered.

Systematic review about breast cancer incidence in relation to hormone replacement therapy use.

Abstract Background Several studies report a decrease in breast cancer incidence subsequent to the decrease in hormone replacement therapy (HRT) use. But its magnitude and the time-lag may vary between countries. This may reflect differences in populations, previous type and prevalence of HRT use and breast cancer screening. Aim To review systematically studies assessing the relation between breast cancer incidence and change of HRT use. Material and method Descriptive analysis of the methodology of the studies including design limitations and presence of confounding factors, data sources for breast cancer and HRT and regimens of HRT used. Results and discussion Eighteen articles were selected. Most studies were ecological and confounding factors such as mammography screening and changes in reproductive and lifestyle habits could not be excluded. Sources of data on breast cancer and HRT were heterogeneous and only few data on HRT regimens used were available. Most studies concluded that the decrease in HRT use during the last decade was probably associated with a decrease in breast cancer incidence, especially for women aged 50 years or more. Conclusions Data, mostly from epidemiological studies, suggest that the decrease in breast cancer incidence can be partly attributed to the drop in HRT use. Nevertheless, available studies are hampered by a number of limitations and it remains difficult to evaluate the exact impact of the drop in HRT use on the decrease in breast cancer incidence. Especially, the studies are seldom based on detailed individual data and do not provide information on regimens used, type of cancers and possible confounding factors.

Update of the evolution of breast cancer incidence in relation to hormone replacement therapy use in Belgium

BACKGROUND Several studies reported a decrease in breast cancer (BC) incidence, subsequent to the decrease in hormone replacement therapy (HRT) use. AIM Although Belgium has one of the highest incidences of BC in Europe and one of the highest rates of HRT use, we were unable, in a previous study, to observe a significant association between BC incidence and HRT changes. In this updated report we added the BC data from incidence years 2007 and 2008. MATERIAL AND METHOD We used European standardized incidence rates for invasive BC in the age class 50-69 years for Flanders (1999-2008), Brussels and Wallonia (2004-2008), obtained from IMS Health HRT sales data (1997-2008) for Brussels, Flanders and Wallonia. The association between BC incidence and HRT use was analyzed using generalized estimating equations (GEE) in order to take into consideration the dependency between the subsequent data points. RESULTS There was a significant association between the invasive BC incidence rate and estimated rate of HRT users in the previous year: p-value<0.001. CONCLUSION Although this study is hampered by a number of limitations, these data support the idea that the drop in BC incidence can be partly attributed to the decrease in HRT use. Since HRT remains the most used medication for climacteric symptoms, we encourage the creation of a prospective registry in Europe, collecting detailed data in various European countries, in order to assess the adjusted increase in BC risk associated with HRT, which may be population and regimen dependent.

Menopausal hormone therapy use in relation to breast cancer incidence in 11 European countries

INTRODUCTION The use of menopausal hormone therapy (MHT) has decreased in many countries in the past 10 years. This is a consequence of the initial publication of the results of the Womens Health Initiative (WHI) randomized trial of estrogen plus progestin. In various countries, further studies then analyzed the incidence of breast cancer (BC) in relation to changes in MHT use. Some reported a decreased BC incidence following cessation of MHT, but others did not. This may reflect differences in BC incidence, in MHT use or in confounding factors, but also in study methodology. AIM To analyze the changes in BC incidence and MHT use, using the same methodology, in 11 European countries. MATERIALS & METHOD We limited the study to women between the ages of 45 and 69. BC incidence data were provided from cancer registries. MHT sales data were extracted from health sales databases for the years 2003-2013. The association between BC incidence and the rate of MHT use during the past year in Europe was assessed using linear mixed models. RESULTS A drop in MHT sales was consistent in all countries for the whole period of follow-up. This was not the case for BC incidence. We found no evidence of a relation between BC incidence and MHT sales in the past year, except for sales of tibolone. CONCLUSIONS The longer observation period did not confirm the results of studies that had a shorter follow-up, except in relation to tibolone. The role of confounding factors needs to be clarified.

Treatment of climacteric symptoms in breast cancer patients: A retrospective study from a medication databank

INTRODUCTION Women affected by breast cancer (BC) will often go through menopause at an earlier age and display more frequent and severe symptoms than women who have a natural menopause. The safety of hormone replacement therapy (HRT) and vaginal estrogens for BC survivors has been debated over time and remains unclear. Non hormonal therapies such as antidepressants, gabapentine and clonidine may be useful for those patients but there are few data about their safety. AIM This retrospective study analyses the use by BC patients of treatments known to alleviate climacteric symptoms. MATERIAL AND METHOD Post-menopausal Estrogen Receptors positive (ER+) BC patients, aged 45-69, were identified as having bought, at least once, an aromatase inhibitor (AI) or tamoxifen between the years 2000 and 2012 through a pharmaceutical databank in Belgium. Among them, we defined users of a climacteric treatment those who bought, at least once, HRT, vaginal topical estrogens, antidepressants, clonidine and gabapentine. RESULTS We identified 2530 BC patients. Among them, 45% were buying a treatment known to alleviate menopausal symptoms. The majority of these treatments were non-HRT therapies. HRT and vaginal estrogens were seldom bought (respectively 1.1% and 6%), but 3% bought vaginal estrogens while buying AI. About 9.2% of tamoxifen users patients bought antidepressants implicated in tamoxifen metabolism at the same time as tamoxifen. CONCLUSIONS Most BC patients follow current guidelines contra-indicating the use of HRT after BC, they use non hormonal therapies. In some cases they use unfortunately antidepressants that may alter the metabolism of tamoxifen.

Evolution of breast cancer incidence in relation to hormone replacement therapy use in Belgium

Background Recent randomized studies concluded that an increased risk of breast cancer is associated with hormone replacement therapy (HRT). Since then, HRT use has decreased in many countries. Several studies have reported a subsequent decrease in breast cancer incidence. Aim As Belgium has one of the highest incidences of breast cancer in Europe and has a high rate of HRT use, with differences between regions, we assessed the evolution of breast cancer incidence and HRT sales per region and per regimen. Materials and methods Breast cancer incidence rates (provided by the Belgian Cancer Registry) and HRT sales data (provided by IMS Health®) were analyzed by region, age class and HRT regimens. We also calculated the correlation between breast cancer incidence and HRT sales. Results Breast cancer incidence decreased from 2003 onwards in Flanders, Brussels and Wallonia, especially in the age group 50–69 years. In the same three regions, HRT use decreased by half from 2002 onwards. Greater decreases were observed for estrogens combined with androgenic progestins, estrogens only and estrogens prescribed with a separate progestin. The correlation between breast cancer incidence rates and HRT sales in the previous year was 0.55 (p = 0.04), but, when adjusted for the number of women in the age class 40–69 years in each region, the correlation was no longer statistically significant (r = 0.39, p = 0.17). Conclusion Although many arguments support the hypothesis that the drop in breast cancer incidence can be partly explained by the decrease in HRT use, we were unable to find a strong association between the two in Belgium.

Treatment of Premature Menopause in Breast Cancer Patients

Abstract Premature menopause occurs frequently in breast cancer patients (BC), but there are no specific data about its management. Although hormone therapy (HT) is very efficient in relieving menopausal symptoms, the prescription of this type of drug is still not indicated for BC patients, since in one randomized study (of two existing) an increased rate of new breast cancer (BC) occurrence in HT users was reported. The efficacy of other medications, such as serotonin re-uptake inhibitors, clonidine, veralipride, gabapentin, is much lower than that of HT. The efficacy of black cohosh and phyto-oestrogens remains to be proven. The safety of medications other than HT has not been established either in BC patients. There is a need for randomised trials assessing the safety of these drugs. In the meantime, patients should be informed about the absence of safety data. Prevention and treatment of urogenital atrophy is achieved by using vaginal moistures and weak oestrogen topical preparations. Prevention and treatment of osteoporosis is achieved by a healthy life style, adequate calcium and vitamin D intake and if necessary biphosphonate therapy.