Tamoxifen in Platinum-Refractory Ovarian Cancer: A Gynecologic Oncology Group Ancillary Report

Markman, Maurie; Iseminger, Karen; Hatch, Kenneth D.; Creasman, William T.; Barnes, Willard A.; DuBeshter, Brent

doi:10.1006/gyno.1996.0181

Cited by 141 publications

(64 citation statements)

References 4 publications

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“…Although the majority of primary ovarian tumors express ERs (26), the efficacy of endocrine therapies has not been adequately evaluated in ovarian cancer. Clinical studies of tamoxifen in a small number of chemoresistant ovarian cancer patients have demonstrated that a small subset of unselected patients responds to tamoxifen treatment (26)(27)(28). However, a recent study has demonstrated that preselection of ovarian cancer patients according to ER status results in a significantly higher percentage of patients responding to antihormonal therapy (29).…”

Section: Hoxb13 Abrogates the Antagonistic Effect Of Tamoxifenmentioning

confidence: 99%

HOXB13 promotes ovarian cancer progression

Miao

Wang

Provencher

et al. 2007

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

105

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Deregulated expression of HOXB13 in a subset of estrogen receptor-positive breast cancer patients treated with tamoxifen monotherapy is associated with an aggressive clinical course and poor outcome. Because the ovary is another hormone-responsive organ, we investigated whether HOXB13 plays a role in ovarian cancer progression. We show that HOXB13 is expressed in multiple human ovarian cancer cell lines and tumors and that knockdown of endogenous HOXB13 by RNA interference in human ovarian cancer cell lines is associated with reduced cell proliferation. Ectopic expression of HOXB13 is capable of transforming p53 ؊/؊ mouse embryonic fibroblasts and promotes cell proliferation and anchorage-independent growth in mouse ovarian cancer cell lines that contain genetic alterations in p53, myc, and ras. In this genetically defined cell line model of ovarian cancer, we demonstrate that HOXB13 collaborates with activated ras to markedly promote tumor growth in vivo and that HOXB13 confers resistance to tamoxifen-mediated apoptosis. Taken together, our results support a pro-proliferative and pro-survival role for HOXB13 in ovarian cancer.T he HOX family of homeobox genes is an important group of developmental transcriptional regulators that are critical for various aspects of differentiation and morphogenesis (1). Similar to other genes that regulate normal growth and differentiation, HOX genes have been implicated in different aspects of the oncogenic process, because ectopic expression of HOX genes promotes cellular transformation in vitro and tumorigenesis in vivo (2). Of particular interest to human tumorigenesis is the observation that various human tumors including breast, colon, prostate, and lung carcinomas display altered HOX gene expression (3-7). Several HOX family members have been implicated in ovarian cancer differentiation (8, 9), although it is unknown whether HOX genes play a direct role in ovarian cancer progression.We recently demonstrated that dysregulated HOXB13 expression in human breast cancer is directly correlated with poor clinical outcome in estrogen receptor (ER)-positive breast cancer patients treated with tamoxifen monotherapy (10). In preliminary functional studies, we demonstrated that ectopic expression of HOXB13 in a nontransformed human mammary epithelial cell confers increased cell migration and invasion, two characteristics associated with tumor aggressiveness (10). Consistent with a possible role in human tumorigenesis, others have recently shown that HOXB13 is overexpressed in human endometrial, ovarian, and cervical carcinomas and that overexpression of HOXB13 is associated with the invasiveness of ovarian and endometrial cancer cells (11-13). Collectively, these observations suggest that HOXB13 may play an important role in tumors arising from endocrine-responsive organs. Herein, we characterized the expression of HOXB13 in ovarian cancer cell lines and tumors. Furthermore, we investigated the potential growth modulatory role of HOXB13 in vitro and in a genetically defined mouse mod...

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Section: Hoxb13 Abrogates the Antagonistic Effect Of Tamoxifenmentioning

confidence: 99%

HOXB13 promotes ovarian cancer progression

Miao

Wang

Provencher

et al. 2007

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

105

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“…8 out of 9 patients with high estrogen receptor rate, full remission has been obtained (20,21). In another extensive study; chemohormontheraphy was examined in the patients who had not received any treatment with advanced disease, 100 patients have been treated with the combination of cisplatin and doxorubicin, and half of these patients have been concurrently started on tamoxifen.…”

Section: Discussionmentioning

confidence: 99%

Hormonotherapy in the Management of Recurrent Ovarian Cancer

Külhan¹,

Kulhan²,

Naykı³

et al. 2016

IOSR

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“…A standard definition of platinum resistance was used: progression of disease while receiving carboplatin or cisplatin, or recurrence of disease within 6 months of completion of therapy. 4,16 The resistance is considered primary if it occurs during or following the initial treatment. The resistance is said to be secondary if it occurs during or following platinum retreatment of recurrent disease.…”

Section: Methodsmentioning

confidence: 99%

Long term follow-up of patients with recurrent ovarian cancer after Ad p53 gene replacement with SCH 58500

Buller

Shahin

Horowitz³

et al. 2002

Cancer Gene Ther

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Objective: We have previously reported the safety, efficient gene transfer, and favorable CA125 responses of individuals with recurrent ovarian cancer treated by p53 gene replacement with the adenoviral vector SCH 58500. The purpose of the present investigation was to evaluate the long -term follow -up of these heavily pretreated patients subsequent to SCH 58500 dosing. Methods: Patients ( n = 36 ) were treated with either single -dose SCH 58500 in the phase I study or with multiple doses ( MD ) of SCH 58500 over multiple cycles in combination of platinum -based chemotherapy in the phase I / II portion of the study. Five patients were initially treated in the single -dose group and re -enrolled in the MD group. The MD group was evaluated both without the reenrolled patients as MD1 ( n = 19 ), and as MD2 ( n = 24 ), which included them. Patients who were only treated on the single -dose arm were designated as SD ( n = 12 ). Most patients received additional chemotherapy at the discretion of their physicians on completion of the trial. The current analysis is a retrospective sequential cohort survival analysis. Results: The first patient was treated in March 1997 and the last patient completed SCH 58500 in September 1998. There was no difference in age at diagnosis, Karnofsky performance status, interval between diagnosis to SCH 58500, prior cycles or regimen of chemotherapy, platinum -free interval, percent platinum refractory patients, pretreatment CA125, or largest tumor volume between groups. Both MD groups had a slightly longer chemotherapy -free interval before SCH 58500 than the SD group. Median survival of individuals who received MD SCH 58500 with chemotherapy was 12 -13.0 months, compared to only 5 months for those treated with SD SCH 58500. There are 10 long -term survivors more than 20 months after MD treatment for recurrent disease compared to only 2 long -term survivors after SD SCH 58500. Conclusion: The 12 -to 13.0 -month median survival in a heavily pretreated population with recurrent ovarian cancer compares favorably to the 16 -month median survival for individuals treated with paclitaxel at the time of initial recurrence of this disease and is more than double the 5 -month survival seen with palliative radiotherapy or paclitaxel failure. These data suggest that further study of SCH58500 is clearly indicated.

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Tamoxifen in Platinum-Refractory Ovarian Cancer: A Gynecologic Oncology Group Ancillary Report

Cited by 141 publications

References 4 publications

HOXB13 promotes ovarian cancer progression

HOXB13 promotes ovarian cancer progression

Hormonotherapy in the Management of Recurrent Ovarian Cancer

Long term follow-up of patients with recurrent ovarian cancer after Ad p53 gene replacement with SCH 58500

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