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  1. Madden SF, Cremona M, Farrelly AM, Low WH, McBryan J
    Cancer Gene Ther, 2023 Feb;30(2):324-334.
    PMID: 36266450 DOI: 10.1038/s41417-022-00548-0
    To prevent the development of endocrine-resistant breast cancer, additional targeted therapies are increasingly being trialled in combination with endocrine therapy. The molecular mechanisms facilitating cancer cell survival during endocrine treatment remain unknown but could help direct selection of additional targeted therapies. We present a novel proteomic timecourse dataset, profiling potential drug targets in a population of MCF7 cells during 1 year of tamoxifen treatment. Reverse phase protein arrays profiled >70 proteins across 30 timepoints. A biphasic response to tamoxifen was evident, which coincided with changes in growth rate. Tamoxifen strongly impeded cell growth for the first 160 days, followed by gradual growth recovery and eventual resistance development. The growth-impeded phase was distinguished by the phosphorylation of Stat3 (y705) and Src (y527). Tumour tissue from patients treated with neo-adjuvant endocrine therapy (<4 months) also displayed increased Stat3 and Src signalling. Inhibitors of Stat3 (napabucasin) and Src (dasatinib), were effective at killing tamoxifen-treated MCF7 and T47D cells. Sensitivity to both drugs was significantly enhanced once tamoxifen had induced the growth-impeded phase. This novel proteomic resource identifies key mechanisms enabling cell survival during tamoxifen treatment. It provides valuable insight into potential drug combinations and timing that may prevent the development of endocrine resistance.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  2. Love RR, Hossain SM, Hussain MM, Mostafa MG, Laudico AV, Siguan SS, et al.
    Eur J Cancer, 2016 06;60:107-16.
    PMID: 27107325 DOI: 10.1016/j.ejca.2016.03.011
    PURPOSE: In premenopausal women with metastatic hormone receptor-positive breast cancer, hormonal therapy is the first-line therapy. Gonadotropin-releasing hormone analogue + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favourably influenced long-term outcomes.

    METHODS: Two hundred forty-nine premenopausal women with incurable or metastatic hormone receptor-positive breast cancer entered a trial in which they were randomised to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression-free survival (PFS) in the two randomised groups and by hormone-confirmed menstrual cycle phase.

    RESULTS: Overall survival (OS) and PFS were not demonstrated to be different in the two randomised groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels <2 ng/ml (anovulatory patients; adjusted hazard ratio 1.46, 95% confidence interval [CI]: 0.89-2.41, p = 0.14) compared with those in luteal phase with progesterone level of 2 ng/ml or higher. Median OS was 2 years (95% CI: 1.7-2.3) and OS at 4 years was 26%.

    CONCLUSIONS: The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT00293540.

    Study site: Bangladesh, The Philippines, China, Nigeria,
    Indonesia, Malaysia, Taiwan, Morocco, and Vietnam
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use*
  3. Othman NH, Othman MS, Ismail AN, Mohammad NZ, Ismail Z
    Aust N Z J Obstet Gynaecol, 1996 May;36(2):216-8.
    PMID: 8798320
    A 30-year old female who initially had typical endometriosis treated according to a standard regimen later developed numerous highly vascular endometrial polyps on the vagina, cervix, ureter, serosal surfaces of the uterus, pouch of Douglas (POD) and other areas of pelvic peritoneum as well as the endometrium 8 months after withdrawal of treatment with Zoladex gonadotrophin releasing hormone (GnRH) agonist used for treatment of this disease. We postulate that these polyps developed as a rebound phenomenon upon withdrawal of Zoladex. We believe this is the first report of this complication following use of GnRH analogue.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  4. Bhoo-Pathy N, Balakrishnan N, See MH, Taib NA, Yip CH
    World J Surg, 2016 12;40(12):2913-2921.
    PMID: 27456497 DOI: 10.1007/s00268-016-3658-z
    BACKGROUND: Factors associated with surgery, adjuvant radiotherapy, and chemotherapy and whether there were missed opportunities for treatment in elderly patients were determined in an Asian setting.

    METHODS: All 5616 patients, diagnosed with breast cancer in University Malaya Medical Centre from 1999 to 2013 were included. In 945 elderly patients (aged 65 years and above), multivariable logistic regression was performed to identify factors associated with treatment, following adjustment for age, ethnicity, tumor, and other treatment characteristics. The impact of lack of treatment on survival of the elderly was assessed while accounting for comorbidities.

    RESULTS: One in five elderly patients had comorbidities. Compared to younger patients, the elderly had more favorable tumor characteristics, and received less loco-regional treatment and chemotherapy. Within stage I-IIIa elderly breast cancer patients, 10 % did not receive any surgery. These patients were older, more likely to be Malays, have comorbidities, and bigger tumors. In elderlies with indications for adjuvant radiotherapy, no irradiation (30 %) was associated with increasing age, comorbidity, and the absence of systemic therapy. Hormone therapy was optimal, but only 35 % of elderly women with ER negative tumors received chemotherapy. Compared to elderly women who received adequate treatment, those not receiving surgery (adjusted hazard ratio: 2.30, 95 %CI: 1.10-4.79), or radiotherapy (adjusted hazard ratio: 1.56, 95 %CI: 1.10-2.19), were associated with higher mortality. Less than 25 % of the survival discrepancy between elderly women receiving loco-regional treatment and no treatment were attributed to excess comorbidities in untreated patients.

    CONCLUSION: While the presence of comorbidities significantly influenced loco-regional treatment decisions in the elderly, it was only able to explain the lower survival rates in untreated patients up to a certain extent, suggesting missed opportunities for treatment.

    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use*
  5. Bhoo-Pathy N, Verkooijen HM, Taib NA, Hartman M, Yip CH
    Br J Surg, 2011 Nov;98(11):1566-72.
    PMID: 21858791 DOI: 10.1002/bjs.7650
    Advanced breast cancer is common in less affluent parts of Asia. The impact of breast surgery on survival of women presenting with metastatic breast cancer in this setting was investigated.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  6. Ngoo KS, Rohaizak M, Naqiyah I, Shahrun Niza AS
    Singapore Med J, 2009 May;50(5):519-21.
    PMID: 19495524
    Breast cancer is a rare condition among men with a reported incidence of about one percent. Nevertheless, it is thought to behave similarly in both genders. Due to its rarity, male breast cancer is not widely reported, especially in the Asian population.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  7. Teh LK, Mohamed NI, Salleh MZ, Rohaizak M, Shahrun NS, Saladina JJ, et al.
    AAPS J, 2012 Mar;14(1):52-9.
    PMID: 22183189 DOI: 10.1208/s12248-011-9313-6
    CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  8. Chin FW, Chan SC, Abdul Rahman S, Noor Akmal S, Rosli R
    Breast J, 2016 Jan-Feb;22(1):54-62.
    PMID: 26510986 DOI: 10.1111/tbj.12518
    The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. In Malaysia, the knowledge on CYP2D6 genetic polymorphisms as well as metabolizer status in Malaysian breast cancer patients remains unknown. Hence, this study aimed to comprehensively identify CYP2D6 genetic polymorphisms among 80 Malaysian breast cancer patients. The genetic polymorphisms of all the 9 exons of CYP2D6 gene were identified using high-resolution melting analysis and confirmed by DNA sequencing. Seven CYP2D6 alleles consisting of CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*10, CYP2D6*39, CYP2D6*49, and CYP2D6*75 were identified in this study. Among these alleles, CYP2D6*10 is the most common allele in both Malaysian Malay (54.8%) and Chinese (71.4%) breast cancer patients, whereas CYP2D6*4 in Malaysian Indian (28.6%) breast cancer patients. In relation to CYP2D6 genotype, CYP2D6*10/*10 is more frequently observed in both Malaysian Malay (28.9%) and Chinese (57.1%) breast cancer patients, whereas CYP2D6*4/*10 is more frequently observed in Malaysian Indian (42.8%) breast cancer patients. In terms of CYP2D6 phenotype, 61.5% of Malaysian Malay breast cancer patients are predicted as extensive metabolizers in which they are most likely to respond well to tamoxifen therapy. However, 57.1% of Chinese as well as Indian breast cancer patients are predicted as intermediate metabolizers and they are less likely to gain optimal benefit from the tamoxifen therapy. This is the first report of CYP2D6 genetic polymorphisms and phenotypes in Malaysian breast cancer patients for different ethnicities. These data may aid clinicians in selecting an optimal drug therapy for Malaysian breast cancer patients, hence improve the clinical outcome of the patients.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  9. Razak MA, Fazir M
    Med J Malaysia, 2000 Sep;55 Suppl C:97-100.
    PMID: 11200052
    A rare case of an aggressive recurrent giant cell tumour of axis is presented. The problems encountered in diagnosis and management are discussed. High dose dexamethasone was found to be useful managing this inoperable aggressive tumour which was compressing the cord. Early diagnosis would facilitate wide excision of the tumour with good prognosis.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  10. Gao Y, Zhang W, Liu C, Li G
    Sci Rep, 2019 12 11;9(1):18844.
    PMID: 31827114 DOI: 10.1038/s41598-019-54289-6
    Resistance to tamoxifen is a major clinical challenge. Research in recent years has identified epigenetic changes as mediated by dysregulated miRNAs that can possibly play a role in resistance to tamoxifen in breast cancer patients expressing estrogen receptor (ER). We report here elevated levels of EMT markers (vimentin and ZEB1/2) and reduced levels of EMT-regulating miR-200 (miR-200b and miR-200c) in ER-positive breast cancer cells, MCF-7, that were resistant to tamoxifen, in contrast with the naïve parental MCF-7 cells that were sensitive to tamoxifen. Further, we established regulation of c-MYB by miR-200 in our experimental model. C-MYB was up-regulated in tamoxifen resistant cells and its silencing significantly decreased resistance to tamoxifen and the EMT markers. Forced over-expression of miR-200b/c reduced c-MYB whereas reduced expression of miR-200b/c resulted in increased c-MYB We further confirmed the results in other ER-positive breast cancer cells T47D cells where forced over-expression of c-MYB resulted in induction of EMT and significantly increased resistance to tamoxifen. Thus, we identify a novel mechanism of tamoxifen resistance in breast tumor microenvironment that involves miR-200-MYB signaling.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  11. Mohamad NV, Soelaiman IN, Chin KY
    Endocr Metab Immune Disord Drug Targets, 2017 Nov 16;17(4):276-284.
    PMID: 28925899 DOI: 10.2174/1871530317666170919112757
    BACKGROUND AND OBJECTIVE: Prostate cancer is the most prevalent non-cutaneous cancer in men, which causes significant mortality among the patients. Since prostate cancer cells are stimulated by androgen, effective androgen ablation in men is one of the essential strategies in the management of prostate cancer.

    DISCUSSION: Several treatment options are available for different stages of prostate cancer. Hormone therapy known as androgen deprivation therapy (ADT) is the first line treatment used to treat advanced prostate cancer. Chemical castration by gonadotropin-releasing hormone agonists suppresses lutenizing hormone production, which in turn inhibits the production of testosterone and dihydrotestosterone. This will prevent the growth of prostate cancer cells. However, ADT causes deleterious effects on bone health because the androgens are essential in preserving optimal bone health in men.

    CONCLUSION: Various observational studies showed that long-term ADT for advanced or metastatic prostate cancer was associated with decreased bone mineral density, as well as altered body composition that might affect bone health. Considering the potential impact of osteoporotic fracture, interventions to mitigate these skeletal adverse effects should be considered by physicians when initiating ADT on their patients.

    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use*
  12. Raihan J, Ahmad U, Yong YK, Eshak Z, Othman F, Ideris A
    BMC Cancer, 2019 Apr 04;19(1):315.
    PMID: 30947706 DOI: 10.1186/s12885-019-5516-5
    BACKGROUND: Different strains of Newcastle disease virus (NDV) worldwide proved to have tumouricidal activity in several types of cancer cells. However, the possible anti-cancer activity of Malaysian NDV AF2240 strain and its mechanism of action remains unknown. The ability of cytokine-related apoptosis-inducing NDV AF2240 to treat breast cancer was investigated in the current study.

    METHODS: A total of 90 mice were used and divided into 15 groups, each group comprising of 6 mice. Tumour, body weight and mortality of the mice were determined throughout the experiment, to observe the effect of NDV and NDV + tamoxifen treatments on the mice. In addition, the toxic effect of the treatments was determined through liver function test. In order to elucidate the involvement of cytokine production induced by NDV, a total of six cytokines, i.e. IL-6, IFN-γ, MCP-1, IL-10, IL12p70 and TNF-α were measured using cytometric bead array assay (plasma) and enzyme-linked immunosorbent spot (isolated splenocytes).

    RESULTS: The results demonstrated that 4 T1 breast cancer cells in allotransplanted mice treated with AF2240 showed a noticeable inhibition of tumour growth and induce apoptotic-related cytokines.

    CONCLUSIONS: NDV AF2240 suppression of breast tumour growth is associated with induction of apoptotic-related cytokines. It would be important to further investigate the molecular mechanism underlaying cytokines production by Newcastle disease virus.

    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  13. Chong HY, Taib NA, Rampal S, Saad M, Bustam AZ, Yip CH
    Asian Pac J Cancer Prev, 2010;11(4):913-7.
    PMID: 21133600
    BACKGROUND: Locally advanced breast cancer (LABC) is characterized by the presence of a large primary tumour (>5 cm) associated with or without skin or chest-wall involvement (T4) or with fixed (matted) axillary lymph nodes in the absence of any evidence of distant metastases. These cancers are classified as stage IIIA and IIIB according to the AJCC Staging System. Treatment of choice involves combinations of surgery, chemotherapy, radiotherapy and/or hormonal therapy. Current guidelines recommend primary surgery or neoadjuvant therapy followed by surgery. The primary objective of this study was to compare the outcome of LABC patients subjected to neoadjuvant chemotherapy before surgery and those who underwent surgery as the primary treatment and to determine prognostic predictors. Secondary objectives were to evaluate the response after neoadjuvant therapy and to determine the treatment compliance rate.

    METHODS: This retrospective study of Stage III breast cancer patients was conducted over a 5 year period from 1998 to 2002. The survival data were obtained from the National Registry of Births and Deaths with the end-point of the study in April 2006. The Kaplan Meier method was applied for survival analysis. Cox regression analysis by stepwise selection was performed to identify important prognostic factors.

    RESULTS: Out of a 155 evaluable patients, 74 (47.7%) had primary surgery, 62 (40%) had neoadjuvant chemotherapy, 10 patients (6.5%) were given Tamoxifen as the primary treatment, while 9 patients (5.8%) defaulted any form of treatment. After neoadjuvant chemotherapy, 9 patients defaulted further treatment, leaving 53 evaluable patients. Out of these 53 evaluable patients, 5 patients (9.4%) had complete pathological response, 5 (9.4%) a complete clinical response, and 26 (49.1%) had partial response after neoadjuvant chemotherapy. The 5-year survival in the primary surgery group was 56.7 % compared to 44.7% in the neoadjuvant chemotherapy group (p<0.01). The important prognostic factors were race, size of tumour, nodal status, estrogen receptor status and response to neoadjuvant chemotherapy.

    CONCLUSION: Patients who had primary surgery had better survival than those who underwent neoadjuvant chemotherapy, which may be due to bias in the selection of patients for neoadjuvant chemotherapy. Out of a total of 155 patients, 25.1% defaulted part of the treatment, or did not receive optimal treatment, emphasizing the importance of psychosocial support and counselling for this group of patients.

    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  14. Mydin AR, Dunne MT, Finn MA, Armstrong JG
    Int J Radiat Oncol Biol Phys, 2013 Jan 1;85(1):101-8.
    PMID: 22658512 DOI: 10.1016/j.ijrobp.2012.03.001
    PURPOSE: To assess the survival benefit of early vs late salvage hormonal therapy (HT), we performed a secondary analysis on patients who developed recurrence from Irish Clinical Oncology Research Group 97-01, a randomized trial comparing 4 vs 8 months neoadjuvant HT plus radiation therapy (RT) in intermediate- and high-risk prostate adenocarcinoma.
    METHODS AND MATERIALS: A total of 102 patients from the trial who recurred were analyzed at a median follow-up of 8.5 years. The patients were divided into 3 groups based on the timing of salvage HT: 57 patients had prostate-specific antigen (PSA)≤10 ng/mL and absent distant metastases (group 1, early), 21 patients had PSA>10 ng/mL and absent distant metastases (group 2, late), and 24 patients had distant metastases (group 3, late). The endpoint analyzed was overall survival (OS) calculated from 2 different time points: date of enrolment in the trial (OS1) and date of initiation of salvage HT (OS2). Survival was estimated using Kaplan-Meier curves and a Cox regression model.
    RESULTS: The OS1 differed significantly between groups (P
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use*
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