Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is only one previous report of an estrogen-secreting adrenal tumor occurring in a woman during reproductive years. Our patient presented with mild hirsutism associated with menstrual bleeding every 3-6 weeks. The occurrence of apparently intermenstrual bleeding prompted an evaluation of estrogen levels. Markedly elevated plasma estrone levels were found (860-2305 pmol/L; normal, 50-340). Lesser relative elevations in 11-deoxycortisol and androstenedione were noted. Computed tomographic scanning of the adrenal glands identified a large tumor, which was subsequently resected. Estrone levels fell to 120 pmol/L, and all other abnormalities were corrected. Eighteen months after adrenalectomy, ovulation occurred regularly, and steroid levels were entirely normal. Steroid production in a cell suspension made from tissue obtained from the 190-g tumor was compared with that occurring in normal human adrenal cells. The production of estrone by the tumor cells was 40-fold greater than that by normal adrenal cells. There was also a mild excess of 11-deoxycortisol produced by tumor cells, but the tumor cells were less than 50% as efficient as normal cells in producing cortisol, dehydroepiandrosterone, androstenedione, testosterone, and dehydroepiandrosterone sulfate. Examination of the steroid profile in plasma occurring in three other patients with adrenal tumors reveals that while elevations in estrone occur frequently, this is usually due to the peripheral conversion of very high levels of androstenedione. Estrone, androstenedione, and 11-deoxycortisol plasma levels were elevated in all four patients; dehydroepiandrosterone sulfate was elevated in only two of four patients. After resection of one of these tumors, all steroid levels remained normal despite the occurrence of extensive metastases. These observations confirm the difficulty of making a diagnosis of estrogen excess in a woman during reproductive years because of the paucity of physical signs. The acquisition of aromatase activity was clearly demonstrated by tumor cells from our patient in vitro. Elevated plasma concentrations of estrone, androstenedione, and 11-deoxycortisol provide useful markers for adrenal tumors, but no one steroid can be relied upon in all tumors, and metastases may lack the steroidogenic capabilities of the primary tumor.
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PMID:Steroidogenesis in an estrogen-producing adrenal tumor in a young woman: comparison with steroid profiles associated with cortisol- and androgen-producing tumors. 229 37

Four cell lines, each derived from a primary tumor from a patient with breast carcinoma, were grown to confluence in alpha-Minimum Essential Medium with 15% fetal calf serum and incubated for 24 h with [3H]androstenedione. The two lines (SA and PP) with the lowest formation of estrone and estradiol (less than 0.1% conversion) were the most active in the formation of the 5 alpha-reduced androgen metabolites androsterone (AND), 5 alpha-androstanedione (5 alpha-A-dione), and dihydrotestosterone (DHT). The two lines with the highest aromatase activity (DM and MD) had the lowest formation of 5 alpha-reduced metabolites. To determine if the 5 alpha-reduced androgen metabolites formed within the breast carcinoma cells could influence aromatase activity, the MD line was further studied. After 24-h preincubation with AND, DHT, or 5 alpha-A-dione at concentrations of 10(-6), 10(-7), and 10(-8) M, [3H]androstenedione was added to the culture medium, and aliquots were removed at 0, 4, 8, and 24 h. An 8-h incubation period was found to be optimum for inhibition studies. In comparison to control levels of estrone (2.5%) and estradiol (0.35%) formation, inhibition of aromatization was evident with all three compounds at 10(-8) M, with 5 alpha-A-dione producing the greatest inhibition (50%). At 10(-7) M, inhibition ranged from 45% (AND) to 70% (5 alpha-A-dione), and at 10(-6) M, inhibition was greater than 90% for each compound. 5 alpha-A-dione produced slightly greater inhibition than AND or DHT at each concentration tested. Since each of these compounds was capable of inhibiting aromatization, the cumulative effect of these 5 alpha-reduced metabolites could be an important factor in the intracellular regulation of aromatase activity.
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PMID:The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture. 669 45

An estrogen (E) independent sub-clone (EIIL) was separated from a human endometrial carcinoma cell line, Ishikawa, by culturing the wild type under an E free condition for 350 days. The cells were then implanted into nude mice subcutaneously and tumors allowed to develop for 35 days. The primary lesions were then excised to stimulate recurrence. One animal developed recurrence with multiple distant metastases. The primary tumor and metastatic tumors from the animal were studied for ErbB-2 expression by immunohystochemical techniques or by a reverse transcription followed by polymerase chain reaction (RT-PCR). Expressions of epidermal growth factor (EGF) receptors, aromatase, nidogen, E receptors, hepatocyte growth factors (HGF) and beta-actin were also examined. The results showed that metastatic lesions expressed high levels of ErbB-2, nidogen and aromatase but unchanged levels of EGF receptors and HGF. The metastatic lesions expressed one third of the E receptors which were detected in the EIIL in vitro. These observations suggest that a decrease in ER along with increased expression of nidogen and aromatase is associated with the process of metastasis and the model appears to be of value in studying the process of the acquisition of a metastatic phenotype.
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PMID:[Establishment of metastatic sub-clone from estrogen independent Ishikawa cells and its characterization in vitro and in vivo]. 769 85

Treatments for men with breast cancer are based largely on accepted regimens for women with the disease. Surgical treatment of the primary tumor should be a mastectomy. Lymph node assessment can be done by conventional axillary node dissection or, similar to selected women with small primary tumors, by sentinel node dissection. Decisions regarding adjuvant systemic treatment should be made on the same basis as for women. Axillary node status, tumor size, hormone receptor status, and the health of the patient are important considerations in determining what adjuvant treatment is offered. The role of radiation after mastectomy in men is not well defined, but radiation should be used in patients at high risk for local recurrence. For patients with metastatic disease, treatment is based on the hormone receptor status of the tumor and is similar to the treatment for women. Because most men with breast cancer have hormone receptor-positive disease, hormonal therapy is a mainstay of treatment and tamoxifen remains the front-line drug of choice, although the latest generation of aromatase inhibitors have supplanted tamoxifen as a first-line therapy for women. As a second-line hormonal therapy for men, orchiectomy or a luteinizing hormone-releasing hormone agonist with or without an antiandrogen are reasonable alternatives. There are no reports regarding the use of the antiestrogen fulvestrant in men, but its mechanism of action and efficacy in women suggest that it will be a useful agent in hormone receptor-positive male breast cancer. For men with hormone-resistant disease, palliative chemotherapy with the same agents used for treatment of women with breast cancer is appropriate.
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PMID:Male breast cancer. 1259 42

Aromatase inhibitors are proving to be more effective than tamoxifen for postmenopausal patients with breast cancer. Estrogen concentrations in the breast are similar in both premenopausal and postmenopausal women, and several fold higher than circulating levels in postmenopausal women. In order to investigate the importance of intratumoral aromatase in stimulating the proliferation of the tumor, we used immunocytochemistry to determine the extent of aromatase expression in relationship to the response of the patient to aromatase inhibitor treatment. The relationship between positive staining for aromatase in the primary tumor and response to treatment with an aromatase inhibitor was investigated in a retrospective study of 102 patients with advanced breast cancer. Immunohistochemical staining using a monoclonal antibody against aromatase was performed on paraffin embedded tumor tissue. Response was evaluated using UICC criteria. Nine out of 13 patients with objective response to treatment stained positive and 49 of 89 patients with stable or progressive disease stained positive. No significant relationship between positive staining and objective response to treatment could be found. When patients with 'clinical benefit' (i.e. objective response plus prolonged stable disease of at least 6 months) were considered, also no relationship could be found. Further analysis of subgroups with positive hormone receptors, treatment with newer generation aromatase inhibitors, single metastatic site, non-visceral metastases and previous treatment only with tamoxifen did not show any relationship. Tumor aromatase expression did not correlate with response of patients with advanced breast cancer to aromatase inhibitor treatment. Most patients had relapsed from other treatments before receiving an aromatase inhibitor. It seems likely that many of these patients had tumors that may have progressed to hormone independence at this stage of the disease. Research in patients who have received treatment with aromatase inhibitors in earlier stages of disease (first line and adjuvant treatment) may provide further information on the relationship between tumor aromatase, steroid receptors and response to inhibitor treatment.
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PMID:The relationship between aromatase in primary breast tumors and response to treatment with aromatase inhibitors in advanced disease. 1467 35

Women with early breast cancer are exposed to an ongoing risk of relapse, even after successful surgical resection of the primary tumor and, where given, radiotherapy. Adjuvant chemotherapy and/or endocrine therapy can further help to prevent relapses by targeting metastatic disease deposits, which may be present but clinically undetectable. The benefits of adjuvant therapy are well documented, and millions of relapses have undoubtedly been prevented by treatment in this setting. Adjuvant tamoxifen has proven particularly effective in preventing relapses in hormone-receptor-positive (HR+) disease, and has been the standard treatment for affected women for over 30 years. However, long-term exposure to tamoxifen is associated with an unfavorable risk: benefit profile due to decreasing efficacy and an increasing incidence of harmful side effects. Although the risk of relapse is highest during the first 2-3 years after surgery, a residual risk remains indefinitely for those women who do not experience disease relapse in these early years, and the majority of all breast cancer recurrences and deaths occur after completion of 5 years of adjuvant tamoxifen. Hence, there is a great need for additional adjuvant therapies to reduce the considerable risk of late relapses in patients with HR+ disease: until recently no agent had been shown to provide a significant benefit over no further treatment. In 2003, upon publication of the first interim analysis of the MA.17 trial, letrozole became the first agent to be shown to significantly reduce relapses in women with HR+ early breast cancer who had completed 5 years of adjuvant tamoxifen. Subsequent analyses confirmed that letrozole significantly reduced recurrences, including distant metastases, and, in patients with node-positive disease, the agent also significantly improved overall survival, with the benefit of letrozole increasing with duration of therapy, at least up to 48 months. Preliminary results from a small, open-label study suggest that extended anastrozole therapy can also improve outcomes after completion of standard adjuvant tamoxifen. Ongoing analyses from MA.17, investigating how estrogen and progesterone receptor status and the length of time since finishing tamoxifen influence the effectiveness of letrozole, and studies evaluating the safety and efficacy of 10 years of extended aromatase inhibitor therapy, will help to optimize extended adjuvant therapy and improve outcomes for women with HR+ early breast cancer.
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PMID:Reducing the risk of late recurrence in hormone-responsive breast cancer. 1789 Feb 10

Many patients with a history of breast cancer (BC) will suffer from vasomotor symptoms, which can be induced or exacerbated by treatment with tamoxifen or aromatase inhibitors. The LIBERATE trial was designed as a randomized, double-blind, multicenter trial to demonstrate that tibolone 2.5mg/day (Livial) is non-inferior to placebo regarding BC recurrence in women with vasomotor symptoms surgically treated for primary BC within the last 5 years. Secondary objectives are effects on vasomotor symptoms as well as overall survival, bone mineral density and health-related quality of life. Mean age at randomization was 52.6 years, and the mean time since surgery was 2.1 years. The mean daily number of hot flushes and sweating episodes was 7.3 and 6.1, respectively. For the primary tumor, Stage IIA or higher was reported for >70% of the patients. In subjects whose receptor status was known, 78.2% of the tumors were estrogen receptors positive. At randomization, tamoxifen was given to 66.2% of all patients and aromatase inhibitors to 7%. Chemotherapy was reported by 5% at randomization. The adjuvant tamoxifen use in LIBERATE allows a comparison with the Stockholm trial (showing no risk of BC recurrence associated with hormone therapy), which was stopped prematurely subsequent to HABITS. The LIBERATE trial is the largest, ongoing, well-controlled study for treatment of vasomotor symptoms in BC patients.
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PMID:Safety of tibolone in the treatment of vasomotor symptoms in breast cancer patients--design and baseline data 'LIBERATE' trial. 1798 42

In early breast cancer, excision of the primary tumor, with or without radiotherapy and adjuvant chemotherapy or tamoxifen, is highly effective and yields long-term disease control for many patients. Some patients relapse early (within 2 years of surgery); such relapses are predominantly distant metastases and are associated with an increased risk for breast cancer-related mortality. The aromatase inhibitors (anastrozole, letrozole, and exemestane) have been shown to be superior to tamoxifen in improving disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Anastrozole and letrozole are approved in the initial adjuvant setting, and their use appears to be a better option than initial tamoxifen for preventing disease recurrence in the first 2 years of therapy, the peak time for recurrence and metastases. This review compares the ability of aromatase to prevent early recurrences, particularly distant metastases.
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PMID:Reducing early recurrence with adjuvant aromatase inhibitors: what is the evidence? 1849 Jan 63

Neoadjuvant (preoperative) systemic therapy is a good possibility for the treatment of symptomatic breast cancers of the locoregional stage. Chemotherapy or hormone therapy chosen according to the characteristics of the primary tumor, result in the regression of the tumor in the majority of the cases, favoring breast conserving surgery thereafter. The long-term effects of neoadjuvant systemic therapy are equivalent to that of adjuvant therapy, and the in vivo observed efficiency of the treatment reflects prognosis. Finally, systemic therapy introduced prior to surgery is not delayed by the possible adverse effects of the surgery. Detailed examination of the tumor and the patient is mandatory before starting systemic therapy. Besides breast imaging and histological examinations, staging is necessary. Pathological characterization of the tumor will enhance treatment choice based on the features of chemo- or hormone-sensitivity. For the treatment of chemosensitive tumors, taxane- and anthracycline-based polychemotherapy is the most efficacious. Data on neoadjuvant hormone therapy have been provided by studies on postmenopausal patients. Since the aromatase inhibitors are more efficient than tamoxifen, their use is the first option in this patient population. Among the molecular targeted agents, trastuzumab combined with chemotherapy produces extending therapeutic response rate. Following the completion of the neoadjuvant systemic therapy, breast imaging is required once more before performing breast and lymph node surgery. Postoperative radiotherapy is generally needed. The use of a common language and professional guidelines by the members of the multidisciplinary breast team is a condition for neoadjuvant systemic therapy.
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PMID:[Neoadjuvant systemic therapy in breast cancer]. 1910 57

The patient was an 86-year-old woman. In December 2005, she became aware of a tumor in her right breast at the nipple, gradually increasing in size and bleeding, and visited our department in April 2006. Roughly 3.5 cm in size, the tumor had a prominent large skin surface, bled profusely, and a dark red-colored was found at the E area of the right breast. Ultrasonography and mammography revealed that the tumor had invaded the skin and pectoralis major muscle (T4b). Core needle biopsy examination indicated invasive breast cancer (pap-tub), ER(+), PgR(+), HER2(3+). Chest CT scan and bone scintigraphy revealed swollen changes at the right axillary lymph nodes and osteoblastic changes in the 7th thoracic vertebra. We started anastrozole 1mg/day treatment. Tumor blood loss after one month was confirmed. After six months, the primary tumor size was reduced to 2 cm and the axillary lymph nodes disappeared. Administration continued about three years, and the tumor showed only the scar-like changes, and was unclear from ultrasonography (cPR). We report the long-term effect of aromatase inhibitor for elderly breast cancer patients without operation.
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PMID:[An elderly advanced breast cancer with a good response to anastrozole]. 2071 86


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