.
Scrutinizing the evidence for breast
cancer procedures and treatments
.


    W
                    Published Evidence Contradicts Medical Advice

    Most health care practitioners remain unaware that most published
    medical literature shows breast cancer patients taking HRT actually
    experienced equal or better survival than patients not taking hormones.
    See studies below from the most prestigious medical journals.
    The 26 studies below are listed in no particular order.
    





__________________________

    J Natl Cancer Inst. 2001 May 16;93(10):754-62.  

    Hormone replacement therapy after a diagnosis of breast cancer in relation to
    recurrence and mortality.  [Full Text]

    O'Meara ES, Rossing MA, Daling JR, Elmore JG, Barlow WE, Weiss NS.
    Fred Hutchinson Cancer Research Center and Department of Epidemiology, University of Washington,
    Seattle, USA.

    BACKGROUND: Hormone replacement therapy (HRT) is typically avoided for women with a history of
    breast cancer because of concerns that estrogen will stimulate recurrence. In this study, we sought to
    evaluate the impact of HRT on recurrence and mortality after a diagnosis of breast cancer. METHODS:
    Data were assembled from 2755 women aged 35-74 years who were diagnosed with incident invasive
    breast cancer while they were enrolled in a large health maintenance organization from 1977 through
    1994. Pharmacy data identified 174 users of HRT after diagnosis. Each HRT user was matched to four
    randomly selected nonusers of HRT with similar age, disease stage, and year of diagnosis. Women in the
    analysis were recurrence free at HRT initiation or the equivalent time since diagnosis. Rates of recurrence
    and death through 1996 were calculated. Adjusted relative risks were estimated by use of the Cox
    regression model. All statistical tests were two-sided. RESULTS: The rate of breast cancer recurrence
    was 17 per 1000 person-years in women who used HRT after diagnosis and 30 per 1000 person-years in
    nonusers (adjusted relative risk for users compared with nonusers = 0.50; 95% confidence interval [CI] =
    0.30 to 0.85). Breast cancer mortality rates were five per 1000 person-years in HRT users and 15 per
    1000 person-years in nonusers (adjusted relative risk = 0.34; 95% CI = 0.13 to 0.91). Total mortality rates
    were 16 per 1000 person-years in HRT users and 30 per 1000 person-years in nonusers
    (adjusted relative risk = 0.48; 95% CI = 0.29 to 0.78). The relatively low rates of
    recurrence and death were observed in women who used any type of HRT
    (oral only = 41% of HRT users; vaginal only = 43%; both oral and vaginal = 16%). No trend
    toward lower relative risks was observed with increased dose.

    CONCLUSION: We observed lower risks of recurrence and mortality in women who used HRT after breast
    cancer diagnosis than in women who did not. Although residual confounding may exist, the results suggest
    that HRT after breast cancer has no adverse impact on recurrence and mortality.
    ___________________________

    Eur J Cancer. Aug 11 2012

    Hormone replacement therapy after breast cancer: 10 year follow up of the
    Stockholm randomised trial.

    Fahlén M, Fornander T, Johansson H, Johansson U, Rutqvist LE, Wilking N, von Schoultz E.
    Department of Surgery, Capio St Görans Hospital, Stockholm, Sweden.

    BACKGROUND:

    The management of hormonal deficiency symptoms in breast cancer survivors is an unsolved problem. While
    hormone replacement therapy (HRT) may increase the risk of breast cancer in healthy women, its effects on
    recurrence is unclear. Observational studies have suggested decreased recurrence rates from HRT. The few
    clinical trials in this field have all been closed preterm.
    METHODS:
    The Stockholm trial was started in 1997 and designed to minimise the dose of progestogen in the HRT arm.
    Disease-free women with a history of breast cancer were randomised to HRT (n=188) or no HRT (n=190). The
    trial was stopped in 2003 when another Swedish study (HABITS, the Hormonal Replacement After Breast
    Cancer - Is it Safe?) reported increased recurrence. However the Stockholm material showed no excess risk
    after 4years of follow-up. A long term follow-up has now been performed.
    FINDINGS:
    After 10.8years of follow-up, there was no difference in new breast cancer events: 60 in the HRT group versus
    48 among controls (hazard ratio (HR)=1.3; 95% confidence interval (CI)=0.9-1.9). Among women on HRT, 11 had
    local recurrence and 12 distant metastases versus 15 and 12 for the controls. There were 14 contra-lateral
    breast cancers in the HRT group and four in the control group (HR=3.6; 95% CI=1.2-10.9; p=0.013).
    No differences in mortality or new primary malignancies were found.
    INTERPRETATION:
    The number of new events did not differ significantly between groups, in contrast to previous reports. The
    increased recurrence in HABITS has been attributed to higher progestogen exposure. As both trials were
    prematurely closed, data do not allow firm conclusions. Both studies found no increased mortality from breast
    cancer or other causes from HRT. Current guidelines typically consider HRT contraindicated in breast cancer
    survivors. Findings suggest that, in some women symptom relief may outweigh the potential risks of HRT.


    Climacteric. 2004 Sep;7(3):284-91Hormone replacement therapy after a diagnosis of
    breast cancer: cancer recurrence
    and mortality

    Durna EM, Wren BG, Heller GZ, Leader LR, Sjoblom P, Eden JA.
    School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.

    OBJECTIVE: To determine whether hormone replacement therapy (HRT) after treatment for breast
    cancer is associated with increased risk of recurrence and mortality. DESIGN: Retrospective
    observational study. PARTICIPANTS AND SETTING: Postmenopausal women diagnosed with breast
    cancer and treated by five Sydney doctors between 1964 and 1999. OUTCOME MEASURES: Times
    from diagnosis to cancer recurrence or new breast cancer, to death from all causes and to death from
    primary tumour were compared between women who used HRT for menopausal symptoms after
    diagnosis and those who did not. Relative risks (RRs) were determined from Cox regression analyses,
    adjusted for patient and tumour characteristics. RESULTS: 1122 women were followed up for 0-36 years
    (median, 6.08 years); 154 were lost to follow-up. 286 women used HRT for menopausal symptoms for up
    to 26 years (median, 1.75 years). Compared with non-users, HRT users had reduced risk of cancer
    recurrence (adjusted relative risk [RR], 0.62; 95% CI, 0.43-0.87), all-cause mortality (RR, 0.34; 95% CI,
    0.19-0.59) and death from primary tumour (RR, 0.40; 95% CI, 0.22-0.72). Continuous combined HRT
    was associated with a reduced risk of death from primary tumour (RR, 0.32; 95% CI, 0.12-0.88) and all-
    cause mortality (RR, 0.27; 95% CI, 0.10-0.73). CONCLUSION: HRT use for menopausal symptoms by women
    treated for primary invasive breast cancer is not associated with an increased risk of breast cancer
    recurrence or shortened life expectancy.
    ____________________________________

    Med J Aust. 2002 Oct 7;177(7):347-51.

    Hormone replacement therapy after a diagnosis of breast cancer: cancer recurrence
    and mortality.  [Full text]

    Durna EM, Wren BG, Heller GZ, Leader LR, Sjoblom P, Eden JA.
    School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.

    OBJECTIVE: To determine whether hormone replacement therapy (HRT) after treatment for breast cancer is
    associated with increased risk of recurrence and mortality. DESIGN: Retrospective observational study.
    PARTICIPANTS AND SETTING: Postmenopausal women diagnosed with breast cancer and treated by five
    Sydney doctors between 1964 and 1999. OUTCOME MEASURES: Times from diagnosis to cancer recurrence
    or new breast cancer, to death from all causes and to death from primary tumour were compared
    between women who used HRT for menopausal symptoms after diagnosis and those who did not.
    Relative risks (RRs) were determined from Cox regression analyses, adjusted for patient and tumour
    characteristics. RESULTS: 1122 women were followed up for 0-36 years (median, 6.08 years); 154 were
    lost to follow-up. 286 women used HRT for menopausal symptoms for up to 26 years (median, 1.75 years).
    Compared with non-users, HRT users had reduced risk of cancer recurrence (adjusted relative risk [RR],
    0.62; 95% CI, 0.43-0.87), all-cause mortality (RR, 0.34; 95% CI, 0.19-0.59) and death from primary tumour (RR,
    0.40; 95% CI, 0.22-0.72). Continuous combined HRT was associated with a reduced risk of death from
    primary tumour (RR, 0.32; 95% CI, 0.12-0.88) and all-cause mortality (RR, 0.27; 95% CI, 0.10-0.73).
    CONCLUSION: HRT use for menopausal symptoms by women treated for primary invasive breast cancer is
    not associated with an increased risk of breast cancer recurrence or shortened life expectancy.
    ________________________________________

    Human Reproduction 2007 22(2):616-622; doi:10.1093/humrep/del393


    Safety of hormone therapy after breast cancer: a qualitative systematic review

    C. Antoine, F. Liebens, B. Carly, A. Pastijn, S. Neusy and S. Rozenberg1
    Department of Obstetrics and Gynaecology, Free Universities of Brussels (VUB-ULB) CHU Saint-Pierre,
    Brussels, Belgium


    BACKGROUND: This qualitative review systematically analyses the safety of hormone therapy (HT) in breast
    cancer (BC) patients. METHODS: We systematically searched studies reporting the use of HT in BC patients.
    We selected 20 studies in which we evaluated the methodology, characteristics of the studied populations
    and outcomes in terms of mortality and recurrence rates (RRs). RESULTS: Many studies evaluating HT were
    uncontrolled and retrospective. Ten prospective and two randomized studies were found. These were
    characterized by heterogeneity in populations, tumour characteristics, prognostic factors and treatments.
    Two studies reported a reduced RR, and two reported lowered BC mortality rates in HT users. One
    randomized study reported an increased rate of new BC events in HT users. CONCLUSIONS: There are
    currently no reassuring data indicating the absence of a harmful effect of HT. Further studies should
    analyse whether some regimens are safer than others. There is a need for randomized trials assessing
    the safety of these regimens. In the meantime, patients should be informed about the absence of
    safety data.

    ________________________________________

    J Fam Pract. 2002 Dec;51(12):1056-62.

    Cancer recurrence and mortality in women using hormone replacement therapy: meta-
    analysis.

    Meurer LN, Lena S.

    Department of Family and Community Medicine, Medical College of Wisconsin
    OBJECTIVES: We compared the risk of cancer recurrence and all-cause mortality among users and
    nonusers of estrogen replacement therapy (ERT) after the diagnosis of breast cancer. STUDY DESIGN:
    This was a systematic review of original research. Eligible studies were reviewed by 2 investigators who
    independently extracted data from each study according to a predetermined form and assessed each
    study for validity on standard characteristics. Meta-analyses were performed with Review Manager 4.1 to
    provide a summary of relative risks of cancer recurrence and mortality. POPULATION: Studies included
    717 subjects who used hormone replacement therapy (HRT) at some time after their diagnosis of breast
    cancer, as well as 2545 subjects who did not use HRT. OUTCOMES MEASURED: Outcomes included
    breast cancer recurrence and all-cause mortality. RESULTS: Nine independent cohort studies and one 6-
    month pilot randomized controlled trial were identified. Studies were of variable quality. Breast cancer
    survivors using ERT experienced no increase in the risk of recurrence compared with controls (relative risk,
    0.72; 95% confidence interval, 0.47-1.10) and had significantly fewer deaths (3.0%) than did the nonusers
    (11.4%) over the combined study periods (relative risk, 0.18; 95% confidence interval, 0.10-
    0.31). All tests for heterogeneity were nonsignificant. CONCLUSIONS: Although limited by observational
    design, existing research does not support the universal withholding of ERT from well-informed women
    with a previous diagnosis of low-stage breast cancer. Long-term randomized controlled trials are needed.
    ___________________________

    Eur J Surg Oncol. 1999 Apr;25(2):146-51.

    A case-control study of hormone replacement therapy after primary surgical breast
    cancer treatment.

    Ursic-Vrscaj M, Bebar S. Institute of Oncology, Department of Gynecological Oncology, Ljubljana, Slovenia.

    AIMS: To investigate the presumed influence of hormone replacement therapy (HRT) on the progression
    of and death due to breast cancer. METHODS: In order to make a detailed analysis, we selected a group
    of 21 patients with the diagnosis of invasive breast cancer who had HRT after primary surgical treatment.
    Each patient from the selected group was compared with two patients from the control group with the
    diagnosis of invasive breast cancer who did not have HRT after primary surgical treatment. The control
    cases were matched to selected HRT patients with regard to age at time of the diagnosis, year of
    diagnosis, diameter of the tumour, metastatic spread in the axillary lymph nodes, and disease-free
    interval until applying HRT. The same criteria were applied in all analyses. The data were analysed by
    odds ratio (OR) calculation with a confidence interval of 95%, taking into account residual malignancy
    and death due to breast cancer in both groups (including carcinoma in the contralateral breast).
    RESULTS: HRT was applied in 21 patients treated for breast cancer. In 33% of them, radical
    mastectomy revealed metastases in the axillary lymph nodes. Hormone receptors could not be found in
    57% of patients. In the majority of patients the tumour measured 17.6mm in diameter. HRT was started
    on average 62 months (range 1-180 months) after diagnosis, and lasted an average of 28 months (range3 72
    months). All 21 patients used oestradiol as HRT, i.e. a non-conjugated oestrogen. Combined
    hormonal therapy (oestrogens + progestagens) was given to 95% of patients with median age of 47 years
    (range 41-59 years) at the beginning of HRT. Relapse was observed in four patients (19%) of the HRT group;
    of these, one had a carcinoma of the contralateral breast. In the control group, relapse was
    observed in five patients (11%); one of these five patients had a carcinoma of the contralateral breast. In
    the HRT group, there were no deaths among the patients with confirmed relapse, while one patient died
    in the control group. The estimated risk (OR= 1.74, 95%S CI 0.34-8.88) of relapse of breast cancer was
    calculated by comparing data from HRT users, who had received HRT for 28 months (range 3-72
    months) on average, with data from the control group. The estimated risk of breast cancer relapse in HRT
    users who had been receiving HRT for less than 24 months was 0.65 (OR = 0.65, 95% CI 0.02-7.85).
    CONCLUSION: Despite the inherent limitations of retrospective data and the need for prospective
    randomized trials to assess the possible influence of HRT on progression after breast cancer treatment,
    the present observations suggest that HRT treatment for less than 24 months does not appear to have a
    pronounced adverse effect on cancer outcome. Nevertheless, until appropriate clinical trials determine
    that HRT is safe, caution is needed.

    ________________________________________

    Am J Clin Oncol. 2000 Dec;23(6):541-5.

    Breast cancer survival and hormone replacement therapy: a cohort analysis.

    DiSaia PJ, Brewster WR, Ziogas A, Anton-Culver H.

    Department of Obstetrics and Gynecology, University of California Irvine Medical Center, The Chao
    Family Comprehensive Cancer Center, 92868, USA.

    Controversy exists regarding the safety of hormone replacement therapy (HRT) after a diagnosis of breast
    cancer. The objective of this study is to perform a matched cohort analysis to evaluate the impact of HRT
    on mortality in breast cancer survivors. Patients with breast cancer who received HRT after diagnosis of
    breast cancer were identified. Control subjects were identified from the regional cancer registry. Matching
    criteria included age at diagnosis, stage of breast cancer, and year of diagnosis. Controls were selected
    only if they were alive at the time of initiation of HRT of the matched case. Only subjects not included in a
    previously reported matched analysis were selected. One hundred twenty-five cases were matched with
    362 controls. Ninety-eight percent (123/125) of the cases received systemic estrogen; 90/125 (72%) also
    received a progestational agent. The median interval between diagnosis of breast cancer and initiation
    of HRT was 46 months (range 0-401 months). The median duration of HRT was 22 months (range 1-357
    months). The risk of death was lower among the HRT survivors; odds ratio 0.28 (95% confidence
    interval 0.11-0.71). This analysis does not suggest that HRT after the treatment of breast cancer is
    associated with an adverse outcome.

    _______________________________

    J Clin Oncol. 1999 Jan;17(1):130-42.

    Elements of informed consent for hormone replacement therapy in patients with
    diagnosed breast cancer.

    Chlebowski RT, McTiernan A. University of California Los Angeles School of Medicine, Harbor-UCLA, Medical
    Center

    PURPOSE: An approach to providing informed consent to breast cancer survivors considering hormone
    replacement therapy (HRT) is offered. METHODS: Current information on HRT, breast cancer, and
    chronic disease prevention is reviewed in the context of risks faced by women with resected breast
    cancer. RESULTS: Breast cancer patients, unwilling to trade symptom reduction for even a small
    increase in recurrence risk, are at substantially increased risk of death from breast cancer relative to
    other causes. Observational studies suggest that long-term HRT increases breast cancer development.
    The influence of HRT on the growth of established breast cancer has not been determined; however,
    estrogen reduction (oophorectomy) significantly reduces recurrence in premenopausal women, and current
    evidence cannot exclude a risk that HRT increases recurrence to the same degree. The following issues
    are of particular relevance to breast cancer survivors: HRT reduces mammographic sensitivity, increases
    thromboembolic events, and increases endometrial cancer risk. Although benefit for HRT is commonly
    inferred from observational studies, randomized trials of HRT on all-cause mortality have not been
    completed. For coronary heart disease prevention, an array of strategies independent of HRT are
    available, with some (tamoxifen, selective estrogen receptor modifiers [SERMs], diet, and exercise) likely
    to favorably influence breast cancer risk; for osteoporosis prevention, an array of strategies also are
    available, with some (bisphosphonates, tamoxifen, SERMs, and exercise) likely to favorably influence
    breast cancer risk. CONCLUSION: Current data preclude the generation of evidence-based guidelines for
    HRT use in breast cancer survivors, and clinical trials in this setting should be supported. However, given
    available therapeutic alternatives for menopausal symptom management and chronic disease prevention,
    breast cancer survivors should be offered HRT only with caution and with their full participation in the
    decision-making process.

    _____________________________

    Am J Surg. 1993 Mar;165(3):372-5.

    Hormone replacement therapy in previously treated breast cancer patients.

    Wile AG, Opfell RW, Margileth DA.  Department of Surgery, UC Irvine 92668.

    We report our experience with 25 women previously treated for breast cancer who subsequently received
    hormone replacement therapy (HRT) for the relief of menopausal symptoms and the prevention of
    postmenopausal cardiovascular disease and osteoporosis. Two patients had in situ disease, 13 had
    stage I disease, 7 had stage II disease, 1 had stage III disease, and 2 had invasive cancer of
    undetermined stage. Seventeen patients (group I) began HRT less than 24 months after primary breast
    cancer therapy, and 8 patients (group II) began HRT more than 24 months after breast cancer therapy.
    The HRT-free interval for group I patients averaged 7.9 months and for group II patients averaged 64.5
    months. The average period of observation while receiving HRT for the entire group was 35.2 months
    (range: 24 to 82 months). Three of 25 patients have had a recurrence, all in group I. One patient
    developed local recurrence after breast conservation treatment, and her condition was salvaged by further
    wide excision. Two patients developed recurrence after mastectomy, and one patient ultimately died of
    systemic disease. The overall survival rate for the entire group was 96%. Overall survival of high-risk
    group I patients, with a mean follow-up of 30.4 months, was 94%. We recognize that this report of HRT in
    a small group of patients does not have the power to demonstrate an adverse effect of HRT on breast
    cancer. However, the lack of an obvious adverse effect of HRT in this group of breast cancer patients
    and the known beneficial effect of HRT on postmenopausal cardiovascular disease and osteoporosis
    warrant formal prospective trials of HRT in such patients.
    ___________________________

    Gynecol Obstet Fertil. 2003 Jul-Aug;31(7-8):614-9.

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

    Gorins A, Espie M, Bedairia N, Perret F, Tournant B, Novak H, Lucchi-Angelier E, Marty M.
    Centre des maladies du sein, hopital Saint-Louis, 1, avenue Claude-Vellefaux, 7574, Paris, France.

    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.

    ___________________________
    Hormone replacement therapy in breast cancer survivors: the Israeli Society for Clinical
    Oncology and Radiotherapy policy letter] [Article in Hebrew]

    Siegelmann-Danieli N, Ron I, Kaufman B, Uzieli B, Karminsky N, Inbar M; Israeli Society for Clinical
    Oncology and Radiotherapy. Assaf Harofeh Medical Center, Zerifin.

    The Israeli Society for Clinical Oncology and Radiotherapy requested that experts in breast cancer
    therapy assess the Society's policy regarding the use of hormone replacement therapy (HRT) in breast
    cancer survivors. The following recommendations are based on updated literature, which is limited since
    it summarizes only retrospective data. There is currently no evidence of an increased risk of breast
    cancerrecurrence, death attributable to cancer, or overall mortality among breast cancer survivors who
    use HRT. We therefore recommend that there is no need to avoid HRT in women with menopausal
    symptoms who are interested in receiving such treatment, as long as ovarian ablation does not play
    a major role in their adjuvant therapy. Women should be informed about the limitations of available data.
    There are some concerns regarding the use of HRT in patients whose tumors developed while undergoing
    HRT and in such cases treatment should be reserved only for those with severe menopausal symptoms.
    For women with milder symptoms or those who are not interested in HRT, other treatment options should
    be outlined. The policy should be updated according to future publication of results from ongoing
    randomized prospective studies.

    ___________________________
    Oncology. 2001;60(3):199-206.

    Hormone replacement therapy after treatment of breast cancer: effects on
    postmenopausal symptoms, bone mineral density and recurrence rates.

    Beckmann MW, Jap D, Djahansouzi S, Nestle-Kramling C, Kuschel B, Dall P, Brumm C, Bender HG.
    Department of Obstetrics and Gynecology, Friedrich Alexander University, Erlangen, Germany.

    PURPOSE: Breast cancer (BC) is the most frequent female carcinoma and the major cause of death in
    women aged 35--50 years. The total number of patients surviving BC and especially the morbidity rate of
    patients below the age of 55 years has increased significantly in the last several years. As a
    consequence, the number of BC patients suffering from the long-term effects of estrogen deficiency due
    to adjuvant treatment is increasing. At present, hormone replacement therapy (HRT) following BC
    treatment is applied individually and mainly depends on the severity of postmenopausal symptoms (PMS)
    experienced by these patients. PATIENTS AND METHODS: In a retrospective study (total n = 185 BC
    patients, 64 with and 121 without HRT), the effect of HRT during or after adjuvant therapy [chemotherapy
    and/ or (anti-) hormonotherapy] has been investigated. The surveillance period was up to 60 months.
    Evaluated were HRT effects on (1) PMS measured by a comprehensive life quality questionnaire, (2)
    bone mineral density (BMD) measured by osteodensitometry and (3) morbidity as well as mortality rates.
    RESULTS: Both groups did not differ with regard to tumor stage, lymph node involvement, metastasis,
    grading, and steroid hormone receptor status. A reduction in PMS was significant in women taking HRT
    (p < 0.001), especially in the subgroup of women < or =50 years (p < 0.0001). For both age groups, the
    median reduction in BMD (z-score) was less in women receiving HRT (< or =50 years: without HRT -1.99
    vs. with HRT -0.95, p < 0.05; >50 years: without HRT -2.29 vs. with HRT -1.19, p < 0.01). There were no
    statistically significant differences regarding morbidity and mortality (p = 0.29). CONCLUSION: In this
    study of BC patients, the use of HRT shows positive effects on PMS and BMD. There was no significant
    influence on morbidity or mortality. However, a reevaluation of HRT in the routine management of BC
    patients should await the results of prospective randomized trials. Copyright 2001 S. Karger AG, Basel
    ___________________________
    J Clin Oncol. 1999 May;17(5):1482-7.

    Estrogen replacement therapy after localized breast cancer: clinical outcome of 319
    women followed prospectively.

    Vassilopoulou-Sellin R, Asmar L, Hortobagyi GN, Klein MJ, McNeese M, Singletary SE, Theriault RL.
    Department of Breast and Gynecologic Medical Oncology, M.D. Anderson Cancer Center, University of
    Texas, Houston 77030, USA.

    PURPOSE: To determine whether estrogen replacement therapy (ERT) alters the development of new or
    recurrent breast cancer in women previously treated for localized breast cancer. PATIENTS AND
    METHODS: Potential participants (n = 319) in a trial of ERT after breast cancer were observed
    prospectively for at least 2 years whether they enrolled onto the randomized trial or not. Of 319 women,
    39 were given estrogen and 280 were not given hormones. Tumor size, number of lymph nodes,
    estrogen receptors, menopausal status at diagnosis, and disease-free interval at the initiation of the
    observation period were comparable for the trial participants (n = 62) versus nonparticipants (n = 257)
    and for women on ERT (n = 39) versus controls (n = 280). Cancer events were ascertained for both
    groups. RESULTS: Patient and disease characteristics were comparable for the trial participants versus
    nonparticipants, as well as for the women on ERT versus the controls. One patient in the ERT group
    developed a new lobular estrogen receptor-positive breast cancer 72 months after the diagnosis of a
    ductal estrogen receptor-negative breast cancer and 27 months after initiation of ERT. In the control
    group, there were 20 cancer events: 14 patients developed new or recurrent breast cancer at a median
    time of 139.5 months after diagnosis and six patients developed other cancers at a median time of 122
    months. CONCLUSION: ERT does not seem to increase breast cancer events in this subset of patients
    previously treated for localized breast cancer. Results of randomized trials are needed before any changes
    in current standards of care can be proposed.
    ___________________________

    Am J Obstet Gynecol. 1996 May;174(5):1494-8.

    Hormone replacement therapy in breast cancer survivors: a cohort study.

    DiSaia PJ, Grosen EA, Kurosaki T, Gildea M, Cowan B, Anton-Culver H.
    Department of Obstetrics and Gynecology, University of California, Irvine Medical Center, Orange, CA
    92668, USA.

    OBJECTIVE: Our purpose was to measure any adverse effect (if one exists) of hormone replacement
    therapy administered to breast cancer survivors. STUDY DESIGN: Forty-one patients from a group of 77
    patients who received hormone replacement therapy after therapy for breast cancer were matched with
    82 comparison patients not receiving hormone replacement therapy. Both groups were taken from the
    same population on the basis of cancer registry of the Cancer Surveillance Program of Orange County
    and were compared with regard to survival results. RESULTS: An analysis of survival time and disease-free
    time revealed no statistically significant difference between the two groups. CONCLUSIONS: No obvious
    adverse effect of hormone replacement therapy could be shown in this pilot study. A case is made for a
    prospective randomized trial.
    __________________________


    J Clin Oncol. 2001 Apr 15;19(8):2357-63.

    Hormone replacement therapy after breast cancer: a systematic review and quantitative
    assessment of risk.

    Col NF, Hirota LK, Orr RK, Erban JK, Wong JB, Lau J.
    Division of General Medicine and Decision Systems Group, Brigham and Women's Hospital and Harvard
    Medical School, Chestnut Hill, MA 02467, USA.

    PURPOSE: Hormone replacement therapy (HRT) is typically withheld from women with breast cancer
    because of concern that it might increase the risk of recurrence. The purpose of this study was to quantify
    the risk of recurrent breast cancer associated with HRT among breast cancer survivors. METHODS: We
    performed a systematic literature review through May 1999, calculating the relative risk (RR) of breast
    cancer recurrence in each study by comparing the number of recurrences in the HRT group to those in
    the control group. In studies that did not contain a control group, we constructed one by estimating the
    expected number of recurrences based on data from the Early Breast Cancer Trialists' Collaborative
    Group, adjusting for nodal status and disease-free interval. RRs across all studies were combined using
    random-effects models. RESULTS: Of the 11 eligible studies, four had control groups and included 214
    breast cancer survivors who began HRT after a mean disease-free interval of 52 months. Over a mean
    follow-up of 30 months, 17 of 214 HRT users experienced recurrence (4.2% per year), compared with 66
    of 623 controls (5.4% per year). HRT did not seem to affect breast cancer recurrence risk (RR = 0.64,
    95% confidence interval [CI], 0.36 to 1.15). Including all 11 studies in the analyses (669 HRT users),
    using estimated control groups for the seven uncontrolled trials, the combined RR was 0.82 (95% CI,
    0.58 to 1.15). CONCLUSION: Although our analyses suggest that HRT has no significant effect on breast
    cancer recurrence, these findings were based on observational data subject to a variety of biases.
    ___________________________

    Am J Obstet Gynecol. 1999 Aug;181(2):288-95.

    Estrogen replacement therapy in women with previous breast cancer.

    Natrajan PK, Soumakis K, Gambrell RD Jr.
    Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA.

    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.
    ___________________________

    Am J Obstet Gynecol. 2002 Aug;187(2):289-94; discussion 294-5.

    Estrogen replacement therapy in patients with early breast cancer
    .
    Natrajan PK, Gambrell RD Jr.
    Reproductive Endocrinologists, Augusta, GA 30910, USA.

    OBJECTIVE: Most physicians believe that estrogen replacement therapy is contraindicated once a
    patient is diagnosed with breast cancer. Recently, several studies have shown that estrogen replacement
    therapy may be safely used in patients with early breast cancer that has been treated successfully. These
    women can have severe menopausal symptoms and are at risk for osteoporosis. We reviewed the current
    status of women in our practice with breast cancer who received estrogen replacement therapy, who did
    not receive hormone replacement therapy, and who did not receive estrogenic hormone replacement
    therapy. STUDY DESIGN: The study group consisted of 123 women (mean age, 65.4 +/- 8.85 years)
    who were diagnosed with breast cancer in our practice, including 69 patients who received estrogen
    replacement therapy for < or = 32 years after diagnosis. The comparative groups were 22 women who
    used nonestrogenic hormones for < or = 18 years and 32 women who used no hormones for < or = 12
    years. The group who did not receive estrogenic hormone replacement therapy received androgens with
    or without progestogens (such as megestrol acetate). Of the 63 living hormone users, 56 women are still
    being treated in our clinic, as are 15 of the 22 subjects who receive nonestrogenic hormone replacement
    therapy. Follow-up was done through the tumor registry at University Hospital; those patients whose
    tumor records were not current were contacted by telephone. RESULTS: There were 18 deaths in the
    123 patients: 6 patients who received estrogen replacement therapy (8.69%), 2 patients who received
    nonestrogenic hormone replacement therapy (9.09%), and 10 patients who received no hormone
    replacement therapy (31.25%). Of the 18 deaths, 9 deaths were from breast cancer (mortality rate,
    7.3%); 3 deaths were from lung cancer; 1 death was from endometrial cancer; 1 death was from
    myocardial infarction; 1 death was from renal failure; and 3 deaths were from cerebrovascular accidents.
    The 9 deaths from breast cancer included one patient who received nonestrogenic hormone replacement
    therapy (mortality rate, 4.5%), 6 patients who received no hormone replacement therapy (mortality rate,
    11.3%), and 2 patients who received estrogen replacement therapy (mortality rate, 4.28%). The 9 non-
    breast cancer deaths included 4 patients who received estrogen replacement therapy (endometrial
    cancer [1 death], lung cancer [1 death], cerebrovascular accident [1 death], and renal failure [1 death]), 1
    patient who did not receive estrogenic hormone replacement therapy group (myocardial infarction), and 4
    patients who used no hormones (lung cancer, 2 deaths; stroke, 2 deaths). Carcinoma developed in one
    patient in the estrogen replacement therapy group in the contralateral breast after 4 years of hormone
    replacement therapy; she is living and well 2.5 years later with no evidence of disease. Metastatic breast
    cancer developed in one patient after 8 years of hormone replacement therapy; she is living with disease.
    CONCLUSION: Estrogen replacement therapy apparently does not increase either the risk of recurrence
    or of death in patients with early breast cancer. These patients may be offered estrogen replacement
    therapy after a full explanation of the benefits, risks, and controversies.
    ___________________________

    Rev Med Liege. 2003 Feb;58(2):77-82.

    Hormone replacement therapy after breast cancer. Yes...or no?
    [Article in French]

    Foidart JM, Desreux J, Lifrange E, Colin C.
    Departement de Gynecologie-Obstetrique-Senologie, CHU de Liege.

    Clinical and experimental studies indicate that combined unique conjugated estrogens and
    medroxyprogesterone acetate moderately increase the risk of breast cancer in postmenopausal women.
    Classically, hormone replacement therapy is contra-indicated in women with a past history of breast
    cancer due to the fear of recurrence. However, these postmenopausal patients complain about hot
    flushes and adjuvant hormonal therapies (such as aromatase inhibitors, SERMs and Tamoxifen...)
    aggravate their symptoms. Observational studies and their meta-analyses do not show a deleterious effect
    but rather a beneficial impact of hormone replacement therapy among women with a past history of breast
    cancer. We summarise all these studies and their biological, clinical and epidemiological interpretations.
    We conclude that short term hormone replacement therapy is safe among those women requesting a
    replacement therapy after complete information. It is however advisable to conclude definitely only when
    prospective randomised trials with estradiol or tibolone (a promising alternative) will be available. Such
    ongoing studies will allow to conclude definitely the possible benefits and risks of hormone replacement
    therapy among patients with a past history of breast cancer.
    __________________________
    Int J Gynaecol Obstet. 1999 Jan;64(1):59-63.

    Estrogen replacement therapy in breast cancer survivors.

    Guidozzi F. Department of Obstetrics and Gynaecology, Johannesburg Hospital, University of the
    Witwatersrand Medical School, South Africa.

    OBJECTIVE: To determine whether estrogen replacement therapy (ERT) adversely affected outcome of
    breast cancer survivors. METHOD: A prospective descriptive study of all breast cancer survivors who
    requested ERT because of intractable menopausal symptoms. All patients presented voluntarily as
    gynecological outpatients and were all given oral continuous opposed ERT: 20 premarin and
    medroxyprogesterone and four tibolone. RESULTS: Twenty-four patients who had previously been
    treated for breast cancer 8-91 months prior to their initiating ERT have been observed for 24-44 months.
    There were 15 patients with stage 1, eight with stage 2 and one with stage 4 breast cancer. The mean
    age of the patients at commencement of ERT was 48 years (range 42-61). Two patients had a biopsy of a
    suspicious breast nodule: both of which were benign. There have not been any recurrences to date.
    CONCLUSION: Breast cancer survivors did not have their outcome adversely affected by ERT during an
    observation period of 24-44 months

HRT After Breast Cancer:

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