• Anti-tumor effects of Letrozole (Femara)

    From PubMed

    The use of drugs, which inhibit estrogen biosynthesis, is an attractive treatment for postmenopausal women with hormone-dependent breast cancer. Estrogen deprivation is most specifically achieved using inhibitors which block the last stage in the biosynthetic sequence, i.e., the conversion of androgens to estrogens by the aromatase enzyme.

    Recently, a new generation of aromatase inhibitors has been developed. Among these, letrozole (Femara) appears to be the most potent. When given orally in milligram amounts per day to postmenopausal women, the drug almost totally inhibits peripheral aromatase and causes a marked reduction in circulating estrogens to levels that are often undetectable in conventional assays. Similarly, neoadjuvant studies demonstrate that letrozole substantially inhibits aromatase activity in both malignant and nonmalignant breast tissues, and markedly suppresses endogenous estrogens within the breast cancers. These studies also illustrate anti-estrogenic and anti-proliferative effects of letrozole in estrogen receptor (ER)-rich tumors. Thus, tumor expression of progesterone receptors and the cell-cycle marker Ki67 is significantly and consistently reduced with treatment.

  • Anti-tumor effects of Letrozole (Femara)

    From PubMed

    The use of drugs, which inhibit estrogen biosynthesis, is an attractive treatment for postmenopausal women with hormone-dependent breast cancer. Estrogen deprivation is most specifically achieved using inhibitors which block the last stage in the biosynthetic sequence, i.e., the conversion of androgens to estrogens by the aromatase enzyme.

    Recently, a new generation of aromatase inhibitors has been developed. Among these, letrozole (Femara) appears to be the most potent. When given orally in milligram amounts per day to postmenopausal women, the drug almost totally inhibits peripheral aromatase and causes a marked reduction in circulating estrogens to levels that are often undetectable in conventional assays. Similarly, neoadjuvant studies demonstrate that letrozole substantially inhibits aromatase activity in both malignant and nonmalignant breast tissues, and markedly suppresses endogenous estrogens within the breast cancers. These studies also illustrate anti-estrogenic and anti-proliferative effects of letrozole in estrogen receptor (ER)-rich tumors. Thus, tumor expression of progesterone receptors and the cell-cycle marker Ki67 is significantly and consistently reduced with treatment.

  • Aromatase Inhibitors in Gynecologic Cancers

    Abstract from PubMed

    The female genital tract is hormonally responsive, and consequently some tumors, which arise within in it, may be treated at least in part, with hormonal manipulation. The range of responses in clinical trials and case reports will be reviewed. Many of these diseases are too rare for clinical trial testing, and in some cases evidence is anecdotal at best. Recurrences of ovarian cancer have been treated with tamoxifen and megesterol acetate with variable response rates from 0 to 56%.

    The favorable toxicity profile of aromatase inhibitors led to trials of these agents for the treatment of relapsed epithelial ovarian cancer. These agents have proved tolerable with minor response rates but a significant disease stabilization rate, which may be prolonged in a minority of cases. It is unclear if these responses may be predicted by estrogen receptor expression or aromatase expression. Anastrazole has also been tried in combination with an EGFR receptor-inhibitor, again showing minor responses but possibly an increase in TTT in some patients. Granulosa cell tumors of the ovary are rare, hormonally sensitive tumors, with reported responses to a variety of hormonal manipulations, including aromatase inhibition. In addition, combined endocrine blockade, including aromatase inhibition, has been tried with reports of success. Endometrial cancers, particularly type I lesions, are often treated with hormonal manipulation, most commonly with progestins, but also with antiestrogens such as tamoxifen. A trial of aromatase inhibition in the treatment of recurrent endometrial cancer showed minimal responses. Endometrial stromal sarcoma, an uncommon uterine malignancy, has shown response to hormonal treatments, with multiple case reports of efficacy of aromatase inhibition. Despite the rarity of some of these tumor types, rare tumor study groups, such as within the Gynecologic Oncology Group, should make an effort to prospectively define the utility of these treatments.

    Click here to go to PubMed

  • ESS: Objective response to Letrozole (Femara)

    Source: Gynecologic Oncology, Volume 82, Issue 2, August 2001, pp. 384-388

    Abstract:
    Background. Low-grade endometrial stromal sarcoma is generally an indolent tumor rich in estrogen and progesterone receptors. Objective responses to hormonal therapy, most commonly with megestrol acetate (Megace), have been reported.

    Case. The patient is a 51-year-old woman who presented with low-grade endometrial stromal sarcoma confined to the uterus in 1991 and was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Approximately 5 years later, the patient had recurrent pelvic disease treated with radiation therapy, followed by an attempt at resection. She was treated with megestrol acetate during the period she received radiation therapy with poor tolerance. Tamoxifen was then given with no tumor response. Megestrol acetate was restarted with progression of disease in the pelvis and abdomen. Letrozole was then given at a daily dose of 2.5 mg with partial response for a duration of 9 months.

    Conclusion. Letrozole at a daily dose of 2.5 mg may be effective in low-grade endometrial stromal sarcoma with positive estrogen receptors.

    Link to article

  • Hormonal therapy of endometrial stromal sarcoma

    Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria.

    PURPOSE OF REVIEW: Low-grade endometrial stromal sarcomas are steroid receptor positive tumors with slow tumor progression and high recurrence rates, which lack established treatment protocols. We present an update on hormonal therapy options. RECENT FINDINGS: In the past, hormonal therapy consisted of progestins for advanced/recurrent/metastatic low-grade endometrial stromal sarcomas. Aromatase inhibitors and gonadotropin-releasing hormone analogues have become new effective alternatives for first and second line treatment. The high recurrence rates after short disease free intervals in low-grade endometrial stromal sarcoma patients were partly due to inadvertent growth stimulation during estrogen-containing hormone replacement therapy and tamoxifen treatment, which - according to current knowledge - are contraindicated. Recently, hormonal therapy has been introduced for the prevention of recurrences. Aromatase inhibitors are becoming the treatment of choice, since progestins are poorly tolerated due to side effects. The effective duration of preventive hormonal therapy is still undetermined. SUMMARY: Hormonal therapy with progestins, aromatase inhibitors and gonadotropin-releasing hormone analogues has become an effective treatment alternative to radiation and chemotherapy for low-grade endometrial stromal sarcoma patients. Preventive hormonal therapy is of particular interest in the setting of concomitant endometriosis.

    View abstract on PubMed

  • Hormonal treatment of metastatic endometrial stromal sarcoma

    From the 2009 ASCO Annual Meeting

    Abstract:

     

    Background:Endometrial stromal sarcomas (ESS) traditionally have been classified as low grade or high grade based on mitotic activity and histologic appearance. High-grade tumors are currently referred to as undifferentiated uterine sarcomas and are not included in this series. ESS are known to have high expression of estrogen and progesterone receptors. This is a retrospective study of patients with metastatic ESS treated with hormonal therapy. Methods: Following approval by the institutional review board all patients diagnosed with ESS from 1987-2007 were identified. Clinical and demographic information were abstracted from the charts and all histologic materials were re-reviewed. Estrogen and progesterone receptor testing was performed utilizing mouse monoclonal antibodies and the Cell Analysis Systems 200 Image analyzer. Survival was calculated using the Kaplan-Meier method and comparisons utilized the log rank test. Results: Thirteen patients with ESS were identified during this period. Seven had disease confined to the uterus. Six had extrauterine disease; 5 patients presented with metastases and 1 patient presented with a pelvic recurrence 20 years following a hysterectomy. All underwent surgical resection except for 1 patient that declined surgery. All 6 patients with metastases had tumors that tested positive for estrogen and progesterone receptors; all were treated with megestrol acetate initially for a period of 1-4 years. Two patients were then changed to maintenance with medroxyprogesterone acetate. Three patients with persistent disease were changed to aromatase inhibitors; 1 to letrozole and 2 to anastrazole. One of these patients has had a complete response and 2 have had stable disease. One patient has been lost to follow-up. Follow-up for the 6 patients was 2-22 years; no known patients died of their disease. Actuarial 2- and 5-year survivals were 80% and 65%, respectively. There was no significant difference in survival between patients with metastases and without metastases. Conclusions: ESS tumors are relatively uncommon and there is an absence of studies to guide treatment of patients with metastases. This experience indicates that these tumors respond well to hormonal manipulation. Treatment with progestins or aromatase inhibitors may result in remission or stable disease.

    Link: http://www.abstract.asco.org/AbstView_65_30210.html

  • Immunological Therapies Can Relieve Aromatase Inhibitor-Related Joint Symptoms in Breast Cancer Survivors

    Reprinted from American Journal of Clinical Oncology, December 2010 - Volume 33 - Issue 6 - pp 557-560, doi: 10.1097/COC.0b013e3181cae782

    Objectives: Aromatase inhibitors can cause joint symptoms. The purpose of this pilot study was to evaluate the feasibility of immunologic therapies for this kind of joint symptoms.

    Methods: A total of 16 postmenopausal women with stage I–III breast cancer with joint symptoms related to Aromatase inhibitors were enrolled. They received immunologic therapies of thymosin α1 1.6 mg, twice a week for 4 weeks. Outcome measures included the Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis index, and the Functional Assessment of Cancer Therapy-General quality of life measure. Interferon-gamma and interleukin-4 were determined to evaluate immunomodulatory activity. Paired Samples Test and linear regression analysis were used to statistics the outcome measures.

  • Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma

    Department of Oncology, Avicenne Hospital, Bobigny, France.

    Endometrial stromal sarcoma (ESS) is a rare neoplasm, mainly observed in premenopausal women. We describe two women 44 and 34 years old at the time ESS diagnosis, who developed lung metastases 3 and 6 years, respectively, after initial treatment: hysterectomy without (case 1) or with oophorectomy (case 2), followed by hormone replacement therapy (HRT) for the latter. Their estrogen (ER) and progesterone receptors (PR) were analyzed biochemically in metastatic lung tissue, yielding respective concentrations of ER 242 and 184, and PR 910 and 100 fmol/mg of cytosol protein. Both patients started treatment with the aromatase inhibitor aminoglutethimide (500 mg qid) after surgery for the first patient and after stopping HRT for the second. Under aromatase-inhibitor therapy, both patients achieved a complete response, patient 1 remains disease- free with 14+ years of follow-up, and patient 2 with 7+ years. Our data suggest that an aromatase inhibitor may be an effective treatment for ESS. Furthermore, routine ER and PR analyses could be useful to predict the response to hormonal therapy in ESS.

    View abstract on PubMed

  • Management of late recurrence of a low-grade ESS: Treatment with Letrozole

    From PubMed, Anticancer Res. 2007 Sep-Oct;27(5B):3477-80.

    Low grade endometrial stromal sarcoma (LGESS) is a rare disease. LGESS usually expresses steroidal receptors and is regarded to be hormone-sensitive. Due to the rarity of the tumor, only few case series have been published so far. Here, we report the case of a 36-year-old woman who underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant radiotherapy for a G1 LGESS in 1991. Twelve years later she presented to us with pelvic and peritoneal masses. The patient was treated with letrozole (Femara) achieving a partial response which is lasting 39 months. Treatment is ongoing. Aromatase inhibitors represent an interesting treatment option for LGESS.

    Link to abstract

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