Successful treatment of accessory breast cancer with endocrine therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang CX
PROVIDER: S-EPMC5260479 | biostudies-literature | 2017 Jan.
REPOSITORIES: biostudies-literature
Publications
Successful treatment of accessory breast cancer with endocrine therapy.
Wang Chun-Xi CX Guo Shu-Li SL Han Li-Na LN
Journal of Zhejiang University. Science. B 20170101 1
Accessory breast cancers in males are extremely rare, and only a few cases have been reported in the literature. In this paper, an 87-year-old male patient was diagnosed with an accessory breast cancer by means of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and immunohistochemistry based on needle biopsy, and has undergone successful resection and postoperative adjuvant endocrine therapy. He was the oldest male patient wi ...[more]
Similar Datasets
Project description:Breast cancer, a hormone-dependent tumour, generally includes four molecular subtypes (luminal A, luminal B, HER2 enriched and triple-negative) based on oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2. Multiple hormones in the body regulate the development of breast cancer. Endocrine therapy is one of the primary treatments for hormone-receptor-positive breast cancer, but endocrine resistance is the primary clinical cause of treatment failure. Prolactin (PRL) is a protein hormone secreted by the pituitary gland, mainly promoting mammary gland growth, stimulating and maintaining lactation. Previous studies suggest that high PRL levels can increase the risk of invasive breast cancer in women. The expression levels of PRL and PRLR in breast cancer cells and breast cancer tissues are elevated in most ER+ and ER- tumours. PRL activates downstream signalling pathways and affects endocrine therapy resistance by combining with prolactin receptor (PRLR). In this review, we illustrated and summarized the correlations between endocrine therapy resistance in breast cancer and PRL, as well as the pathophysiological mechanisms and clinical practices. The study on PRL and its receptor would help explore reversing endocrine therapy-resistance for breast cancer.
| S-EPMC8581311 | biostudies-literature
Project description:Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced, or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.
| S-EPMC8196711 | biostudies-literature
Project description:Endocrine therapy (ET) of hormone receptor (HR)-positive and human epidermal growth factor receptor 2-(HER2)-negative metastatic breast cancer (MBC) historically focused on estrogen deprivation and antagonism. The identification of several intracellular pathways promoting resistance to antiestrogen therapy led to the introduction of novel endocrine drug combinations that reformed treatment schema and expanded therapeutic options. There is no doubt that efforts to overcome or delay resistance to ET are fruiting, particularly with the introduction of cyclin-dependent kinase 4/6 inhibitors such as palbociclib and ribociclib, and mechanistic target of rapamycin inhibitors such as everolimus. Although still considered incurable by currently available treatment modalities, many patients with MBC nowadays enjoy several years of good quality life coupled with decent tumor control. The diversity of therapies and unusual pattern of side effects can be quite perplexing to the treating physician. The sequence of variable agents and management of side effects, in addition to the timing of initiation of cytotoxic chemotherapy, is among the challenges faced by oncologists. In this review, we shed a spotlight on mechanisms of resistance to ET, and provide a review of landmark studies that have recently reshaped the landscape of treatment options for patients with metastatic HR-positive, HER2-negative MBC. A suggested treatment strategy for newly diagnosed patients is also discussed herein.
| S-EPMC5655644 | biostudies-literature
Project description:Developments in breast cancer treatment have resulted in reduction in breast cancer mortality in the developed world. However incidence continues to rise and greater use of preventive interventions including the use of therapeutic agents is needed to control this burden. High quality evidence from 9 major trials involving more than 83000 participants shows that selective oestrogen receptor modulators (SERMs) reduce breast cancer incidence by 38%. Combined results from 2 large trials with 8424 participants show that aromatase inhibitors (AIs) reduce breast cancer incidence by 53%. These benefits are restricted to prevention of ER positive breast cancers. Restricting preventive therapy to high-risk women improves the benefit-harm balance and many guidelines now encourage healthcare professionals to discuss preventive therapy in these women. Further research is needed to improve our risk-prediction models for the identification of high risk women for preventive therapy with greater accuracy and to develop surrogate biomarkers of response. Long-term follow-up of the IBIS-I trial has provided valuable insights into the durability of benefits from preventive therapy, and underscores the need for such follow up to fully evaluate other agents. Full utilisation of preventive therapy also requires greater knowledge and awareness among both doctors and patients about benefits, harms and risk factors. Healthcare professionals should routinely discuss preventive therapy with women at high-risk of breast cancer.
| S-EPMC6218009 | biostudies-literature
Project description:The most important modality of treatment in the two-thirds of patients with an estrogen receptor (ER)-positive early breast cancer is endocrine therapy. In postmenopausal women, options include the selective ER modulators (SERMs), tamoxifen and raloxifene, and the 'third-generation' aromatase inhibitors (AIs), anastrozole, exemestane and letrozole. Under the auspices of the National Institutes of Health Global Alliance for Pharmacogenomics, Japan, the Mayo Clinic Pharmacogenomics Research Network Center and the RIKEN Center for Genomic Medicine have worked collaboratively to perform genome-wide association studies (GWAS) in women treated with both SERMs and AIs. On the basis of the results of the GWAS, scientists at the Mayo Clinic have proceeded with functional genomic laboratory studies. As will be seen in this review, this has led to new knowledge relating to endocrine biology that has provided a clear focus for further research to move toward truly personalized medicine for women with breast cancer.
| S-EPMC3926210 | biostudies-literature
Project description:BackgroundEndocrine treatment is one of the most effective therapies for estrogen receptor-positive breast cancer. However, most tumors will develop resistance to endocrine therapy as the cancer progresses. This review focuses on the mechanisms and markers of endocrine-resistant breast cancer. In addition, current and future strategies to overcome endocrine resistance are discussed.SummarySeveral molecular mechanisms of endocrine resistance have been identified, including alterations in the ESR1 gene or in the PIK3CA/mTOR pathway. Meanwhile, CDK4/6, mTOR, and PI3K inhibition have shown to improve the efficacy of endocrine treatment and new promising approaches are being developed.Key messageOvercoming primary or acquired resistance to endocrine treatment remains a major challenge. Since the molecular mechanisms of endocrine resistance are manifold, optimal combination and sequencing strategies will have to be developed in the future.
| S-EPMC7490658 | biostudies-literature
Project description:BACKGROUND:In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. METHODS:Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. RESULTS:In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group. CONCLUSIONS:Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).
| S-EPMC6193457 | biostudies-literature
Project description:Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor ? (ER?) are among the most effective systemic treatments for ER?-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ER? transcriptional regulatory plasticity. Herein we identify VAV3 as a critical component in this process.A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ER? was evaluated by molecular docking analyses, an agonist fluoligand assay and short hairpin (sh)RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot analysis of signaling and proliferation markers, and shRNA-mediated protein depletion in viability and clonogenic assays, were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine its association with therapeutic response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression.The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase), but instead was likely a result of binding to ER?. VAV3 was selectively reduced upon exposure to YC-1 or ER? depletion, and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with the response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value?=?8.4?×?10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy.This study proposes VAV3 as a biomarker and a rationale for its use as a signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.
| S-EPMC4076632 | biostudies-literature
Project description:Adjuvant endocrine therapy reduces the risk of recurrence and death from breast cancer in women with hormone receptor-positive early breast cancer.Tamoxifen has been the standard therapy for decades, and this is still the case for pre-menopausal women.Ovarian suppression is of similar efficacy but currently there is no strong evidence for adding this to tamoxifen and the additional morbidity can be considerable. Results from two important trials addressing this issueare imminent. In post-menopausal women, aromatase inhibitors (AIs) (letrozole, anastrozole, or exemestane)are superior to tamoxifen in preventing recurrence but only letrozole has been shown to improve survival. The main gain is against high-risk cancers, and tamoxifen gives very similar benefit for low-risk disease. Traditionally, treatment has been given for around 5 years, but many women remain at risk of relapse for 10 years or more.The AIs, and more recently tamoxifen, have been shown to reduce further the risk of late recurrence in women still in remission after 5 years of tamoxifen if given for a further 5 years. The comparative benefits of these two options and the selection of patients most likely to benefit from long-term adjuvant endocrine therapy are important topics for further research, as is the optimum duration of AI therapy started upfront.
| S-EPMC4053079 | biostudies-literature
Project description:Breast cancer (BC) is the most common malignancy in women worldwide, with approximately two-thirds having hormone receptor-positive (HR+) tumors. New endocrine therapy (ET) strategies include combining ET agents as well as adding inhibitors targeting growth factors, angiogenesis, the mechanistic target of rapamycin, phosphoinositide 3-kinase (PI3K), or cyclin-dependent kinase 4/6 to ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib plus letrozole as first-line therapy for HR+/HER- advanced BC with special consideration for the former in ET-naïve patients, as well as everolimus plus exemestane or palbociclib plus fulvestrant as second-line therapy with special consideration in select first-line patients. Although the safety profiles of these combinations are generally predictable and manageable, both everolimus and palbociclib are associated with an increased risk of potentially serious or early-onset toxicities requiring individualized a priori adverse event risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Although each of these combinations improves progression-free survival, none with the exception of anastrazole plus fulvestrant have demonstrated improved overall survival. PI3K catalytic-? mutations assessed from circulating tumor DNA represent the first potentially viable serum biomarker for the selection of ET combinations, and new data demonstrate the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis. Therapeutic ratios of select ET combinations support their use in first- and second-line settings, but optimal sequencing has yet to be determined.2017;22:12-24 IMPLICATIONS FOR PRACTICE: Emerging data show that new endocrine therapy (ET) combinations can improve progression-free and overall survival outcomes in patients with hormone receptor-positive, HER2-negative (HR+/HER-) advanced breast cancer. Level 1 evidence supports consideration of dual ET regimens, particularly in ET-naïve patients, or palbociclib plus letrozole as first-line therapy, as well as the addition of mTOR or CDK4/6 inhibitors to established ET in the second-line setting and in select first-line patients. Some combinations are associated with increased risk of class-specific toxicities that will require individualized risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Recent data on a noninvasive biomarker assay that predicts response to a phosphoinositide 3-kinase inhibitor demonstrates the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis.
| S-EPMC5313264 | biostudies-other