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    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. baturp@ccf.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.
                                                                                                                           
HRT After Breast Cancer?
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    Web page updated December 27, 2011
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