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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We herein report 1 case in which hormone therapy and neoadjuvant chemotherapy by local intraarterial infusion were conducted for locally advanced breast cancer, and were revealed to be useful in terms of local control. Administration of doxifluridine (5'-DFUR: Furtulon) (1,200 mg/day, 5 day continuous dosing followed by 2 day washout) and medroxyprogesterone acetate (MPA: Hysron H) (1,200 mg/day) was followed by chemotherapy consisting of intraarterial infusion of 100 mg of docetaxel (TXT: Taxotere), once monthly, via the left internal thoracic artery and left lateral thoracic artery. As a result, marked shrinkage of tumors was confirmed. Under these circumstances, left standard radical mastectomy plus skin grafting were performed. While under treatment, no serious adverse events were observed, and the patient made satisfactory progress after surgical procedure. She thus left hospital in a positive frame of mind.
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PMID:[One case of locally advanced breast cancer in which multidisciplinary treatment, chiefly, therapy with preoperative intraarterial infusion of docetaxel (TXT), was successful]. 1214 5

The bulk of the experimental data suggest beneficial effects of estrogen (both premenopausal use of OCs and postmenopausal use of ERT-HRT). An intriguing finding from the monkey studies is that social subordination, which induces estrogen deficiency in female monkeys, accelerates atherosclerosis premenopausally and predicts extent of postmenopausal atherosclerosis. This effect can be inhibited by exogenous estrogen, premenopausally. The results suggest that more effort on detecting and regulating premenopausal ovarian dysfunction may be justified. A complication in understanding estrogen action may be the result of varying extents of arterial damage. For example, primary prevention studies in both postmenopausal animals and women have provided strong evidence of atheroprotection with a variety of estrogens. In contrast, the results of secondary prevention studies [10,12] have in general suggested little cardioprotection with either ERT or HRT. Studies in rabbits suggest the antiatherogenic effect of estrogen may not be present when the endothelium is damaged [64]. The state of the endothelium may be critical for some estrogen actions. For those effects of estrogen that require the ER, be it ERalpha or ERbeta, the presence of the receptor may vary with age, disease state, or type of hormone therapy. If continuous combined HRT therapy decreases ER in the artery as it does in the uterus, this may eliminate those estrogen actions requiring the ER, but not others. Older women who have not been exposed to estrogens for many years may be more sensitive to some estrogen effects, and may need lower doses of ERT-HRT. Recent reports suggest that lower doses of estrogens maintain beneficial effects on lipoproteins and coagulation factors [95], while also requiring lower doses of progestogens to protect the uterus [96]. These beneficial findings are very promising in light of the improvements in CHD risk and decreased stroke risk reported with low-dose estrogens [5]. It ill be interesting to see if CRP is increased with lower doses of estrogens and whether these changes are associated with increased early risk of CHD. Perhaps older women with CHD are also more obese, may have diabetes, and may be more susceptible to inflammatory and thrombotic effects of higher doses of estrogens. There are many questions left unanswered. It is hoped that some of the answers may come from the WHI, which is a large prospective trial assessing ERT and HRT. The age range is also relatively large and may be able to determine if older women respond differently than younger women. Some initial data from the WHI have been made available suggesting a small increased risk in the first 2 years and a trend for decreasing risk in the last months of the first 2 years [34]. Just recently, the CEE + MPA arm of the study was stopped early by the data and-safety monitoring board as the overall health risks exceeded benefits with increases in both breast cancer and CVD [97]. The remainder of the study groups including an estrogen-only arm, are expected to continue until 2005.
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PMID:Reproductive hormones and cardiovascular disease mechanism of action and clinical implications. 1235 69

We have developed four new mammary adenocarcinoma cell lines from the C3(1)/SV40 Large T-antigen (Tag) transgenic mouse model: M28N2 and M27H4 (weakly tumorigenic), M6 (carcinoma), and M6C (metastatic). The C3(1) promoter directs Tag expression to the mammary epithelium and 100% of female C3(1)/Tag transgenic mice develop mammary adenocarcinoma in a predictable and progressive manner. The cell lines we developed from this model are demonstrated to be of epithelial origin and display growth rates, both in vitro and following subcutaneous inoculation into nude mice, that are consistent with their representative stage of tumor progression. The more tumorigenic cell lines, M6 and M6C, both express the sodium/iodide symporter, a mammary carcinoma cell marker with potential therapeutic and diagnostic applications. All of the cell lines express estrogen receptor (ER) alpha and ER beta mRNA, and Western blot analysis demonstrates that the ER alpha protein is down-regulated in the M6 and M6C cell lines. M28N2 cells also express progesterone receptor (PgR), which is very unusual in a mouse mammary carcinoma cell line. In addition, all of the cell lines display growth inhibition when plated in media supplemented with charcoal-stripped fetal calf serum (CS FBS). When CS FBS is supplemented with beta estradiol or the progestin MPA, no significant difference in growth rates is observed relative to growth in CS FBS. The development and characterization of a progressive series of new mammary carcinoma cell lines will aid in the study of mammary carcinoma progression both in vitro and in vivo.
Breast Cancer Res Treat 2003 Jan
PMID:Development and characterization of a progressive series of mammary adenocarcinoma cell lines derived from the C3(1)/SV40 Large T-antigen transgenic mouse model. 1260 5

The Women's Health Initiative (WHI) a double-blind, placebo-controlled trial studying the effects of continuous combined estrogen-progestin regimen (CEE 0.625 mg plus 2.5 mg MPA daily), was stopped prematurely on the basis of a slight increase in the risk of invasive breast cancer, myocardial infarction and stroke. The study was not planned to examine other important aspects of HRT treatment, such as menopausal symptoms and quality of life, since the CEE only arm of the study was not terminated, it is possible that the specific drug tested in the study had different effects on outcome than other preparations available in the market. One should remember that many previous observational studies actually demonstrated cardiovascular benefits in women using other types or regimens of hormones. There seems to be a consensus on the interpretation of the WHI trial: 1) hormones are the best treatment for symptomatic women since there are no real alternatives; 2) women who use HRT for more than 5 years should discuss the latest data with their physician, in order to consider their individual risk-benefit equation; 3) it is logical to prefer hormones, which are different from CEE plus MPA daily.
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PMID:[Lessons from the Women's Health Initiative (WHI) using hormone replacement therapy with regard to heart disease--the dream that has been broken?]. 1269 64

Hormone replacement therapy (HRT) is effective for relieving vasomotor symptoms such as hot flash and vaginal atrophy and for preventing bone loss in postmenopausal and bilaterally ovariectomized women. However, compliance with HRT was reported to be low despite the benefits of HRT. In addition, results of several recent large-scale randomized clinical trials have demonstrated that protection from cardiovascular disease is not an indication for treatment with estrogen and progestin in postmenopausal women. Recent studies have demonstrated that low-dose HRT is safe and effective for prevention of postmenopausal bone loss. Low-dose HRT has also been shown to be effective for reducing the number and severity of hot flashes, improving vaginal atrophy, and inducing favorable changes in lipids, lipoproteins and hemostatic factors. Moreover, low-dose regimens of CEE (conjugated equine estrogen) and MPA (medroxyprogesterone acetate) result in higher rates of amenorrhea and endometrial protection compared with the conventional dose of HRT. Low-dose HRT may improve the compliance rate and may be more effective than conventional-dose HRT for reducing the risk of breast cancer. On the other hand, it has been shown that transdermal estrogen treatment reduces the incidence and severity of hot flashes and that long-term treatment with transdermally administered estrogen is effective for protection against osteoporosis. Transdermal administration of estrogen is recommended in postmenopausal women with hypertriglycemia because this treatment has little effect on lipid metabolism. The serum estradiol level was reported to be closely related to estrogenic effects on various tissues. An HRT regimen should be based on the needs of each patient. Serum estradiol levels in women should be maintained at appropriate levels for benefits and not be excessively high in order to prevent side effects. Selection of the most appropriate regimen of HRT (dose, route of administration and schedule) for the needs of the individual are important factors to increase the rate of continuation with HRT.
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PMID:Hormone replacement therapy in postmenopausal women. 1367 82

Whether progestins protect against the risk of breast cancer or enhance that risk has been a major area of controversy over the past several years. Observational studies have reported conflicting results and experimental studies examining whether progestins exert mitogenic or anti-mitogenic actions on breast tissue report divergent results. Based upon a wide range of animal, epidemiologic and clinical data, most investigators agree that estrogens contribute to the development of breast neoplasms. However, the additional effect of progestins on this risk has been the subject of substantial discussion and controversy. A variety of experiments have been carried out using human breast cancer cells grown in vitro and as xenografts in nude mice. These studies demonstrated both mitogenic and anti-mitogenic effects depending upon the precise experimental conditions. Two potential reasons for these differences include differential metabolism of progestins into inhibitory pregnenes or stimulatory 5-alpha-reduced pregnanes or the presence of a protein (GPR 30) which allows the anti-mitogenic effects of progestins to be manifest. Based upon the conflicting nature of the results in experimental studies, we believe that only data in patients provide substantial insight into the actions of progestins on the intact human breast. Studies have now demonstrated that cell proliferation and breast density is higher during the luteal than during the follicular phase of the menstrual cycle. In postmenopausal women, long-term exposure to estrogen plus a progestin results in a marked enhancement of proliferation of the terminal duct lobular units as well as in breast density. These data, taken together, provide substantial evidence that progestins are mitogenic on the human breast when given long term to postmenopausal women. To critically evaluate the observational studies regarding breast cancer risk from progestins, we developed a set of stringent criteria for acceptance of individual studies. Four of the five studies meeting these criteria reported a greater risk of breast cancer with combination estrogen/progestin regimens than with estrogen alone. More importantly, the first randomized, prospective, controlled trial of the risk of breast cancer with an estrogen/progestin combination (the Women's Health Initiative Study) has now been published. This study reported a 26% increased relative risk of breast cancer with the estrogen/progestin combination. Based upon these data, we believe that progestins do add to the risk of breast cancer over and above that imparted by estrogen alone. The attributable risk during use for 5 years or less is small but increases logarithmically during long-term use. The majority of data regarding progestins are derived from regimens using MPA. However, we conclude from our analysis that the burden of proof regarding progestins has now shifted. One must now prove that an estrogen/progestin combination is safe with respect to breast cancer rather than having to prove it harmful.
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PMID:Risk of breast cancer with progestins: critical assessment of current data. 1466 88

The patient is a 42-year-old woman who had advanced (Stage IV) right breast cancer with contralateral supraclavicular lymph node metastasis. She was treated with the combined use of MPA and the intra-arterial infusion chemotherapy. We administered EPI into the left subclavian artery and the right internal thoracic artery. Total dose of EPI was 210 mg. MPA was administered po at 1,200 mg/day daily. During the chemotherapy, she experienced only grade 2 alopecia. After the chemotherapy, the regressive change was noted in the primary lesion. The clinical response was evaluated CR. She underwent right modified mastectomy and the resection of contralateral supraclavicular lymph nodes. Although the clinical response was very good, the pathological effect was only Grade 1b. Eight years have passed since the operation, and the patient is still alive with no sign of recurrence. It is suggested that this combination therapy may be useful for advanced breast cancer and the like.
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PMID:[A long-surviving patient with Stage IV breast cancer with no recurrence after combined therapy of medroxy progesterone acetate (MPA) and intra-arterial infusion chemotherapy]. 1544 62

A 75-year-old woman with low back pain had attended a local orthopedic clinic since around December 1990, but no remission had been achieved. The patient also had a gait disturbance, and visited our hospital for detailed examinations in May 1992. Bone scintigraphy revealed metastatic tumors of L 1 and L 2. Histopathological findings and tumor marker measurements led to a diagnosis of primary breast cancer. The patient was treated with TAM (20 mg/day) and 5-FU (150 mg/day). The tumor marker levels showed repeated cycles of slight increases and decreases. Acute elevations of the tumor markers occurring on January 24, 1997, and January 5, 2001, were successfully treated with MPA (800 mg/day) and 5'-DFUR (600 mg/day), but continuous administration of these drugs was difficult because of their adverse effects. A significant increase in the tumor marker levels (CA15-3 600 U/ml, CEA 197 ng/ml) was again observed on December 2, 2003. The patient showed no favorable response to the combination of MPA and 5'-DFUR but had persistent back pain. Exemestane given at 25 mg/day markedly improved both clinical symptoms and tumor marker levels. The results indicate that exemestane would be an effective hormone therapy for metastatic breast cancer.
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PMID:[Effective reduction of elevated tumor markers by exemestane--a 12-year follow-up of a case of bone metastatic breast cancer]. 1579 20

Many mammary tumors express estrogen receptors (ER) and progesterone receptors (PR), and there is increasing evidence that progestins influence gene expression of breast tumor cells. To analyse the impact of progestins on breast cancer cells, we compared (a) the expression of two cytokines, involved in tumor progression, and searched (b) for differentially regulated genes by a microarray, containing 2400 genes, on T47D breast cancer cells cultured for 6 days with 17beta-estradiol (E2) or E2+medroxyprogesterone acetate (E2+MPA). Lower amounts of PDGF and TNFalpha were found in culture supernatants of E2+MPA treated T47D cells. MPA addition induced a 2.8-3.5-fold increase of the mRNA expression of (a) tristetraprolin, which is involved in the posttranscriptional regulation of cytokine biosynthesis, and (b) zinc-alpha2-glycoprotein and Na, K-ATPase alpha1-subunit, which both resemble differentiation markers of breast epithelium. In contrast, the mRNA expression of lipocalin 2, which promotes matrixmetalloproteinase-9 activity, was decreased five-fold in E2+MPA treated cells. Our data show that the expression of genes from various functional gene families is regulated differentially by E2 and E2+MPA treatment in T47D cells. This suggests that exogenous progestins applied for therapy and endogenous changes of the progesterone levels during the menstrual cycle both influence breast cancer pathophysiology.
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PMID:Estradiol and medroxyprogesterone acetate regulated genes in T47D breast cancer cells. 1586 26

Progesterone in hormone replacement therapy (HRT) preparations increases, while hysterectomy greatly reduces, the incidence of breast cancer. Cross-talk between the progesterone and growth factor signaling pathways occurs at multiple levels and this maybe a key factor in breast cancer survival and progression. To test this hypothesis, we characterized the effect of progesterone pre-treatment on the sensitization of the epidermal growth factor (EGF) signaling pathway to EGF in the breast cancer cell line ZR-75. For the first time in ZR-75 cells and in agreement with previous work using synthetic progestins, we demonstrate that pre-treatment with the natural ligand progesterone increases EGF receptor (EGFR) levels and subsequent ligand-dependent phosphorylation. Downstream we demonstrate that progesterone alone increases erk-1 + 2 phosphorylation, potentiates EGF-phosphorylated erk-1 + 2 and maintains these levels elevated for 24 h; over 20 h longer than in vehicle treated cells. Additionally, progesterone increased the levels of STAT5, another component of the EGF signaling cascade. Progesterone increased EGF mediated transcription of a c-fos promoter reporter and the nuclear localization of the native c-fos protein. Furthermore, progesterone and EGF both alone and in combination, significantly increase cell proliferation. Several results presented herein demonstrate the conformity between the action of the natural ligand progesterone with that of synthetic progestins such as MPA and R5020 and allows the postulation that the progestin/progesterone-dependent increase of EGF signaling provides a survival advantage to burgeoning cancer cells and may contribute to the breast cancer risk associated with endogenous progesterone and with progestin-containing HRT.
Breast Cancer Res Treat 2005 Nov
PMID:Progesterone pre-treatment potentiates EGF pathway signaling in the breast cancer cell line ZR-75. 1617 15


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