Tamoxifen and endometrial carcinoma: Alterations in estrogen and progesterone receptors in untreated patients and combination hormonal therapy in advanced neoplasia

Carlson, John A.; Allegra, Joseph C.; Wittliff, James L.

doi:10.1016/0002-9378(84)90187-x

Cited by 65 publications

(10 citation statements)

References 9 publications

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“…However, several good quality studies reported an average response rate of 25% to progestin in an unselected population, which is similar to the responses to tamoxifen and progestin/tamoxifen found in this review (65, 66). The rationale for adding tamoxifen to progestin is to counteract the down regulation of the progesterone receptor that is induced by progestin treatment in order to prolong the duration of response (67, 68). Different combinations of progestin and tamoxifen have been explored.…”

Section: Discussionmentioning

confidence: 99%

Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review

Weelden¹,

Massuger²,

Enitec

et al. 2019

Front. Oncol.

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Introduction: Hormonal therapy in endometrial cancer (EC) is used for patients who wish to preserve fertility and for patients with advanced or recurrent disease in a palliative setting. First line hormonal therapy consists of treatment with progestins, which has a response rate of 25% in an unselected population. Treatment with anti-estrogens is an alternative hormonal therapy option, but there is limited data on the effect and side-effects of anti-estrogens in EC. Therefore, we performed a systematic review to investigate the response rate and toxicity of anti-estrogenic therapy in patients with endometrial cancer. Methods: A systematic search in electronic databases was performed to identify studies on selective estrogen receptor modulators (SERM) and down-regulators (SERD) and aromatase inhibitors that reported on response rates (RR) among EC patients. Outcome in estrogen receptor (ER) positive and negative disease was assessed independently. Results: Sixteen studies on advanced stage and recurrent EC were included. Ten studies investigated anti-estrogen monotherapy and seven investigated a combination of anti-estrogenic drugs with either progestin or targeted treatment. Due to heterogeneity in patient population, no meta-analysis was performed. The median age of the patients in the included studies ranged from 61 to 71 years and the proportion of low grade tumors ranged from 38 to 80%. The RR for tamoxifen ranged from 10 to 53%, for other SERMs and SERDs 9–31%, for aromatase inhibitors from 8 to 9%, for combined tamoxifen/progestin treatment 19–58%, for combined chemo- and hormonal therapy 43% and for combination of anti-estrogenic treatment with mammalian target of rapamycin (mTOR) inhibitors 14–31%. Toxicity consisted mainly of nausea and thrombotic events and was higher in combination therapy of chemotherapy and hormonal therapy and hormonal therapy and mTOR inhibitors compared to other therapies. Conclusion: Tamoxifen or a combination of tamoxifen and progestin should be the preferred choice when selecting second line hormonal treatment because the RRs are similar to first line progestin treatment and the toxicity is low. The response can be optimized by selecting patients with endometrioid tumors and positive estrogen receptor status, which should be based on a pretreatment biopsy.

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Section: Discussionmentioning

confidence: 99%

Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review

Weelden¹,

Massuger²,

Enitec

et al. 2019

Front. Oncol.

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“…Tamoxifen alone, or in combination with progestagens, has well established inhibitory activity for advanced and recurrent endometrial carcinoma (Rendina et al 1984; Quinn & Campbell 1989). In view of the possible down‐regulation of progesterone receptors by continuous administration of progesterone alone (Zaino et al 1985) and the demonstration of an increase of progesterone receptors in response to tamoxifen (Carlson et al 1984), we decided to use combination therapy. This case is the first recorded cure and successful pregnancy with combined anti‐oestrogen and progesterone, although we realise that our patient may have done as well with megestrol acetate alone.…”

Section: Discussionmentioning

confidence: 99%

Successful pregnancy after tamoxifen and megestrol acetate therapy for endometrial carcinoma

Lai

Hsueh

Chad

et al. 1994

BJOG

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Case reportA 31 year old woman presented in August 1991, and her main complaint was of primary infertility and menorrhagia which she had had for two years. Her basal body temperature record showed an anovulatory pattern. She was of average stature and did not appear malnourished.No hirsutism was noted. Hormone profiles including plasma oestradiol, testosterone, prolactin, follicle stimulating hormone, luteinising hormone, diurnal cortisol and thyroid function tests were normal. Hysterosalpingography showed filling defects in the endometrial cavity and confirmed bilateral tuba1 patency. A hysteroscopic examination was performed, anticipating demonstration of a submucosal leiomyoma or endometrial polyp. Multiple endometrial polypoid masses were biopsied via the hysteroscope, followed by endometrial curettage. The histology report identified a welldifferentiated adenocarcinoma of the endometrium (Fig. 1). Fig. 1. A well differentiated adenocarcinoma. Stromal invasion is evident with the presence of confluent, cribriform glands with little or no intervening stroma. Other areas (not illustrated) showed squamous metaplasia and stromal fibrosis. (H 8c E, x 120).A fractional dilatation and curettage and cervical biopsy were carried out to collect specimens for progesterone and oestrogen receptor assay and also to confirm that there was no extension of tumour to the cervix. Both the receptor assays were positive (oestrogen receptor = 68.3 fmol/mg protein ; progesterone receptor = 99.8 fmol/mg protein). Flow cytometric DNA analysis of the tumour also was performed and revealed diploidy with low proliferative activity (%S = 3.1, %G2M = 5.9). Subsequent investigations, including a chest X-ray, complete blood count and biochemistry, blood sugar, and tumour marker (CA-125, CEA, P-hCG, and AFP) levels were normal. Duplex vaginal sonography showed normal adnexa and a residual endometrial lesion without myometrial invasion with absence of Doppler flow signal and high resistance indices of the uterine arteries. Pelvic and abdominal computerised tomography (CT) scan showed nonenlarged lymph nodes and normal intra-abdominal and pelvic organs, except for an enlarged uterus with an intrauterine lesion.The risks and potential benefits of primary hormone therapy, instead of a standard extirpative surgical approach, were discussed with the patient and she chose hormone therapy. Treatment with tamoxifen (30 mg) and megestrol acetate (160 mg) daily was given.Magnetic resonance imaging (MRI) was not available in our hospital when the treatment began, but when it became available two months later the woman had a negative MRI examination with a thin regular endometrium and intact junctional zone. At two months after hormone therapy began she had a fractional dilatation and curettage which did not identify any residual malignancy (Fig. 2).She continued on hormone therapy and had serial monitoring studies, including sonography, CT or MRI scans, and tumour markers. Four months after treatment began, repeat hysteroscopy and endometrial curettage ...

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“…In contrast, in both clinical [l&20] and nude mouse [20,37] studies TAM has been shown to increase the PgR content of endometrial carcinoma tissue. However, in clinical trials sequential or simultaneous administration of MPA and TAM has not been superior to that of MPA alone [ 15,19,22].…”

Section: Discussionmentioning

confidence: 99%

“…Zaino et al [21] have shown greater regression of nude mouse tumors with sequential use of TAM and MPA than could be obtained with MPA alone. However, in the few clinical trials performed, simultaneous and sequential use of these agents has not been shown to increase the response rate over that achieved with MPA alone [15,19,22].…”

Section: Introductionmentioning

confidence: 99%

In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate

Grénman

Roberts

England

et al. 1988

Gynecologic Oncology

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The growth inhibitory effects of medroxyprogesterone acetate (MPA) and tamoxifen (TAM) were tested on three long-established endometrial carcinoma cell lines (HEC-1, KLE, and RL95-2) and on UM-EC-1, a new endometrial carcinoma cell line established in our laboratory. MPA and TAM were used in growth experiments either alone, simultaneously, or sequentially. The MCF-7 breast cancer cell line was used as a control. None of the endometrial carcinoma cell lines showed significant sensitivity to 0.1-10 microM MPA. In contrast, 10 days exposure to 5 microM TAM induced 83 and 70% growth inhibition in HEC-1 and KLE cultures, whereas the growth of UM-EC-1 was inhibited by 99.7% and RL95-2 cultures by 100%. TAM-induced growth inhibition was reversible since all cell lines resumed logarithmic growth when TAM was removed from the culture medium. Addition of 17 beta-estradiol (E2) to the culture medium did not accelerate recovery, and reversal of TAM-induced growth inhibition was not seen when TAM and E2 were added simultaneously. This is consistent with our finding that, except for MCF-7, these cell lines did not show detectable estrogen receptor (ER) activity in assays performed at the time of these experiments. When treated sequentially with TAM and MPA, all cell lines resumed logarithmic growth when medium containing TAM was replaced with medium containing MPA. Simultaneous exposure to 5 microM MPA and 5 microM TAM resulted in a slight additive growth inhibitory effects only in KLE cultures. Our results show that MPA does not have growth inhibitory effects in these endometrial carcinoma cell cultures, whereas TAM exerts a potent inhibitory effect that is not reversed by estrogen and may thus be mediated through a mechanism different from blockade of ER. In vitro results with the UM-EC-1 cell line correlated with the clinical response of the cell line donor. Her disease progressed during postoperative MPA therapy, but subsequently she responded to TAM therapy.

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Tamoxifen and endometrial carcinoma: Alterations in estrogen and progesterone receptors in untreated patients and combination hormonal therapy in advanced neoplasia

Cited by 65 publications

References 9 publications

Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review

Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review

Successful pregnancy after tamoxifen and megestrol acetate therapy for endometrial carcinoma

In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate

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