Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This editorial consists of summaries of the discussions on incidence, pathogenesis, prognosis and patient follow-up, and transcripts of the discussions on detection and treatment of endometrial carcinoma, from a symposium held in Carefree, Arizona. 75% of the cancers occur in postmenopausal women; average age is 52 years, but is decreasing. Endometrial carcinoma rose from 20.3 to 46.3% of all uterine cancers in Cleveland University Hospitals from 1941-1970. Older patients are often diabetic, overweight, nulliparous, with anovulatory or familial history; young women frequently resemble mild Stein-Levinthal syndrome. Clinically, 20% of patients are assymptomatic, others may have softer or larger uterus, larger ovaries, irregular postmenopausal bleeding, or lengthy onset of menopause. The Gravlee jet wash is indicated for high risk patients and those about to take estrogen. Endometrial carcinoma first affects epithelium, then endometrial stroma, then upper myometrium, lower myometrium, then other organs, perhaps via lymphatics, vagina, tubes, but ascites is uncommon. Generally, U.S. physicians use intrauterine radium followed by surgery, British use surgery first, and Swedish use radiation only. Cases must be treated individually, e.g. surgery only for minimal cancer, radium and surgery for more serious cases, and preoperative external radiation also for advanced disease. Although radiation lessens chance of implantation during surgical trauma, insertion of intrauterine radium enhances spread of tumor cells. Injectable progestins sometimes control metastatic disease, although they require 8 weeks to act. Progestins may help those with late recurrence, squamous metaplasia, or who are under 50 years of age. Estrogens are rarely effective. Prognois for terminal patients often includes subjective improvement, bowel obstruction, lung complications, hemorrhage. Radiation side effects and menopausal symptoms are often problems for cured patients. In young cured patients the endometrium should be suppressed with progestins or oral contraceptives.
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PMID:Endometrial cancer: rising incidence, detection and treatment. 469 33

Phytoestrogens are a group of plant-derived substances that are structurally or functionally similar to estradiol. There has been much interest in the potential role of phytoestrogens in cancer prevention and treatment of estrogen-deficient states. This review summarizes the evidence for phytoestrogen risks and benefits relevant to the breast cancer survivor, including prevention of a second primary breast cancer or metastatic disease, reduction in menopausal symptoms, and interactions with tamoxifen. Epidemiological data suggest a breast cancer protective role for phytoestrogens, and there is some supporting clinical data, but they are far from conclusive. In addition, there is some evidence that genistein, the most prevalent isoflavone in soy, can stimulate estrogen receptor-positive (ER+) breast cancer growth and interfere with the antitumor activity of tamoxifen at low levels. Given current knowledge, women who have ER+ tumors should not increase their phytoestrogen intake. Several studies suggest an inhibitory effect on ER- breast cancer cell growth, and it may be reasonable for women with ER- tumors to safely consume soy and possibly other phytoestrogens. However, the optimal amount and source are not clear. More research is needed to clarify the role of phytoestrogens in breast cancer prevention and in treating estrogen-deficient diseases in women who have had breast cancer.
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PMID:Phytoestrogens: potential benefits and implications for breast cancer survivors. 1458 3

Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Women<40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age<40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC<40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient's comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in presence of visceral metastases, unless there is concern or proof of endocrine resistance or there is a need for rapid disease response and/or symptom control. Recommendations for chemotherapy (CT) should not differ from those for older patients with the same characteristics of the metastatic disease and its extent. Young age by itself should not be an indication to prescribe more intensive and combination CT regimens over the sequential use of monotherapy. Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) represent an important group of promising drugs in managing patients with breast cancer susceptibility gene (BRCA)-1- or BRCA-2-associated BC. Specific age-related side effects of systemic treatment (e.g., menopausal symptoms, change in body image, bone morbidity, cognitive function impairment, fertility damage, sexual dysfunction) and the social impact of diagnosis and treatment (job discrimination, taking care for children) should also be carefully addressed when planning systemic long-lasting therapy, such as endocrine therapy. Survivorship concerns for young women are different compared to older women, including issues of fertility, preservation, and pregnancy.
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PMID:Breast cancer under age 40: a different approach. 2579 77

Breast cancer is the most prevalent cancer in women, causing a significant mortality worldwide. Different endocrine strategies are available for the treatment of hormone-sensitive breast cancer, including antiestrogen tamoxifen and fulvestrant, as well as third-generation aromatase inhibitors (AIs), such as letrozole, anastrozole, and exemestane. In this review, we will focus on exemestane, its clinical use, and its side effects. Exemestane is a steroidal third-generation AI now used in all treatment settings for breast cancer. In the metastatic disease, it has been extensively investigated as the first-, second-, and further-line treatment and it is now registered for the treatment of postmenopausal women with advanced estrogen-receptor-positive breast cancer whose disease has progressed following antiestrogen therapy. A potential lack of cross-resistance with nonsteroidal AIs has been described, giving additional therapeutic opportunities in sequences of endocrine agents. Exemestane is also approved for the adjuvant treatment of postmenopausal early breast cancer, either as upfront monotherapy for 5 years, as a switch following 2-3 years of tamoxifen, or as extended therapy beyond 5 years of adjuvant treatment. New promising data also showed a beneficial effect in young premenopausal early breast cancer patients, when administered together with ovarian suppression. Interesting results have also emerged when exemestane has been investigated as neodjuvant treatment as well as preventive agent in healthy women at high risk for breast cancer. Exemestane is generally well tolerated, with a side effect profile similar to that of other AIs, including menopausal symptoms, arthralgia, and bone loss. In conclusion, exemestane can be considered an effective and well-tolerated endocrine treatment option for all stages of breast cancer.
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PMID:Clinical utility of exemestane in the treatment of breast cancer. 2606 72

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 36-year-old premenopausal woman had been diagnosed with stage III breast cancer. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer, measuring 7 cm. The tumor had lobular histology and was considered grade 2 of 3. Metastatic carcinoma was identified in 10 of 13 axillary nodes. Immunohistochemical studies showed that the tumor was strongly positive for estrogen and progesterone receptor expression and had a Ki-67 score of 15% (> 20% is considered high according to a Swedish quality control study and the St Gallen Expert Consensus).(1,2) There was no amplification of the HER2/neu gene. Staging scans were negative for metastatic disease. In the adjuvant setting, she received three cycles of anthracycline-cyclophosphamide combination chemotherapy followed by three cycles of taxane chemotherapy and then locoregional radiotherapy. After completion of chemotherapy, she developed amenorrhea. As adjuvant endocrine therapy, she began monthly goserelin administration to achieve ovarian function suppression (OFS), in combination with the aromatase inhibitor (AI) exemestane. She experienced menopausal symptoms including hot flashes, vaginal dryness, and sexual dysfunction. After two monthly treatments with goserelin and exemestane, a sensitive assay for serum estradiol was checked and returned at 16 pg/mL (61 pmol/L); postmenopausal range for sensitive assay is less than 15 pg/mL (< 50 pmol/L). The patient has now been referred to our unit to discuss further management.
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PMID:Is Estradiol Monitoring Necessary in Women Receiving Ovarian Suppression for Breast Cancer? 2803 82

Background We analyzed long-term quality of life (QoL) and prognostic factors for QoL as well as clinical outcome in patients with advanced cervical cancer (ACC) treated with primary radiochemotherapy (RChT) consisting of external beam radiotherapy (EBRT) with or without sequential or simultaneous integrated boost (SIB) to the parametria, intracavitary brachytherapy and concomitant chemotherapy (ChT). Patients and methods Eighty-three women were treated with primary RChT between 2008 and 2014. Survival of all patients was calculated and prognostic factors for survival were assessed in univariate and multivariate analysis. In 31 patients QoL was assessed in median 3 years (range 2-8 years) after treatment. QoL was compared to published normative data and the influence of age, tumour stage, treatment and observed acute toxicities was analyzed. Results Thirty-six patients (43.4%) died, 18 (21.7%) had a local recurrence and 24 (28.9%) had a distant progression. Parametrial boost (p = 0.027) and ChT (p = 0.041) were independent prognostic factors for overall survival in multivariate analysis. Specifically, a parametrial equivalent doses in 2-Gy fractions (EQD2) > 50 Gy was associated with an improved overall survival (OS) (p = 0.020), but an EQD2 > 53 Gy did not further improve OS (p = 0.194). Tumour size was the only independent prognostic factor for local control (p = 0.034). Lymph node status (p = 0.038) and distant metastases other than in paraaortic lymph nodes (p = 0.002) were independent prognostic factors for distant progressionfree survival. QoL was generally inferior to the reference population. Age only correlated with menopausal symptoms (p = 0.003). The degree of acute gastrointestinal (p = 0.038) and genitourinary (p = 0.041) toxicities correlated with the extent of chronic symptom experience. Sexual/vaginal functioning was reduced in patients with larger tumours (p = 0.012). Parametrial EQD2 > 53 Gy correlated with reduced sexual/vaginal functioning (p = 0.009) and increased sexual worry (p = 0.009). Whether parametrial dose escalation was achieved by sequential boost or SIB, did not affect survival or QoL. Conclusions Primary RChT is an effective treatment, but long-term QoL is reduced. The degree of acute side effects of RChT correlates with the extent of chronic symptoms. Patients benefit from parametrial SIB or sequential boost, but an EQD2 > 53 Gy does not further improve survival and negatively affects QoL.
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PMID:Percutaneous parametrial dose escalation in women with advanced cervical cancer: feasibility and efficacy in relation to long-term quality of life. 3021 42