Research: HRT after Breast Cancer - Part 2 _________________________________________
Maturitas. 2006 Jan 20;53(2):123-32. Menopausal hormone therapy (HT) in patients with breast cancer. Batur P, Blixen CE, Moore HC, Thacker HL, Xu M. Department of Internal Medicine, Section of Women's Health Cleveland Clinic Foundation, Crown Centre II, Independence, OH 44131, USA. firstname.lastname@example.org Abstract 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.
Gynecol Endocrinol. 2002 Dec;16(6):469-78. Hormone replacement therapy in women with a history of breast cancer. Ylikorkala O, Metsa-Heikkila M. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland. 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 indisputable 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. Int J Fertil Womens Med. 1999 Jun-Aug;44(4):186-92. An experience with estrogen replacement therapy in breast cancer survivors. Brewster WR, DiSaia PJ, Grosen EA, McGonigle KF, Kuykendall JL, Creasman WT. Division of Gynecologic Oncology, University of California Irvine Medical Center, Orange 92868, USA. OBJECTIVE: To evaluate the outcome of breast cancer patients who elected estrogen replacement therapy (ERT). STUDY DESIGN: Breast cancer survivors who elected ERT received the preferred regimen of conjugated estrogen 0.625 mg/day with medroxyprogesterone acetate 2.5 mg/day. RESULTS: 145 patients received ERT for at least 3 months. Thirteen recurrences (9%) were identified; 10 are alive with disease, 3 are dead of disease. The median interval between diagnosis and commencement of ERT was 41 months. Forty-one percent of the study group initiated ERT within 3 years of their breast cancer diagnosis. The median duration of follow-up on ERT was 30 months. CONCLUSION: The concern that ERT might activate growth in occult metastatic sites and promote a rash of recurrences was not confirmed. It is unreasonable to categorically deny all breast cancer survivors ERT. J Reprod Med. 2004 Jul;49(7):510-26.
Hormone therapy for women after breast cancer: a review Levgur M. Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY 11219, USA
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 bythe 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, 8retrospective 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 Ann Surg Oncol. 2001 Dec;8(10):828-32. Estrogen replacement therapy after breast cancer: a 12-year follow-up. Peters GN, Fodera T, Sabol J, Jones S, Euhus D. The Center for Breast Care, The University of Texas Southwestern Medical Center at Dallas, 75390-9161, USA. BACKGROUND: In the United States, estrogen replacement therapy (ERT) is discouraged in breast cancer survivors because of concerns that hormones may reactivate the disease. Because ERT can improve quality of life and decrease morbidity from osteoporosis and cardiovascular disease, however, this policy is increasingly being challenged. METHODS: From February to August 1995, 607 breast cancer survivors were interviewed concerning ERT usage. Sixty-four patients indicated they received some form of ERT after their breast cancer diagnosis. Medical records for these patients were analyzed for disease stage, surgical treatment, adjuvant treatment, estrogen and progesterone receptor status, date of initiation of ERT, type of ERT, recurrence, and final outcome. Patients receiving ERT were followed prospectively. RESULTS: Eight patients were excluded because they had used only vaginal cream ERT. The remaining 56 received ERT as conjugated estrogens, an estradiol patch, estropipate, or birth control pills. The median follow-up from diagnosis was 12.8 years (range, 4.7-38.9 years). The median time on ERT since diagnosis was 6.4 years (range, 1.0-20.9 years); 38% of the patients initiated ERT within 2 years of diagnosis. Estrogen receptors were positive in 28 (74%) of the 38 cases with available information. Pathological disease stage at time of diagnosis and treatment was 0 in 15 cases (27%), I in 27 (48%), and II in 14 (25%). Twenty-six patients (47%) received adjuvant chemotherapy or hormonal therapy. One local recurrence and one contralateral breast cancer occurred during the follow-up period (13.5 and 9.6 years, respectively), with no regional or distant recurrences, for a 15-year actuarial disease-free survival rate of 92.5%. There were no breast cancer deaths. CONCLUSIONS: Use of ERT in a cohort of breast cancer survivors with tumors of generally good prognosis was not associated with increased breast cancer events compared with non-ERT users, even over a long follow-up period. Anticancer Res. 1998 May-Jun;18(3C):2253-5. Hormone replacement therapy in women with breast cancer. Braendle W. Division of Gynecological Endocrinology and Reproductive Medicine, University Hospital, Hamburg-Eppendorf, Germany. The influence of estrogens on the growth of mammary carcinoma cell lines has been confirmed by many studies. Therefore, past or recent history of breast cancer is principally seen as a contraindication for estrogen or estrogen/progestin replacement therapy. The recently made possible early diagnosis of mammary carcinomas in many cases has resulted in a better prognosis, and means that following treatment women are living for a long time postmenopausally. Therefore, hormone replacement therapy is demanded by many patients. Recent studies with a limited number of patients, however, have shown no adverse effects of an estrogen or an estrogen-progestin replacement therapy after treatment of a mammary carcinoma. In some studies even a positive effect has been found in recurrence free survival. However, a final decision upon estrogen or estrogen/progestin replacement therapy in postmenopausal women with a history of breast cancer, cannot be made until the results of prospective clinical trials are finalized. Menopause. 2003 Jul-Aug;10(4):277-85. Estrogen replacement therapy in breast cancer survivors: a matched- controlled series. Decker DA, Pettinga JE, VanderVelde N, Huang RR, Kestin L, Burdakin JH. Department of Medicine, William Beaumont Hospital, Royal Oak-Troy, MI 48073, USA. OBJECTIVE: We prospectively administered estrogen replacement therapy (ERT) to control estrogen deficiency symptoms in breast cancer survivors as part of our clinical practice. We report the consequences of ERT compared with a historical matched-control group. DESIGN: Two hundred seventy-seven disease-free survivors received ERT. Controls were matched for exact stage, a recurrence-free period similar to the period to ERT initiation in the ERT group, approximate age, and duration of follow-up. The mean time from breast cancer diagnosis to initiation of ERT was 3.61 (+/- 0.25) years, with a median of 1.88 years. The mean duration of ERT was 3.7 (+/- 3.01) years, with a median of 3.05 years. RESULTS: Hot flashes were relieved in 206 of 223 women (92%), dyspareunia/vaginal dryness in 149 of 167 women (89%), and reactive depression/anxiety/mood change in 111 of 126 women (88%). Univariate analysis demonstrated no statistical differences between the groups for age, stage, pathology at diagnosis, progesterone receptor status, local therapy, breast at risk, prior chemotherapy, and duration of follow-up. The ERT group was more likely to be estrogen receptor negative (P = 0.01), to have received prior ERT (P < 0.001), and to have received no adjuvant tamoxifen (P < 0.001). There was no significant difference between the ERT and control groups in ipsilateral primary/recurrence (5/155 v 5/143; P = 0.85), contralateral breast cancers (10/258 v 9/260; P = 0.99), or systemic metastasis (8/277 v 15/277; P = 0.13). Noncause-specific deaths in the control group numbered 15 (of 277), and in the ERT group, 7 (of 277) (P = 0.03). Overall survival favored the ERT group (P = 0.02). CONCLUSIONS: In these selected patients, ERT relieved estrogen deficiency symptoms and did not increase the rate or time to an ipsilateral recurrence/new primary, contralateral new primary, local-regional recurrence, or systemic metastases. Am J Obstet Gynecol. 2007 Apr;196(4):342.e1-9. Reduced incidence of distant metastases and lower mortality in 1072 patients with breast cancer with a history of hormone replacement therapy. Schuetz F, Diel IJ, Pueschel M, von Holst T, Solomayer EF, Lange S, Sinn P, Bastert G, Sohn C. Breast Unit, University Hospital Heidelberg, Heidelberg, Germany. OBJECTIVE: Substitution of estrogens (hormone replacement therapy [HRT]) is the most common therapy and prophylaxis of postmenopausal complaints. However, in most studies, long-term HRT has been associated with an increased risk for breast cancer, but the influence on a prognosis of breast cancer has been examined rarely. STUDY DESIGN: For further investigation, we analyzed 1072 patients aged 45-70 years at the time of first diagnosis of breast cancer with and without preoperative HRT with regard to the incidence of distant metastases and overall survival. Of these, 279 women were premenopausal (mean, 47.8 +/- 3.2 years); 793 women were postmenopausal (mean, 54.5 +/- 3.5 years); 320 women had received HRT over a minimum of 1 year (mean, 5.5 +/- 4.0 years; group HRT+); and 473 women had not received HRT (group HRT-). The median follow-up time was 73.2 months. RESULTS: Although body mass index, tumor size, and grading of group HRT were significantly higher than in group HRT+, nodal status, S-phase fraction, hormone-receptor status, and local recurrence showed no significant differences. In regard to the incidence of distant metastases, women without HRT have significantly (P < .001) more metastases to bone (68 vs 20 women), lung (47:13 women), and liver (47:13 women). Overall survival was significantly lower in the HRT- group. CONCLUSION: We were able to show that the use of HRT before the diagnosis of breast cancer results in more favorable primary tumors, with a lower incidence of recurrences and a better overall survival rate. This might be due to normalized bone metabolism by the use of HRT, which may lower the conditions of tumor cell seeding.