Aromatase inhibitors of the third generation in endocrine therapy of breast cancer and endometrial cancer: the successes and failures of the combination therapy

2016 ◽  
Vol 14 (2) ◽  
pp. 47-57
Author(s):  
Ekaterina P Fadeeva ◽  
Alla S Lisyanskaya ◽  
Georgiy M Manikhas ◽  
Ruslan I Glushakov ◽  
Natalia I Tapilskaya
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Endometrial Cancer ◽  
Combination Therapy ◽  
Endocrine Therapy ◽  
Endometrial Stromal Sarcoma ◽  
Current Evidence ◽  
Third Generation ◽  
The Third ◽  
Stromal Sarcoma

This review provides the current evidence of clinical studies on the effectiveness of endocrine therapy for breast cancer and endometrial cancer, including endometrial stromal sarcoma, by aromatase inhibitor (AI) III generation. The review presents dates from clinical trials comparing the effectiveness of AI and tamoxifen, as well as dates on combination therapy AI with inhibitors of mTOR pathway (BOLERO-2 trial), an antiestrogen (SWOG S0226, FACT, FIRST trials), an inhibitor of CDK4 / 6 (PALOMA -1 trial) and other drugs.

Primary Extra-Uterine Endometrial Stromal Sarcoma and Synchronous Breast Cancer: A Double Whammy: A Case report

2021 ◽  
Author(s):  
Pavneet Kohli ◽  
Prasanth Penumadu ◽  
Neelesh Srivastava ◽  
Bheemanathi Hanuman Srinivas ◽  
Vidyalakshmi Rangarajan
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Endometrial Stromal Sarcoma ◽  
Stromal Sarcoma ◽  
Synchronous Breast Cancer

Low-grade endometrial stromal sarcoma developing in a postmenopausal woman under toremifene treatment for breast cancer

2012 ◽  
Vol 39 (1) ◽  
pp. 424-429 ◽  
Author(s):  
Tomoko Kashiyama ◽  
Katsutoshi Oda ◽  
Kei Kawana ◽  
Takahide Arimoto ◽  
Yukiko Kanetaka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Woman ◽  
Endometrial Stromal Sarcoma ◽  
Low Grade ◽  
Stromal Sarcoma

scholarly journals Dutch Breast Cancer Trialists' Group (BOOG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 61-79
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Phase Iii ◽  
List Type ◽  
First Line ◽  
Open Label ◽  
Phase Iii Study

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Dutch breast cancer trialists' group (BOOG). Clinical trials include:An open label randomized (inter)national multicenter comparative trial of 5 years adjuvant endocrine therapy with an LHRH agonist plus an aromatase inhibitor (goserelin + anastrozole) versus five courses FE90C chemotherapy followed by the same endocrine therapy in pre- or perimenopausal patients with hormone receptor-positive primary breast cancer (PRemenopausal Optimal Management IS Endocrine therapy). BOOG 2002-01/PROMISE. ISRCTN23561723Open label, comparative, randomized, multicenter, study of trastuzumab (Herceptin) given with docetaxel (Taxotere) versus sequential single agent therapy with trastuzumab followed by docetaxel as first-line treatment for metastatic breast cancer (MBC) patients with HER2neu overexpression. BOOG 2002-02/HERTAX ISRCTN13770586Micro-metastases and Isolated tumour cells: Robust and Relevant Or Rubbish? The MIRROR study in BREAST CANCER. BOOG 2003-03/ZonMW 3214Radiation dose intensity study in breast cancer in young women: a randomized phase III trial of additional dose to the tumor bed. BOOG 2004-01/Young Boost SRCTN45066831Microarray analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens, a randomized phase III study. MATADOR, BOOG 2005-02, CKTO 2004-04 ISRCTN61893718A prospective randomised, open, multicentre, phase III study to assess different Durations of Anastrozole therapy after 2–3 years Tamoxifen as Adjuvant therapy in postmenopausal women with breast cancer. 2006-01/DATAA randomized, open-label phase III study of first line chemotherapy in elderly metastatic breast cancer patients, comparing intravenous pegylated liposomal doxorubicin with oral capecitabine; and the incorporation of a complete geriatric assessment. 2006-02/OMEGABOOG participation in International studies:. BOOG 2001-01/TEAM trial. BOOG 2001-02/AMAROS (EORTC 10981/22023). BOOG 2002-04/HERA (BIG 1-01/EORTC 10011/BO16348B). BOOG 2003-02 (BIG 1-02/IBCSG 27-02). BOOG 2003-04 (GBG 29). BOOG 2004-02/TBP (GBG 26, BIG 3-05). BOOG 2005-01/CASA (IBCSG 32-05/BIG 1-05). BOOG 2005-03/MINDACT (EORTC 10041, BIG 3-04). BOOG 2006-03/SUPREMO (BIG 2-04). BOOG 2006-04/Adjuvant lapatinib study (BIG 2-06/EGF106708)

Aromatase Inhibitors in the Treatment and Prevention of Breast Cancer

2001 ◽  
Vol 19 (3) ◽  
pp. 881-894 ◽  
Author(s):  
Paul E. Goss ◽  
Kathrin Strasser
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Clinical Status ◽  
Phase Iii ◽  
Type I ◽  
Third Generation ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
The Third

PURPOSE: The purpose of this article is to provide an overview of the current clinical status and possible future applications of aromatase inhibitors in breast cancer. METHODS: A review of the literature on the third-generation aromatase inhibitors was conducted. Some data that have been presented but not published are included. In addition, the designs of ongoing trials with aromatase inhibitors are outlined and the implications of possible results discussed. RESULTS: All of the third-generation oral aromatase inhibitors—letrozole, anastrozole, and vorozole (nonsteroidal, type II) and exemestane (steroidal, type I)—have now been tested in phase III trials as second-line treatment of postmenopausal hormone-dependent breast cancer. They have shown clear superiority compared with the conventional therapies and are therefore considered established second-line hormonal agents. Currently, they are being tested as first-line therapy in the metastatic, adjuvant, and neoadjuvant settings. Preliminary results suggest that the inhibitors might displace tamoxifen as first-line treatment, but further studies are needed to determine this. CONCLUSION: The role of aromatase inhibitors in premenopausal breast cancer and in combination with chemotherapy and other anticancer treatments are areas of future exploration. The ongoing adjuvant trials will provide important data on the long-term safety of aromatase inhibitors, which will help to determine their suitability for use as chemopreventives in healthy women at risk of developing breast cancer.

A Clinical and Pathologic Study of 34 Sarcomas of the Uterus

1981 ◽  
Vol 67 (4) ◽  
pp. 341-348 ◽  
Author(s):  
Rado Kenda ◽  
Giuseppe De Palo ◽  
Salvatore Andreola ◽  
Gaetano Bandieramonte ◽  
Giovanni Lupi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Endometrial Stromal Sarcoma ◽  
Controlled Clinical Trials ◽  
Relapse Free Survival ◽  
Histologic Subtype ◽  
Uterine Sarcomas ◽  
Free Survival ◽  
Stromal Sarcoma ◽  
Pathologic Features ◽  
History Of

The clinical and pathologic features of 34 uterine sarcomas were studied to determine the natural history of the disease. Sixteen patients had leiomyosarcoma, five mixed mesodermal sarcoma, ten endometrial stromal sarcoma, two carcinosarcoma and one endolymphatic stromal myosis. The patients were treated without an unique protocol. At 3 years the actuarial relapse-free survival was 53.6 %: 68.4 % in stage I-II patients and 22.2 % in stage III-IV patients. As regards the histologic subtype mixed mesodermal sarcomas had the best prognosis; endometrial stromal sarcomas the worst. The necessity of a uniform clinical and histologic classification as well as the importance of controlled clinical trials are pointed out.

High-Grade Endometrial Stromal Sarcoma after Tamoxifen Therapy for Breast Cancer

2005 ◽  
Vol 60 (2) ◽  
pp. 117-120 ◽  
Author(s):  
Francesco Sesti ◽  
Lodovico Patrizi ◽  
Beatrice Ermini ◽  
Giampiero Palmieri ◽  
Augusto Orlandi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Stromal Sarcoma ◽  
Tamoxifen Therapy ◽  
High Grade ◽  
Stromal Sarcoma

scholarly journals Neoadjuvant endocrine treatment of women with breast cancer

2011 ◽  
Vol 5 (3) ◽  
pp. 157
Author(s):  
Julian Iturbe ◽  
Ariel Zwenger ◽  
Carlos Vallejo ◽  
Bernardo Leone ◽  
Pablo Leone
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Tumor Volume ◽  
Neoadjuvant Treatment ◽  
Current Evidence ◽  
Endocrine Treatment ◽  
Duration Of Treatment ◽  
Length Of Treatment ◽  
Primary Endocrine Therapy

Neoadjuvant therapy has four goals in breast cancer: decrease tumor volume to operate tumors that initially were inoperable, increase the number of conservative surgeries, evaluate the chemosensitivity in vivo and analyze the management of micrometastases. Neoadjuvant treatment provides a unique setting in which we can monitor clinical, pathological, proliferative and molecular responses. Combining different strategies such us surgery, radiation therapy, chemotherapy, and endocrine therapy has contributed substantially to the survival improvement in breast cancer. Thirdgeneration aromatase inhibitors have proven to be superior to tamoxifen in the adjuvant and, more recently, the neoadjuvant treatment of postmenopausal patients. The need to define how to select the patients that will benefit the most from these therapies, the optimal duration of treatment, the bestmethod to evaluate the treatment response, the identification of predictive factors for response, and the superiority of certain endocrine agents over others have been reviewed. We have carried out a critical analysis of the current literature on the utilization of endocrine therapy in the neoadjuvant setting for breast cancer. This review discusses the current evidence regarding primary endocrine therapy and the current opinions on length of treatment and measurement of response prior to surgery.

High-grade endometrial stromal sarcoma after treatment with tamoxifen in a patient treated for breast cancer

2003 ◽  
Vol 13 (5) ◽  
pp. 690-692 ◽  
Author(s):  
Y. Saga ◽  
M. Ohwada ◽  
T. Kohno ◽  
N. Takayashiki ◽  
M. Suzuki
Keyword(s):  
Breast Cancer ◽  
Endometrial Stromal Sarcoma ◽  
Tamoxifen Therapy ◽  
Low Grade ◽  
High Grade ◽  
Stromal Sarcoma ◽  
Endometrial Epithelium ◽  
Sarcoma Cells ◽  
Disease Free

Tamoxifen has been widely used in breast cancer treatment. In recent years, the occurrence of uterine malignancies in patients receiving long-term tamoxifen therapy has attracted attention. Most of these malignancies are endometrial adenocarcinomas, but low-grade endometrial stromal sarcomas have occasionally been reported. Here we report a woman who developed a high-grade endometrial stromal sarcoma after receiving postmastectomy tamoxifen therapy. The patient underwent a left mastectomy at age 45 and subsequently received oral tamoxifen for 3 years. At age 51, she was diagnosed with endometrial stromal sarcoma, for which a radical hysterectomy was performed. High-grade endometrial stromal sarcoma was diagnosed by postoperative histologic examination. Immunostaining for the estrogen receptor was negative in sarcoma cells, but positive in the residual endometrial epithelium and the nucleus of adjacent stromal cells within the tumor. The patient has now survived disease-free for 37 months after surgery.

Fulvestrant in advanced breast cancer following following failure of tamoxifen and a third generation aromatase inhibitor

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1073-1073
Author(s):  
J. Wang ◽  
S. Jain ◽  
W. Heller ◽  
D. Mackie ◽  
V. Watson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Aromatase Inhibitor ◽  
Endocrine Therapy ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Third Generation

1073 Background: Endocrine therapy is a key modality in the management of estrogen receptor positive metastatic breast cancer. Fulvestrant (ICI 182,780) is an estrogen receptor downregulator. It has previously been shown to be as effective as anastrozole in patients who had previously progressed on tamoxifen. Methods: A retrospective study was carried out of metastatic breast cancer patients treated at Charing Cross Hospital between 2002–2005 who had received fulvestrant following treatment failure with tamoxifen and a third generation aromatase inhibitor. All patients were postmenopausal and received fulvestrant 250mg IM every 28 days. Measurable disease was assessed by response evaluation criteria in solid tumors (RECIST). Results: A total of 45 patients were identified with a median age of 60 (range 36 to 90). The ER status was known in 95% (n=43) of patients and was positive in all cases, it was unknown in 2% (n=2). At the time of commencing fulvestrant, 96% (n=43) had metastatic disease and 4% (n=2) locally advanced disease. All patients had received at least 2 lines of prior endocrine therapy (including adjuvant therapy), at time of starting fulvestrant the median number of prior regimens was 3 (range 3–5). Fulvestrant was administered for a median of 4 months (range 1 to 20 months), with 4 patients currently still receiving therapy as of 1 November 2006. Of the 45 patients, 2.2% (n=1) achieved a partial response, while 31% (n=14) achieved stable disease for at least 6 months. Thus, 33.3% (n=15) obtained clinical benefit (defined as PR or SD for at least 6 months). The response rates based on line of therapy will be presented. Of the 45 patients, 41 were evaluable for survival data. The median survival of the remaining patients from the start of fulvestrant therapy was 9 months (range 1 to 48 months). Of the 44 patients, 14% (n=6) remain alive. The treatment was well tolerated and toxicity data will be presented. Conclusions: Fulvestrant is well tolerated and is efficacious as treatment for advanced breast cancer that has failed tamoxifen and a third generation aromatase inhibitors. No significant financial relationships to disclose.

Expression of type I insulin-like growth factor receptor (IGF1R) in tamoxifen-resistant cells: Implications for cotargeting of IGF1R and estrogen receptor (ER) in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13590-e13590
Author(s):  
Dedra H. Fagan ◽  
Ryan R. Uselman ◽  
Deepali Sachdev ◽  
Douglas Yee
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Endocrine Therapy ◽  
Insulin Like Growth Factor ◽  
Anchorage Independent Growth ◽  
Akt Phosphorylation ◽  
Igf I ◽  
Tamoxifen Resistant

e13590 Background: Crosstalk between the insulin-like growth factor (IGF) and estrogen receptor (ER) systems has been well defined in breast cancer. The majority of anti-IGF1R clinical trials are in estrogen receptor-positive patients who have progressed on prior endocrine therapy; early reports show no benefit for addition of IGF1R inhibitors to endocrine therapy in this setting. Methods: To examine the effectiveness of IGF1R inhibitors, tamoxifen-resistant (TamR) cells were generated in MCF-7L and T47D cells. IGF1R was inhibited by monoclonal antibody (dalotuzumab) or IGF1R/insulin receptor (IR) tyrosine kinase inhibitor (AEW541). Results: TamR cells had diminished levels of IGF1R with unchanged levels of IR. Further, TamR cells failed to respond to IGF-I-induced Akt activation, proliferation, and anchorage-independent growth while retaining responsiveness to both insulin and IGF-II. Dalotuzumab inhibited IGF-I-mediated Akt phosphorylation, proliferation, and anchorage-independent growth in parental cells, but had no effect on TamR cells. AEW541 with equal potency for the IGF1R and IR, inhibited IGF-I-, IGF-II-, and insulin-stimulated Akt phosphorylation, proliferation, and anchorage-independent growth in parental cells. Interestingly, AEW541 also inhibited insulin- and IGF-II-stimulated effects in TamR cells. MCF-7L xenografts from estrogen replete mice were inhibited by dalotuzumab. However, dalotuzumab add no additional benefit to tamoxifen in estrogen depleted mice. Xenograft tumors from tamoxifen treated mice had reduced levels of IGF1R mRNA. Conclusions: Because ER regulates IGF1R mRNA expression, inhibition of IGF1R does not add to tamoxifen growth inhibition of breast cancer cells. Furthermore, inhibition of IR may be necessary to manage tamoxifen resistant breast cancer. The failure of clinical trials of IGF1R inhibitors in endocrine resistant breast cancer could be explained by this crosstalk between the two growth regulatory receptors.

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