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Innovative Research and Patient Advocacy

HRT After Breast Cancer?

Published Evidence Contradicts Customary Advice

  • Most health care practitioners remain unaware of the published
    medical literature showing HRT- taking breast cancer patients
    actually experience equal or better survival than patients not
    taking hormones.


Study summaries 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.
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.

J Clin Oncol. 2008 Feb 4

Oral Contraceptives, Postmenopausal Hormones, and Risk of Asynchronous Bilateral Breast Cancer: The
WECARE Study Group.Figueiredo JC, Bernstein L, Capanu M, Malone KE, Lynch CF, Anton-Culver H,
Stovall M, Bertelsen L, Haile RW, Bernstein JL.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los
Angeles, CA; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New
York, NY; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA;
Department of Epidemiology, University of Iowa, Iowa City, IA; Epidemiology Division, Department of
Medicine, University of California, Irvine, CA; Department of Radiation Physics, The University of Texas M.
D. Anderson Cancer Center, Houston, TX; and the Institute of Cancer Epidemiology, Danish Cancer
Society, Copenhagen, Denmark.

PURPOSE: To investigate whether oral contraceptive (OC) use and postmenopausal hormones (PMH) are
associated with an increased risk of developing asynchronous bilateral breast cancer among women
diagnosed with breast cancer younger than 55 years. PATIENTS AND METHODS: The WECARE (Women's
Environment, Cancer, and Radiation Epidemiology) study is a population-based, multicenter, case-control
study of 708 women with asynchronous bilateral breast cancer and 1,395 women with unilateral breast
cancer. Risk factor information collected during a telephone interview focused on exposures before and
after the first breast cancer diagnosis. Treatment and tumor characteristics were abstracted from medical
records. Multivariable conditional logistic regression was used to estimate rate ratios (RR) and 95% CIs.
RESULTS: OC use before the first breast cancer diagnosis was not associated with risk of asynchronous
bilateral breast cancer (RR = 0.88; 95% CI, 0.67 to 1.16). OC use after breast cancer diagnosis was also not
significantly associated with risk (RR = 1.56; 95% CI, 0.71 to 3.45). Risk did not increase with longer
duration of use or among women who had begun using OCs at a younger age. No evidence of an
increased risk of asynchronous bilateral breast cancer was observed with PMH use before (RR = 1.21; 95%
CI, 0.90 to 1.61) or after breast cancer diagnosis (RR = 1.10; 95% CI, 0.67 to 1.77). Neither duration nor
type of PMH were associated with risk. Age at and time since first breast cancer diagnosis did not
substantially affect these results. CONCLUSION: This study provides no strong evidence that OC or PMH
use increases the risk of a second cancer in the contralateral breast.

PMID: 18250348 [PubMed - as supplied by publisher]

Related LinksOral contraceptives and breast cancer risk among younger women. [J Natl Cancer Inst. 1995]
Oral contraceptives and breast cancer risk in Taiwan, a country of low incidence of breast cancer and low
use of oral contraceptives. [Int J Cancer. 1998]Breast cancer among young U.S. women in relation to oral
contraceptive use. [J Natl Cancer Inst. 1994]Plasma sex hormone concentrations and subsequent risk of
breast cancer among women using postmenopausal hormones. [J Natl Cancer Inst. 2005]Modification of
oral contraceptive relationships on breast cancer risk by selected factors among younger women.
[Contraception. 1997]» See all Related Articles...

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

Am J Obstet Gynecol. 2007 Apr;196(4):342.e1-9.  L
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.



Hormone 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.

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 (range
3 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. Related Articles, Links
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.
agorins7@aol.com

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 cancer
recurrence, 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


1: 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. rsellin@notes.mdacc.tmc.edu

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. ncol@Dsg.harvard.edu

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.
1: Rev Med Liege. 2003 Feb;58(2):77-82. Related Articles, Links
[Hormone replacement therapy after breast cancer. Yes...or no?]

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


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