Hormone replacement therapy in women with a history of breast cancer

Health care professionals in modern Western societies will meet an increasing number of women surviving breast cancer. How the menopause of these women should be treated is still an open question. Use of hormone replacement therapy (HRT) may, at least in theory, increase the risk for recurrence of cancer, but its categoric refusal is a double-edged sword because it also denies these women all the undisputable health benefits HRT provides. This refusal is not, however, supported by the observational data available so far on this question, because HRT has not increased the risk for breast cancer recurrence. In fact, it is well established that HRT abolishes hot flushes and improves significantly these patients' quality of life. At present, we have no effective nonhormonal alternatives for the control of vasomotor symptoms, and the efficacy of phytoestrogens in the treatment of menopausal symptoms is unproven. Selective estrogen receptor modulators (SERMs) which protect against osteoporosis and perhaps also against breast cancer, and which may have beneficial effects on the cardiovascular system, aggravate hot flushes and are therefore not useful, at least in the first postmenopausal years. In some countries, progestins are often prescribed for the control of such patients' vasomotor symptoms, but their safety has never been assessed in clinical trials, and in theory they can be harmful. Randomized clinical trials (RCT) on the use of HRT in breast cancer survivors are underway, but their completion will take years, and even these may be open to criticism. Tibolone may appear to be an appealing alternative for HRT, but it should also be studied with RCTs in this indication. At present, a patient with a history of breast cancer must be given balanced information as to the possible benefits and risks of HRT, and she herself must make the decision whether or not to start HRT.     

Hormone replacement therapy in women with past history of endometriosis.

Endometriosis is a common clinical condition and its treatment will often lead to an estrogen deficiency status. As most of these patients are young, they will need to consider hormone replacement therapy. Endometriosis is a hormone-dependent disease and estrogen replacement can be associated with a risk of recurrence or malignant transformation. Only a few studies have addressed this problem. With the use of hormone replacement therapy (HRT), there is an increased, although undefined, risk of recurrence of endometriosis, especially in known severe cases and in obese patients. Unopposed estrogen appears to carry a higher risk than combined preparations. Delay in starting HRT after pelvic clearance is not of any benefit. After radical surgery for severe endometriosis, women often have much to gain from HRT, particularly in the early years. Benefits of HRT in terms of control of menopausal symptoms, prevention of urogenital atrophy and loss of libido and bone protection are of particular importance. HRT may still have a role in prevention of cardiovascular disease in early menopause, but this remains unproven. Although there is no firm evidence, continuous combined preparations or tibolone would appear to be the optimum choice.     

Hormone replacement therapy after breast cancer

The use of hormone replacement therapy after breast cancer is controversial. The published epidemiological studies shown no association between HRT and recurrence of breast cancer. However, the interpretation of these results is very difficult because of numerous biases in this context of observational studies. Prospective randomised trials that examine the effects of HRT in women with a history of breast cancer are currently underway in United States and in Scandinavia. The markov approach is interesting for determining the global risk-benefit balance of HRT and for visualising the effects of different risk levels on breast cancer and to compare different therapeutic strategies. Hot flushes and functional symptoms represent the essential unresolved problem of these women. The results of all these will provide valuable data to define efficient and non-deleterious approaches to improve the well being of the women after breast cancer.     

Estrogen replacement therapy in women with previous breast cancer.

OBJECTIVE: We sought to review the status of patients with breast cancer who were treated with estrogen replacement therapy and compare the results with those of nonestrogenic hormone users and women not treated with hormone replacement. STUDY DESIGN: The study group consisted of 76 patients with breast cancer, including 50 using estrogen replacement for up to 32 years, 8 using nonestrogenic hormone replacement for up to 6 years and followed for up to 11 years, and 18 using no hormones for up to 10 years. In addition to estrogen use, 40 of the 50 hormone users were treated with androgens, usually in the form of implantation of testosterone pellets. Forty-five subjects were also given progestogens, usually megestrol acetate 20 to 40 mg for 10 to 25 days each month. The 8 nonestrogen hormone users were treated with various combinations of testosterone pellets, tamoxifen, and progestogens. Forty-two of the 50 estrogen users are still being treated in our clinic, as are 2 of the 8 subjects using nonestrogen hormone. Follow-up was done through the tumor registry at University Hospital, and those whose tumor records were not current were telephoned. RESULTS: Of the 50 estrogen users, 3 have died (a mortality rate of 6%), and the rest have been followed for 6 months to 32 years, with a mean duration of follow-up of 83.3 +/- 8.81 months. One of the 8 nonestrogen hormone users has died (a mortality rate of 12.5%), and the rest have been followed for 2 to 11 years, with a mean duration of follow-up of 72.0 +/- 5. 93 months. Six of the 18 women not using hormone replacement have died (a mortality rate of 33.3%), and the rest have been followed for 6 months to 10 years, with a mean duration of follow-up of 50.5 +/- 6.01 months. CONCLUSION: Estrogen replacement therapy apparently does not increase either recurrences or mortality rates. Adding progestogens may even decrease recurrences. Women with early breast cancer should be offered hormone replacement therapy after a full explanation of the benefits, risks, and controversies.     

Hormone replacement therapy and breast cancer: a qualitative review

OBJECTIVE: To assess whether recent epidemiologic evidence supports an association between use of estrogen replacement therapy or hormone replacement therapy and risk of breast cancer. DATA SOURCES: The keywords "estrogen," "estrogen replacement therapy," or "hormone replacement therapy," and "breast cancer" or "breast neoplasm," were used to search for articles published from 1975-2000 in MEDLINE and Dialogweb. Only articles published in peer-reviewed journals and containing original data were included in this review. METHODS: Unadjusted or age-adjusted risk estimates for breast cancer among ever users of estrogen therapy compared with never users were abstracted from published articles or calculated using the data provided in the published reports. TABULATION, INTEGRATION, AND RESULTS: We found little consistency among studies that estimated the risk of breast cancer in hormone users compared with nonusers and in studies assessing the risk by duration of use. However, there was consistently a lower risk of death from breast cancer in hormone users compared with nonusers. CONCLUSION: The evidence did not support the hypotheses that estrogen use increases the risk of breast cancer and that combined hormone therapy increases the risk more than estrogen only. Additional observational studies are unlikely to alter this conclusion. Although a small increase in breast cancer risk with hormone therapy or an increased risk with long duration of use (15 years or more) cannot be ruled out, the likelihood of this must be small, given the large number of studies conducted to date.     

Hormone therapy for women after breast cancer: a review

Even though it is accepted that women with breast cancer should not receive estrogen therapy, doubts have been expressed as to the validity of this policy. In recent years opposition to this practice has been voiced more adamantly. The results of the Women's Health Initiative (WHI) study, published in July 2002, question the safety margin of estrogen therapy (ET) or hormone therapy (HT) in menopause. Whether this concern is applicable to breast cancer survivors is unclear as these women were not addressed by the study. In light of the uncertainties raised by the study and particularly the ongoing controversy about breast cancer patients, a review of the literature published prior to March 2003 was undertaken. The information gathered on the topic comes from 10 uncontrolled studies and 11 case-controlled studies, 8 retrospective and 3 prospective, carried out over the past decade. The experience encompasses 1,558 breast cancer survivors treated with ET or HT. Overall, the recurrence rate accrued from the uncontrolled studies is 7.3% (53 of 728). The average rate culminating from 11 case-controlled studies is 10.7% (99 of 830) (2.6-15.4%) in treated patients vs. 20.3% (739 of 3,640) (2.3-29.5%) in their untreated counterparts. This review revealed no increase in recurrent disease among treated patients but is not conclusive as some studies that have been flawed by biases and confounders. The fact that only 2 studies were case controlled and prospective as well as randomized, and considering concerns raised by the WHI study, it seems that many more such trials will be necessary before this controversial issue will be settled.     

Hormone replacement therapy and breast density changes.

OBJECTIVES: To compare the incidence of increased breast density and tenderness in postmenopausal women associated with transdermal (Estalis/Combipatch), Novartis, Basel, Switzerland) and oral (Kliogest), Schering AG, Berlin, Germany) hormone replacement therapy (HRT). METHODS: A total of 202 postmenopausal women were randomized to transdermal or oral HRT. Mammograms obtained at study entry and after 1 year of treatment were assessed for percent breast density by means of the digital segmentation and thresholding technique. Breast tenderness was assessed at each study visit. RESULTS: The mean breast density by ANCOVA after adjusting for screening value at study end was significantly lower for women using Estalis (38.4%, standard error 0.9%) compared with Kliogest (46.9%, standard error 1.5%) (p<0.0001). Significantly fewer women using transdermal HRT had an increase in mammographic breast density or breast tenderness compared to oral HRT. Of the women using transdermal HRT, 39.1% had no change in breast density compared to 15.7% for women using oral HRT. Only 4% of women using transdermal HRT had a marked increase in density (>25%) compared to 15.7% of women using oral HRT. Overall, 36.0% of patients in the transdermal group reported breast tenderness at some point during the 1-year study, compared with 57.6% in the oral HRT group (p=0.0002). CONCLUSION: Transdermal HRT use is associated with a significantly lower incidence of increased mammographic breast density and breast tenderness compared with oral HRT.     

子宫内膜癌激素替代治疗

子宫内膜癌(endometrial cancer,EMC)患者的激素替代治疗(hormone replacement therapy,HRT)相关研究有限,且至今为止医学界尚未对此达成统一观点。大部分妇产科医生考虑到雌激素是EMC的重要发病因素之一,并不建议给予EMC患者HRT治疗。目前认为EMC并非一定是HRT治疗的禁忌证。选择恰当的剂量和药物种类不会引起EMC的复发和死亡率增加,并可对EMC患者起到适当保护作用。HRT在提高骨密度和减轻未绝经期血管收缩症状已被证实有一定裨益,但在降低冠心病、癌症发病率,以及提高认识力和健康相关生活质量上并没有相关研究支持。由于数据有限,且大部分来自具有选择偏差的回顾性研究或小型前瞻性非随机研究,妇产科医生在评估EMC患者是否需要HRT治疗时一定要充分考虑利弊,个体化治疗。     

Hormone replacement therapy and cancer

The contribution of the tumor necrosis factor (TNF) system and leptin was studied in insulin resistance and neonatal development during the course of normal pregnancy and gestational diabetes mellitus (GDM). Thirty patients with GDM and their neonates (n = 30), 35 healthy pregnant women (15 in the first, nine in the second and 11 in the third trimester) and their neonates (n = 20), and 25 healthy matched non-pregnant women participated in the study. Significantly elevated levels of maternal TNF-α, sTNF receptor (R)-1 and R-2, leptin (detected by enzyme-linked immunosorbent assay) and fasting C-peptide (measured by radioimmunossay and raised body mass index (BMI) were found in GDM patients and in the third trimester of normal pregnancies. TNF-α, sTNFR-2, C-peptide, leptin concentrations and BMI positively correlated with each other in GDM. An inverse relationship between the body length, head circumference and body weight of the newborns, and maternal TNF-α, leptin and C-peptide concentrations was shown in GDM. In healthy pregnancies the maternal serum leptin level was in a negative linear correlation with the head circumference of the newborns. In conclusion, increased TNF-α and leptin levels may contribute to insulin resistance in GDM and in the third trimester of normal pregnancy and may negatively influence the anthropometric parameters of the newborns.     

雌激素替代治疗对生育期卵巢恶性肿瘤及宫颈癌患者预后的影响

目的观察激素替代治疗（HRT）对卵巢与宫颈恶性肿瘤预后的影响。方法1999年8月至2003年6月对广西医科大学肿瘤医院的31例卵巢恶性肿瘤和34例子宫颈癌患者术后或放疗后进行HRT。同时选择同期收治的年龄、临床期别和病理类型大致相同的44例卵巢恶性肿瘤和49例子宫颈癌作为对照。使用倍美力片或尼尔雌醇加安宫黄体酮作为HRT方法。采用Kaplan—Meier生存曲线Log-Rank分析法。COX比例风险模型．对随访数据进行分析。结果HRT和非HRT两组在各临床病理因素间相比较，差异无显著性（P〉0．05）。HRT和非HRT两组妇科恶性肿瘤复发或转移病例间相比较，差异无显著性（P〉0．05）。Kaplan-Meier生存曲线LogRank分析，两组患者的生存期比较差异无显著性（P〉0．05）。经COX比例风险模型分析，HRT不是影响生育期卵巢恶性肿瘤和宫颈癌预后的因素。结论HRT对卵巢恶性肿瘤和宫颈癌的预后无明显不良影响。     

Hormone replacement therapy in breast cancer patients: a study of 230 patients, with a case-control study

OBJECTIVES: After recalling the classical contra-indication of hormone replacement therapy (HRT) concerning patients with a personal history of breast cancer (BC), and arguments that may be opposed, the authors report the present results of a prospective study undertaken in the Center of Breast Diseases in Saint-Louis hospital in Paris since February 1992. PATIENTS AND METHODS: By April 2001, 230 patients had been included. A free interval of 2 years at least since the treatment of the primary BC has been observed. The reasons for prescribing HRT were vasomotor troubles (flushes, nightly sweats) or a dyspareunia, which were severe and not controlled by non-hormonal treatments. There was also an indication of a major osteoporotic or cardiovascular danger. In fact, many of these patients had a premature, artificial, chemo-induced menopause. The HRT most often used was an estro-progestin association (estradiol + a progestin compound) given either continuously or with a 5-d interruption each month. The mean duration of treatment was 2.5 years. RESULTS: Results, concerning the improvement of menopause troubles, were remarkable in the great majority of troubles. HRT had to be stopped in 39 cases, reading as follows: 17 cases for relapses (seven local, six in the contro-lateral breast and four metastases (7%)). Also, 22 patients (9%) interrupted their HRT for serious side-effects. A case-control study did not show any significant difference between with and without HRT patients concerning the overall survival without relapse. DISCUSSION AND CONCLUSIONS: Quality of life of patients was often substantially improved, and a deleterious effect on the cancer disease was not found. Our results are in agreement with the literature from other countries. However, one must be cautious. In such circumstances, HRT must be prescribed with the informed consent of the patients and delivered in appropriate hospital and university centers. It is wished that large randomised prospective studies may be undertaken.