Hormone dependence in breast cancer

McGuire, William; Chamness, Gary C.; Costlow, Mark E.; Shepherd, Roger E.

doi:10.1016/0026-0495(74)90106-1

Cited by 78 publications

(25 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although this phenomenon has been previously reported and is not unique to the Lewis strain rat, it has received little attention and has not been adequately studied (8,15,30,31). The regressed site (state) of these tumors can be readily identified and does not appear to differ histologically from the regressed condition of ODTs.…”

Section: Methodsmentioning

confidence: 95%

See 1 more Smart Citation

Histopathogenesis of 7,12-diemthylbenz(a)anthracene-induced rat mammary tumors.

Haslam

Bern

1977

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The histopathogenesis and growth behavior of mammary tumors and dysplasias induced by a single intragastric dose of 7,12-dimethylbenz[ajanthracene in 50-day-old virgin female Lewis rats were examined both in situ and after transplantation into gland-free mammary fat pads of syngeneic hosts. Terminal mammary ductules are indicated as a site of origin of both ovarian hormone-dependent mammary tumors and spontaneously regressing mammary tumors, and terminal ductule hyperplasia appears to be an early stage in mammary tumor formation. The precancerous nature of hyperplastic alveolar nodules induced by dimethylbenzanthracene in rats has been further examined, and our studies indicate that these nodules are not significantly preneoplastic.Several studies indicate that the site of origin of human mammary carcinoma may be in lobules and terminal ductules of the mammary gland (1-6). It is known that in 30-40% of individuals mammary cancer is hormone responsive, whereas in the remainder it is not (7-9). At present it is not known if the histopathogenesis of these two forms of mammary cancer differ. For many reasons such studies are difficult to undertake in human beings, but the problem can be approached by using a suitable animal model. When 7,12-dimethylbenz[a ]anthracene (DMBA) is administered to the rat, numerous mammary gland dysplasias and mammary carcinomas occur (10-13). It has been reported that approximately 80% of the tumors arising are ovarian hormone-dependent (14,15). Rat mammary carcinomas are claimed to arise in small mammary ducts (16)(17)(18) or from hyperplastic alveolar nodules (19,20). The work presented here was undertaken to describe the histopathogenesis of rat DMBA-induced ovary-dependent tumors and ovary-independent mammary tumors in order to identify their site(s) of origin and to reexamine the preneoplastic nature of DMBAinduced mammary gland dysplasias. MATERIALS AND METHODSInbred virgin female Lewis strain rats (Simonsen Laboratory, Gilroy, CA) at 50 days of age were fed DMBA (Sigma) intragastrically at 0.015 g/100 g of body weight, dissolved in 1 ml of sesame oil (groups A and C). Control rats received only an equivalent amount of sesame oil (groups B and D).Histopathogenesis Study. Eight to 15 carcinogen-treated rats (group A) were killed 15, 30, 45, 60, 75, 90, 120, 150, 200, or 365 days after DMBA treatment. Eight to 10 control rats (group B) were killed 30, 60, 90, 150, 200, or 365 days after oil treatment. The thoracic, abdominal, and inguinal pairs of mammary glands were processed for whole mount examination according to the method of Beuving et al. (13). The occurrence and characteristics of mammary gland dysplasias and tumors were determined with the aid of a dissecting microscope. Tissues selected for histological examination were processed routinely (13).Tumor Characterization. Parallel groups of rats, DMBAtreatedand control (groups C and D),were palpated weekly for 12 months. Palpable tumors were recorded and classified as follows. Progressively growing tumors (PGTs) were...

show abstract

Section: Methodsmentioning

confidence: 95%

“…It is known that in 30-40% of individuals mammary cancer is hormone responsive, whereas in the remainder it is not (7)(8)(9). At present it is not known if the histopathogenesis of these two forms of mammary cancer differ.…”

mentioning

confidence: 99%

Histopathogenesis of 7,12-diemthylbenz(a)anthracene-induced rat mammary tumors.

Haslam

Bern

1977

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Serum PRL levels in rats with DMBAinduced mammary tumors were greatly suppressed by treatment with bromocriptine 1977; Leung and Sasaki, 1975;Manni et al, 1977;McGuire et al, 1974;Meites, 1972). It has been reported that PRL is the dominant hormone involved in the growth of DMBA-induced mammary tumors since estrogens are ineffective in stimulating tumor growth in rats after hypophysectomy (Sterental et al, 1963) and after the administration of lergotrile which inhibits the secretion of PRL (Manni et al, 1977 In the present experiment, we found that serum PRL levels were suppressed by tamoxifen treatment in these tumor bearing animals.…”

Section: Analysis Of Datamentioning

confidence: 99%

“…It is well known that growth of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA) is dependent mostly on the action of estrogens and prolactin (PRL) (Asselin et al, 1977;Heuson et al, 1971/72;Leung and Sasaki, 1975;Manni et al, 1977;McGuire et al, 1974;Meites, 1972;Sterental et al, 1963). The response of a hormone-dependent tumor is likely to depend not only on the circulating hormone levels but also on hormone receptor levels.…”

mentioning

confidence: 99%

Effects of bromocriptine and tamoxifen on growth and hormone receptor levels of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats.

et al. 1983

View full text Add to dashboard Cite

The role of prolactin (PRL) and estrogen in the growth of 7,12-dimethylbenz(a)-anthracene (DMBA)-induced rat mammary tumors was investigated.Tumor growth was suppressed by both bromocriptine and tamoxifen.Combined administration of ovine PRL and tamoxifen attenuated the inhibitory action of tamoxifen on tumor growth. Serum PRL levels were decreased by both bromocriptine and tamoxifen administration.Estrogen receptors (ER) in tumor tissues were decreased in number by tamoxifen, but not by bromocriptine.Progesterone receptors (PgR) in DMBAinduced mammary tumors were abolished by tamoxifen and significantly reduced by bromocriptine.Combined administration of ovine PRL with tamoxifen attenuated the inhibition of PgR induced by tamoxifen alone, while ER remained undetectable. Specific PRL binding to the liver was significantly reduced by treatment with bromocriptine, tamoxifen and tamoxifen plus ovine PRL, whereas PRL receptors in mammary tumor were not influenced by these drugs.These results suggest that PRL may stimulate DMBA-induced tumor growth independently of ER and that a part of the inhibiting effect of tamoxifen on tumor growth may be explained by the decreased PRL secretion.

show abstract

“…Thus, breast cancer re mission has been demonstrated following abla tive endocrine therapy (1,2). Antiestrogen drugs such as tamoxifen (TAM) are now wide ly used for endocrine treatment of breast can cers, and they provide successful management of hormone-dependent breast cancers (3)(4)(5).…”

mentioning

confidence: 99%

Antitumor Effects of Droloxifene, a New Antiestrogen Drug, against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats

Kawamura

Mizota²,

Kondo³

et al. 1991

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-The antitumor effects of droloxifene (DROL, (E)-a-[p-[2-(dimethyl amino)ethoxy]-phenyl]-a-ethyl-3-stilbenol), a new antiestrogen drug, on 7,12-dimethyl benz(a)anthracene (DMBA)-induced estrogen-dependent mammary tumors in rats were studied and compared with those of tamoxifen (TAM). Mammary tumors appeared from about 2 months after p.o. administration of DMBA to female rats, and all of them were estrogen receptor (ER) and progesterone receptor positive. DROL and TAM (p.o.) inhibited the growth of the tumors. Both drugs inhibited the binding of 125I-estradiol-17,9 to ER in the cytosol of the tumor in vitro, and the effect of DROL was much stronger than that of TAM. When 3H-estradiol-17(3 (3H-E2) was given s.c. to rats with the mammary tumors, 3H-E2 accumulated in the tumors, uteri and vaginae in which the ER levels are known to be high, but was low in the heart, in which the ER levels are normally low. DROL and TAM decreased the levels of 3H E2 in the tumors, uteri and vaginae, but had no effect in the hearts. When DROL or TAM was given p.o. to rats daily for 7 consecutive days after administration of DMBA, they inhibited the induction of mammary tumors by DMBA. From these re sults, DROL inhibits the growth and the initiation of DMBA-induced mammary tumors by inhibiting the binding of estrogen to its receptor.

show abstract

Hormone dependence in breast cancer

Cited by 78 publications

References 94 publications

Histopathogenesis of 7,12-diemthylbenz(a)anthracene-induced rat mammary tumors.

Histopathogenesis of 7,12-diemthylbenz(a)anthracene-induced rat mammary tumors.

Effects of bromocriptine and tamoxifen on growth and hormone receptor levels of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats.

Antitumor Effects of Droloxifene, a New Antiestrogen Drug, against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats

Contact Info

Product

Resources

About