HRT After Breast Cancer

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HRT after Breast Cancer Part 2

Study summaries continued:

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.

Publication Types:
· Clinical Trial

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.
mlevgur@maimonides.org

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

PMID: 15305822 [PubMed - in process]

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. george.peters@utsouthwestern.edu

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.
ddecker@beaumont.edu

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.

PMID: 12851510 [PubMed - indexed for MEDLINE

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