Correspondence to: Naira S. Chobanyan, M.D., Ph.D., D.Sc., 7/2 Proshian St., 375019 Yerevan, Armenia.
I have studied with great interest the report by Hankinson et al. (1). Using a case-control study nested within the Nurses' Health Study, these authors prospectively evaluated the relationship between levels of sex steroid hormones in plasma and the risk of breast cancer in postmenopausal women. They observed statistically significant positive associations between breast cancer risk and circulatory levels of estradiol, estrone sulfate, and dehydroepiandrosterone. At the same time, they found no substantial association with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The data obtained by Hankinson et al. provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer and also suggest ". . . that increased levels of testosterone may have a modest, but indirect, association with breast cancer through its conversion to estradiol" (1).
Hankinson et al. have cited some papers concerning the relationship between breast cancer risk and testosterone level in the serum of postmenopausal women [references (10-12,46-51) cited in their report (1)]. Three papers [references (50,51) cited in reference (1) as well as the report by Hankinson et al. (1)] have shown no positive association between testosterone level and risk of breast cancer, but another seven papers [references (10-12,46-49) cited in reference (1)] and the work of Dorgan et al. (2) support the hypothesis that the concentration of testosterone in serum is related to the subsequent diagnosis of breast cancer in postmenopausal women. Thus, the data are contradictory and inconclusive. Less is known about the relationship between the serum concentration of testosterone and the risk of breast cancer in premenopausal women. I could find only one study (3) with results that favored a role for increased androgenic activity in breast cancer.
In this letter, I will present some results that were obtained in cooperation with scientists from the Cancer Research Center in Moscow (Russia). These results were published in Russian and are possibly not available for Western readers (4,5). We studied a total of 1232 premenopausal patients with breast cancer; 637 patients were less than 35 years old ("young" patients) and 595 patients were 36-45 years old ("middle-aged" patients). Overall survival of the young patients was statistically significantly lower than that of the "middle-aged" group (P<.05) (4). We also studied sex hormone levels in the serum of 60 of the young patients with breast cancer and 50 healthy control women of corresponding young age as well as in the serum of 60 of the middle-aged patients with breast cancer and 50 healthy control women of corresponding middle age (5,6). We showed that the steroid hormone concentration in serum depended on the phase of the menstrual cycle and that the basal level of secretion of 17ß-estradiol was similar in young patients, middle-aged patients, and the control groups. In the follicular phase of the menstrual cycle, the level of testosterone in the young patients was statistically significantly (P<.05) higher than that in both control groups and in the middle-aged patients (4-6); in the luteal phase of the menstrual cycle, the level of testosterone in the young patients was increased only in comparison with that in the corresponding young control group (4-6). In contrast, in the middle-aged patients, in the follicular and ovular phases, the level of testosterone was decreased compared with that in the corresponding middle-aged control group. The concentration of sex hormone-binding globulin (4) in the serum of young patients did not depend on the phase of the menstrual cycle and was higher than that in the serum of the corresponding young control group; the level of sex hormone-binding globulin was similar in middle-aged patients and in the corresponding middle-aged control group.
Our results for estradiol, its free fraction, and sex hormone-binding globulin concentration in serum supported those obtained by Grattarola (7), who found that breast cancer in young patients was estrogen independent and associated with hyperandrogenia, which plays an important role in the development of metastatic breast cancer disease.
In conclusion, the data concerning the relationship between risk of breast cancer in premenopausal and postmenopausal women and concentrations of androgens are contradictory, but results of the most recent investigations have shown that such a relationship exists. In my opinion, this problem is not solved and warrants further investigations.
REFERENCES
1
Hankinson SE, Willett WC, Manson JE, Colditz GA, Hunter DJ,
Spiegelman D, et al. Plasma sex steroid hormone levels and risk of breast cancer in
postmenopausal women. J Natl Cancer Inst 1998;90:1292-9.
2 Dorgan JF, Longcope C, Stephenson HE Jr, Falk RT, Miller R, Franz C, et al. Serum sex hormone levels are related to breast cancer risk in postmenopausal women. Environ Health Perspect 1997;105 Suppl 3:583-5.[Medline]
3 Secreto G, Toniolo P, Pisani P, Recchione C, Cavalleri A, Fariselli G, et al. Androgens and breast cancer in premenopausal women. Cancer Res 1989;49:471-6.[Abstract]
4 Chobanian NS. Breast cancer in young women [abstract of dissertation]. Moscow (Russia): Edition of the All-Union Cancer Research Center of the USSR Academy of Medical Sciences; 1992.
5 Chobanian NS, Kushlinskii NE, Bassalyk LS, Kuz'mina ZV, Savel'ieva EV, Baryshnikov AIu, et al. Estradiol-17beta, sex steroid-binding globulin and cellular and humoral immunity indices in young women with breast cancer. Vopr Onkol 1992;38:439-46.[Medline]
6 Chobanyan NS, Kushlinsky NE. Interrelationship between cellular and humoral immunity indices and pituitary hormone levels in the blood of young patients with breast cancer [abstract]. Eur J Cancer 1993;29A:S61.
7 Grattarola R. Androgens in breast cancer. I. Atypical endometrial hyperplasia and breast cancer in married premenopausal women. Am J Obstet Gynecol 1973;116:423-8.[Medline]
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