Hormone Therapy Possibilities for Breast Cancer Survivors and
Women at High Risk for Cancer
by Pete Hueseman RPh, PharmD
brought to you by Bellevue Pharmacy, a ProjectAWARE
Past History of Breast Cancer
Patients with past history of breast cancer should not have estradiol
or estrone recommended for estrogen supplementation. These estrogens
play a role in causing breast cancer by damaging DNA. Estriol is
the protective estrogen that is high during pregnancy. It does not
activate the estrogen receptor, but occupies the receptor sites
so that it is not available for estradiol. Hormone balance is important,
and testing of hormone levels is recommended prior to supplementing.
For post breast cancer patients, many medical practitioners do not
recommend hormone supplementation, except for progesterone, unless
hormone levels are well below normal and symptoms are severe. Use
of hormones should be carefully tracked by both patient and doctor.
Here's what we suggest:
- Estriol should be recommended (2 mg twice
a day) and is thought to reduce the risk of breast cancer recurrence.
For atrophy of vaginal tissues and urethral problems in post breast
cancer patients, a compounded estriol cream (.5 mg/gram applied
topically 2 - 3 times a week) is considered safe.
- Progesterone has the effect of down regulation
of estrogen receptors in breast and uterine tissue.
- Testosterone has been reported in some studies
to have an anti-carcinogenic effect on breast cancer cells and
in clinical studies has demonstrated increased survival rates
for patients receiving testosterone vs. those who did not.
- Arimidex prevents aromatization of testosterone to estradiol
and aromatization of androstenedione to estrone. The ATAC study
has documented Arimidex as better than tamoxifen or placebo for
early-stage, hormone-receptor-positive breast cancer. The early
ATAC results do suggest that Arimidex might have benefits over
tamoxifen, but the decision to start taking Arimidex instead of
tamoxifen is not clear-cut at this point.
Two things we know about Arimidex:
- Arimidex and tamoxifen should not be taken together.
There appears to be no proven advantage to the combination
over tamoxifen or Arimidex alone, and you may have side
effects from both drugs.
- Aromatase inhibitors have no proven role in pre-menopausal
women diagnosed with breast cancer.
- Indole-3-Carbinol prevents conversion of 2-hydroxyestrone to
the carcinogenic 16-hydroxyestrone and 4-hydroxyestrone.
Drug therapy recommendations:
- Estriol 2.5 mg + Progesterone 100 mg + Testosterone 1.25 mg.
Take one sublingual tablet twice a day.
- Arimidex (anastazole) 1 mg tablets. Take one everyday.
- Indole-3-carbinol 400 mg. Take one capsule daily.
Certainly a person with an estrogen-receptor-positive tumor is
at much higher risk with estradiol treatment than an estrogen-receptor-negative
tumor. However, both types of tumors have an elevated risk of recurrence
with estradiol treatment.
My thoughts are that a patient with a history of estrogen-receptor-positive
tumor should DEFINITELY be on Arimidex for life! She also should
not receive estradiol, of course. The other hormones (except DHEA)
are fine. The downside for women at risk of breast cancer is that
DHEA can convert to estrogen and has a stimulatory effect on breast
cells, particularly when estrogen is low. Close watch on overall
hormone balance levels is required, and testing is recommended every
6 months. In terms of estrogen receptor negative, I would say that
Arimidex is probably not a must.
High Risk for Breast Cancer
A patient with a high risk (based on the Gail Model) for breast
cancer would benefit from supplementation of estrogen and progesterone
with human identical hormones in ratios similar to those in the
Progesterone is recommended for benefits of fluid balance and
protection against cancer. Progesterone has the effect of down regulation
of estrogen receptors in the breast.
Patients are also likely to benefit from estriol with its potential
for protection against breast cancer recurrence due to its low estrogenic
activity, which possibly results in binding to estrogen receptors
without stimulation of receptor. This is recommended in a higher
ratio of estriol to estradiol than the typical ratio seen in Biest
(80%/20%). For patients with a higher risk for breast cancer, we
recommend 90%/10% estriol/estradiol.
We also recommend Indole-3-Carbinol to prevent conversion of 2-hydroxyestrone
to the carcinogenic 16-hydroxyestrone and 4-hydroxyestrone. This
will provide additional protection against breast cancer and should
be considered in the patient with positive family history.
Drug Therapy Recommendations:
- 90% estriol/10% estradiol sublingual tablet. Take one under
the tongue twice a day.
- Progesterone 100 mg sublingual tablets. Take one under the
tongue twice a day.
- Indole-3 Carbinol (Cervaplexx I3-C) 400 mg. Take one every
In response to the book "The Sexy Years" by Suzanne
Somers, we have not found in the last 12 years any significant increase
in insulin resistance with continuous therapy. I do not feel it
is necessary to cycle therapy if you have been in post-menopause
for over one year.
Lastly, in most instances it will be rather difficult for patients
to find an endocrinologist in their area to work with them and natural
hormone therapy. My suggestion for women would be to use your regular
OB-GYN and contact us if the patient needs assistance.
- Hoover R. Gray LA Cole P. et al: Menopausal estrogens and breast
cancer. N Engl J Med 295:401-405, 1976.
- Smith LH, Gordon GS Medical staff conference: Postmenopausal
osteoporosis. West J Med 125:137-142, 1976.
- Halberstam MJ: If estrogens retard osteoporosis, are they worth
the cancer risk? Mod Med 45:9, 15, 1977.
- Speroff L: The breast as an endocrine target organ.Contemp Obstet
Gynec 9:69-72, 1977.
- Gold JJ: Figure 5-7 in Gold JJ (ed). Gynecologic Endocrinology,
ed 2. New York. Harper & Row Publishers Inc. 1975, p.67.
- Ryan KJ: Biosynthesis of ovarian steroids, in Danforth DN (ed):
Textbook of Obstetrics and Gynecology, ed 2. New York. Harper
& Row Publishers Inc. 1971, pp131-134.
- Yen SSC, Martin PL, Burnier NM, et al: Circulating estradiol,
estrone and gonadotropin levels following the administration of
orally active 17 b-estradiol in postmenopausal women. J Clin Endocrinol
Metab 40:518-521, 1975.
- Thijssen JHH, Poortman J, Schwarz F, et al: Post-menopausal
estrogen production with special reference to patients with mammary
carcinoma. Front Horm Res 3:45-62, 1975.
- Lauritzen C: The female climacteric syndrome: Significance,
problems, treatment, Acta Obstet Gynecol Scand 51 (suppl): 49-61,
- Lauritzen C: The management of the pre-menopausal and the post
menopausal patient. Front Horm Res 2: 2-21, 1973.
- Bulbrook P.D, Swain MC, Wang DY, et al: Breast cancer in Britain
and Japan: Plasma oestradiol-17b, oestrone and progesterone and
their urinary metabolites in normal British and Japanese women.
Eur J Cancer 12:725-735, 1976.
- breastcancer.org - A non-profit organization for breast cancer
education discusses Arimidex (ATAC Trial). http://www.breastcancer.org/research_hormonal_120001a.html
- AstraZeneca Oncology - Breast Cancer Healthcare Professional
summarizes the Arimdex (anastrozole); ATAC Trial http://www.breastcancerprofessionalinfo.com/atac-study.htm
- Medscape: ATAC trial: Aromatase Inhibitors in the Adjuvant
Setting: Available Data. http://www.medscape.com/viewarticle/424077_5
- Lemon HM: Estriol prevention of mammary carcinoma induced by
7, 12-dimethylbenzanthracene and procarbazine, Cancer Res 35:1341-1353,
- Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer
C, Mulvihill JJ. Projecting individualized probabilities of developing
breast cancer for white females who are being examined annually.
J Natl Cancer Inst 1989;81:1879-1886.
- Costantino JP, Gail MH, Pee D, Anderson S, Redmond CK, Benichou
J, Wieand HS. Validation studies for models projecting the risk
of invasive and total breast cancer incidence. J Natl Cancer Inst
- Indole-3-carbinol(13c) and Dindolylmethane (DIM) abstracts:
For questions and further information, contact