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

To avoid the complication of osteoporosis, hormone replacement therapy (HRT) is now standard therapy in women with premature ovarian failure. The indications for HRT after the age of 50 are more controversial. There are strong indications from case-control studies that in N. America and Europe HRT protects against osteoporotic fracture, myocardial infarction and stroke; yet the evidence from case control studies is insufficiently precise to quantitate accurately the potential benefits that would accrue from its more widespread use. Clear guidelines also need to be established on the potential usefulness of selective prescribing of HRT using one or more screening procedures. The only effective way of achieving this and of quantitating the potential benefits of HRT with sufficient accuracy is by means of one or more randomized controlled trials. Future research will also address concerns such as the possible increase in the risk of breast cancer after 10 or more years of therapy. Critical to the more widespread acceptance of HRT may be the development of safe regimes which do not promote uterine bleeding as well as minimizing other unwanted side-effects.
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PMID:Future prospects for hormone replacement therapy. 145 Aug 79

Adjuvant chemotherapy, which is known to be a cause of premature ovarian failure, is now recommended for most women diagnosed with breast cancer, and it has been postulated that the effects of chemotherapy are of the same order as those of ovarian ablation. Thus, it is important to correlate disease-free survival with induction of early menopause. We examined the literature for papers reporting the effects of chemotherapy on menstruation and ovarian changes in premenopausal women. Few studies reported such effects, but of those papers reviewed here, no such benefits in terms of disease-free survival were found. Thus, the benefits of adjuvant chemotherapy must be carefully weighed against the risk of early menopause in premenopausal women with good prognosis breast cancer.
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PMID:Amenorrhea following chemotherapy for breast cancer: effect on disease-free survival. 788 12

Issues of long-term toxicity from treatment for breast cancer, including the induction of premature ovarian failure, appear to be of increasing importance for breast cancer survivors. The incidence of treatment-related amenorrhea is related to patient age and to the treatment regimen. Whereas the induction of ovarian failure may be advantageous with respect to breast cancer outcome, it is not clear that there is any advantage to permanent menopause over reversible hormonal manipulations. In addition, menopause may be associated with a variety of adverse health effects. Although nonhormonal therapies are available to manage many of the consequences of menopause, avoidance of chemotherapy-related ovarian toxicity may provide the best prospects for fertility after treatment. Pregnancy after breast cancer is a realistic consideration for some breast cancer survivors and is not clearly detrimental to either the mother or her offspring.
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PMID:Fertility and the impact of systemic therapy on hormonal status following treatment for breast cancer. 1112 97

Inherited BRCA2 mutations predispose individuals to breast cancer and increase risk at other sites. Recent studies have suggested a role for the APC I1307K allele as a low-penetrance breast cancer susceptibility gene that enhances the phenotypic effects of BRCA1 and BRCA2 mutations. To model the consequences of inheriting mutant alleles of the BRCA2 and APC tumor suppressor genes, we examined tumor outcome in C57BL/6 mice with mutations in the Brca2 and Apc genes. We hypothesized that if the Brca2 and Apc genes were interacting to influence mammary tumor susceptibility, then mammary tumor incidence and/or multiplicity would be altered in mice that had inherited mutations in both genes. Female and male offspring treated with a single IP injection of 50 mg/kg N-ethyl-N-nitrosourea (ENU) at 35 days of age developed mammary adenoacanthomas by 100 days of age. The female Apc-mutant and Brca2/Apc double-mutant progeny had mean mammary tumor multiplicities of 6.7+/-2.8 and 7.2+/-2.7, respectively, compared to wild-type and Brca2-mutant females, which had mean mammary tumor multiplicities of 0.1+/-0.4 and 0.3+/-0.5, respectively. Female ENU-treated Apc-mutant and Brca2/Apc double heterozygotes were also susceptible to premature ovarian failure. Thus, the inheritance of an Apc mutation predisposes ENU-treated female and male mice to mammary tumors and, in the case of female mice, to ovarian failure. These results indicate that mammary tumor development in Apc-mutant mice can progress independently of ovarian hormones. The Apc mutation-driven phenotypes were not modified by mutation of Brca2, perhaps because Brca2 acts in a hormonally dependent pathway of mammary carcinogenesis.
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PMID:Mammary tumor induction and premature ovarian failure in ApcMin mice are not enhanced by Brca2 deficiency. 1121 75

Osteoporosis is a disease that causes substantial morbidity and mortality for which preventive therapy is available. Women with breast cancer are at increased risk for osteoporosis for several reasons, including premature ovarian failure as a result of treatment, direct effects of chemotherapy, and effects of the breast cancer itself. As the incidence of breast cancer continues to increase and survival rates continue to improve, the importance of appropriate screening for and management of osteoporosis becomes more apparent. This article reviews the evidence supporting an increased risk for development of osteoporosis in women with breast cancer and summarizes strategies for prevention and treatment of osteoporosis in this population.
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PMID:Osteoporosis in women with breast cancer. 1249 50

Chronically elevated luteinizing hormone (LH) induces significant pathology in the LHbetaCTP transgenic mouse model, which uses the bovine gonadotropin alpha (alpha)-subunit promoter to direct transgene expression specifically to gonadotropes in the anterior pituitary. Previously, it was shown that female LHbetaCTP mice are infertile due to anovulation, develop granulosa cell tumors, and undergo precocious puberty from elevated LH and steroid hormones that fail to completely repress the alpha-subunit promoter. This chapter will discuss recent studies that further elucidate the impact of chronically elevated LH on diverse physiological systems. Granulosa cell tumors induced by elevated LH are strain dependent and prevented when transgenics are treated with human chorionic gonadotropin (hCG) surges. A granulosa cell tumor-associated transcriptome is generated, revealing several possible gene candidates for ovarian granulosa cell tumorigenesis. Primordial follicles in LHbetaCTP transgenics become depleted and oocytes exhibit increased rates of meiotic segregation defects, although meiotic competency is acquired normally. Anovulation can be rescued in transgenics by superovulation, though pregnancy fails at midgestation due to maternal factors. Uterine receptivity defects prevent implantation of normal embryos following induction of pseuodpregnancy. Transgenics develop Cushing-like adrenocortical hyperfunction with increased corticosterone production following induction of adrenal LH receptor expression. Elevated LH acts as a tumor promoter in the gonads and the adrenal gland, when expressed in conjunction with the inhibin-alpha SV40 transgene. Finally, chronic elevated LH promotes mammary tumorigenesis. The understanding of multiple clinical pathologies--including ovarian cancer, perimenopausal reproductive aging, premature ovarian failure, polycystic ovarian syndrome, Cushing's syndrome, and breast cancer--may be enhanced through further study of this useful transgenic mouse model.
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PMID:Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology. 1279 27

Thanks to improvements in treatment regimens, more and more patients are now surviving cancer. However, cancer survivors are faced with the serious long-term effects of the different modalities of cancer treatments. One of these adverse effects is chemotherapy-induced irreversible damage to the ovarian tissues, which leads to premature ovarian failure and its resulting consequences such as hot flashes, osteoporosis, sexual dysfunction and the risk of infertility. Chemotherapy-induced ovarian failure (or chemotherapy-induced premature menopause) affects the quality of life of female cancer survivors. Although there is no clear definition of chemotherapy-induced ovarian failure, irreversible amenorrhoea lasting for several months (>12 months) following chemotherapy and a follicle stimulating hormone level of > or = 30 MIU/mL in the presence of a negative pregnancy test seems to be an appropriate characterisation. Different chemotherapy agents, alkylating cytotoxics in particular, have the potential to cause progressive and irreversible damage to the ovaries. The result of this damage is a state of premature ovarian failure, with progressive declining of estrogen levels, decreasing bone mass and an increased risk of fractures. Historically, hormonal replacement therapy (HRT) has been used to treat menopausal problems in the general population, but concerns about the potential of estrogen to increase the risk of breast cancer in women at high-risk or increase the risk of recurrence in cancer survivors, have forced physicians to utilise alternative treatments. This review discusses some of the newer therapies that are now available to provide appropriate symptom control, avoid complications such as fractures and possibly prevent infertility by making the ovarian epithelium less susceptible to cytotoxic agents.
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PMID:Chemotherapy-induced ovarian failure: manifestations and management. 1585 42

Menopausal age is important as a retrospective marker for ovarian senescence, an early menopausal age is associated with an increased risk of cardiovascular diseases and osteoporosis, whereas a later menopausal age has been associated with an increased risk of breast cancer. The worldwide average for age at natural menopause is approximately 51 years and is more or less normally distributed with a range roughly between 40 and 60 years. Environmental factors explain only a small part of the variance and it has been proposed that genetic factors are the main source of variation. Menopausal age may be considered a continuous complex trait. Complex traits are defined as traits that are influenced by both multiple genetic and environmental factors. A category of complex traits comprises those that are measured on a continuous scale. The genomic loci that make up the genetic component are called 'quantitative trait loci' or QTLs. The first linkage study on menopausal age suggests that the involvement of the X-chromosome may not be limited to premature ovarian failure (POF), but may influence the broader spectrum of menopausal age. A potentially new locus for variation in menopausal age was allocated to chromosome 9. Further studies need to identify new candidate genes to help unravel the pathophysiology of menopausal age. It is becoming increasingly clear that, in any speciality, it should be acknowledged that genetic factors are involved in many traits and that uncovering these factors may provide insight into pathogenesis and ultimately advance prevention and treatment of disease. In this review we discuss methods and basic principles of gene finding for such traits, exemplified by menopausal age as phenotype. Furthermore, we give an overview of the state of the art of candidate gene studies and linkage studies.
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PMID:Genetic studies to identify genes underlying menopausal age. 1602 48

Breast cancer accounts for one third of all neoplasms seen in reproductive-age women and affects tens of thousands of women each year in that age group. The adjuvant chemotherapy regimens used for the treatment commonly affect fertility and cause premature ovarian failure. There have been recent advances in the field of fertility preservation, which can allow many of these breast cancer survivors to have children in the future. The most established option is embryo cryopreservation; oocyte cryopreservation can be considered in single women. Both of these approaches require approximately 2 weeks of ovarian stimulation beginning with the onset of the patient's menstrual cycle. Thus, it is crucial that these patients are referred to appropriate assisted reproduction centers as soon as they are diagnosed with breast cancer. Recently developed ovarian stimulation protocols using tamoxifen and letrozole can be used to increase the margin of safety in these patients. When and if a breast cancer patient does not have time to undergo ovarian stimulation prior to chemotherapy, ovarian cryopreservation for future autotransplantation can be offered as the last resort. The benefit of ovarian protection by gonadotropin-releasing hormone analogues is unproven and unlikely, and thus this treatment should not be offered as the sole method of fertility preservation.
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PMID:Fertility preservation in young women undergoing breast cancer therapy. 1672 Aug 42

There has been some confusion among women and health professionals since the publication of the Women's Health Initiative and Million Women studies about the management of premature ovarian failure (POF). Both studies were undertaken in women aged 50 and over, and cannot be extrapolated to their younger counterparts, who would normally be producing their endogenous estrogen, since they have functioning ovaries. Estrogen-based replacement therapy is the main stay of treatment for women with POF and is recommended at least until the average age of natural menopause (52 years in the UK). This view is endorsed by regulatory bodies such as the Committee on Safety of Medicines (now the Commission on Human Medicines) in the UK. No evidence shows that estrogen replacement increases the risk of breast cancer to a level greater than that found in normally menstruating women, and women with POF do not need to start mammographic screening early unless other risk factors are present, such as family history.
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PMID:Management of premature menopause. 1744 68


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