Luteal phase defect and breast cancer genesis

Abstract

SummaryThe possibility that an unopposed estrogen effect mainly due to a progesterone secretion insufficiency of the corpus luteum might be involved in the promotion of human breast cancer remains a challenging hypothesis (Sherman et al.: Breast Cancer Res Treat 1: [287][288][289][290][291][292][293][294][295] 1981). This review based upon recent data is another approach to this problem, attempting to provide a pathophysiological interpretation of breast cancer risk in terms of luteal phase insufficiency.

Early Menarche, a Risk Factor for Breast Cancer, Indicates Early Onset of Ovulatory Cycles*

“…Our findings are therefore in direct conflict with the hypotheses suggesting that a long duration of exposure to anovulatory cycles or to cycles with an inadequate luteal phase is associated with an increased risk of breast cancer in women with early menarche (3)(4)(5). The most salient finding was that in the group with earliest menarche ovulatory cycles (serum progesterone more than 6.4 nmol/liter) were established earlier in relation to time since menarche and even more so in relation to chronological age.…”

“…Other theories should therefore be considered, among them the following: 1) high serum progesterone concentration in association with normal or high serum estradiol at puberty increases the risk, 2) only the early and relatively high estrogen concentrations are important, or 3) the estrogen to androgen ratio is the critical factor, with androgens having a protective effect. It has been postulated that normal estrogen stimulation in association with luteal inadequacy could explain the increased risk associated with early menarche (3)(4)(5). The relative risk is 2-fold at young ages for women with menarche before 12 yr of age compared with menarche at 13 yr or more (2).…”

Antiestrogen Action of Progesterone in Breast Tissue

“…They are in agreement with the hy pothesis of a protective effect of progester one or progestins against the mitogenic ac tivity of estrogens in breast target tissue [ 1,2], Inversely, the fact that the progestin R 5020 inhibits breast cell multiplication may be opposed to the recent speculations of Pike et al [3,4] on the role of progestins con tained in oral contraceptive preparations as factors increasing breast cell division. Whereas progestins actually inhibit breast cell division, the efficiency with which phys iologic concentrations of progesterone coun teract the mitogenic effect of estrogens is not as well documented.…”

“…These controversies are re lated to the possibility that an unopposed estrogen effect due to a defect in progester one secretion during the luteal phase might be a promoting factor in human breast can cer genesis [1,2]. The fact that this hypothe sis remains controversial is due to the insuf ficient knowledge on the antiestrogenic ac tivity of progesterone and progestins in hu man breast cells.…”

“…Many controversies have arisen recently in the literature about progesterone action in the breast [1][2][3][4]. These controversies are re lated to the possibility that an unopposed estrogen effect due to a defect in progester one secretion during the luteal phase might be a promoting factor in human breast can cer genesis [1,2].…”