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The Cochrane Database of Systematic... Jan 2022Adjuvant aromatase inhibitors (AI) improve survival compared to tamoxifen in postmenopausal women with hormone receptor-positive stage I to III breast cancer. In... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adjuvant aromatase inhibitors (AI) improve survival compared to tamoxifen in postmenopausal women with hormone receptor-positive stage I to III breast cancer. In approximately half of these women, AI are associated with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS), often described as symmetrical pain and soreness in the joints, musculoskeletal pain and joint stiffness. AIMSS may have significant and prolonged impact on women's quality of life. AIMSS reduces adherence to AI therapy in up to a half of women, potentially compromising breast cancer outcomes. Differing systemic therapies have been investigated for the prevention and treatment of AIMSS, but the effectiveness of these therapies remains unclear.
OBJECTIVES
To assess the effects of systemic therapies on the prevention or management of AIMSS in women with stage I to III hormone receptor-positive breast cancer.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, WHO International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov registries to September 2020 and the Cochrane Breast Cancer Group (CBCG) Specialised Register to March 2021. SELECTION CRITERIA: We included all randomised controlled trials that compared systemic therapies to a comparator arm. Systemic therapy interventions included all pharmacological therapies, dietary supplements, and complementary and alternative medicines (CAM). All comparator arms were allowed including placebo or standard of care (or both) with analgesia alone. Published and non-peer-reviewed studies were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies, extracted data, and assessed risk of bias and certainty of the evidence using the GRADE approach. Outcomes assessed were pain, stiffness, grip strength, safety data, discontinuation of AI, health-related quality of life (HRQoL), breast cancer-specific quality of life (BCS-QoL), incidence of AIMSS, breast cancer-specific survival (BCSS) and overall survival (OS). For continuous outcomes, we used vote-counting by reporting how many studies reported a clinically significant benefit within the confidence intervals (CI) of the mean difference (MD) between treatment arms, as determined by the minimal clinically importance difference (MCID) for that outcome scale. For dichotomous outcomes, we reported outcomes as a risk ratio (RR) with 95% CI.
MAIN RESULTS
We included 17 studies with 2034 randomised participants. Four studies assessed systemic therapies for the prevention of AIMSS and 13 studies investigated treatment of AIMSS. Due to the variation in systemic therapy studies, including pharmacological, and CAM, or unavailable data, meta-analysis was limited, and only two trials were combined for meta-analysis. The certainty of evidence for all outcomes was either low or very low certainty. Prevention studies The evidence is very uncertain about the effect of systemic therapies on pain (from baseline to the end of the intervention; 2 studies, 183 women). The two studies, investigating vitamin D and omega-3 fatty acids, showed a treatment effect with 95% CIs that did not include an MCID for pain. Systemic therapies may have little to no effect on grip strength (RR 1.08, 95% CI 0.37 to 3.17; 1 study, 137 women) or on women continuing to take their AI (RR 0.16, 95% 0.01 to 2.99; 1 study, 147 women). The evidence suggests little to no effect on HRQoL and BCS-QoL from baseline to the end of intervention (the same single study; 44 women, both quality of life outcomes showed a treatment effect with 95% CIs that did include an MCID). The evidence is very uncertain for outcomes assessing incidence of AIMSS (RR 0.82, 95% CI 0.63 to 1.06; 2 studies, 240 women) and the safety of systemic therapies (4 studies, 344 women; very low-certainty evidence). One study had a US Food and Drug Administration alert issued for the intervention (cyclo-oxygenase-2 inhibitor) during the study, but there were no serious adverse events in this or any study. There were no data on stiffness, BCSS or OS. Treatment studies The evidence is very uncertain about the effect of systemic therapies on pain from baseline to the end of intervention in the treatment of AIMSS (10 studies, 1099 women). Four studies showed an MCID in pain scores which fell within the 95% CI of the measured effect (vitamin D, bionic tiger bone, Yi Shen Jian Gu granules, calcitonin). Six studies showed a treatment effect with 95% CI that did not include an MCID (vitamin D, testosterone, omega-3 fatty acids, duloxetine, emu oil, cat's claw). The evidence was very uncertain for the outcomes of change in stiffness (4 studies, 295 women), HRQoL (3 studies, 208 women) and BCS-QoL (2 studies, 147 women) from baseline to the end of intervention. The evidence suggests systemic therapies may have little to no effect on grip strength (1 study, 107 women). The evidence is very uncertain about the safety of systemic therapies (10 studies, 1250 women). There were no grade four/five adverse events reported in any of the studies. The study of duloxetine reported more all-grade adverse events in this treatment group than comparator group. There were no data on the incidence of AIMSS, the number of women continuing to take AI, BCCS or OS from the treatment studies.
AUTHORS' CONCLUSIONS
AIMSS are chronic and complex symptoms with a significant impact on women with early breast cancer taking AI. To date, evidence for safe and effective systemic therapies for prevention or treatment of AIMSS has been minimal. Although this review identified 17 studies with 2034 randomised participants, the review was challenging due to the heterogeneous systemic therapy interventions and study methodologies, and the unavailability of certain trial data. Meta-analysis was thus limited and findings of the review were inconclusive. Further research is recommended into systemic therapy for AIMSS, including high-quality adequately powered RCT, comprehensive descriptions of the intervention/placebo, and robust definitions of the condition and the outcomes being studied.
Topics: Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Musculoskeletal Pain; Quality of Life; Tamoxifen
PubMed: 35005781
DOI: 10.1002/14651858.CD013167.pub2 -
Journal of Alternative and... May 2015Acupuncture has been used as a complementary medical treatment for arthralgia and other types of pain. The objective of this review is to assess the effectiveness of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Acupuncture has been used as a complementary medical treatment for arthralgia and other types of pain. The objective of this review is to assess the effectiveness of acupuncture in the treatment of arthralgia in patients with breast cancer who were treated with aromatase inhibitors (AIs).
METHODS
A literature search was performed, without language restrictions, of 10 databases from their inception through February 2014. The literature reviewed included randomized clinical trials (RCTs) and clinical trials that compared real versus sham acupuncture for the treatment of AI-related musculoskeletal symptoms (AIMSS). The methodologic quality of these trials was assessed by using the modified Jadad Quality Scale. Meta-analytic software (RevMan 5.0) was used to analyze the data.
RESULTS
Five To compare the effects of real versus sham acupuncture, five RCTs were assessed by meta-analysis and quality analysis. Three of the RCTs reported favorable effects with regard to use of acupuncture in reducing pain and joint-related symptoms, while the other two RCTs did not. The meta-analysis showed trends toward reduced pain and stiffness in patients given acupuncture compared with those who received sham treatment (n=82; pain, mean difference: -2.07 [95% confidence interval (CI), -4.72 to 0.57]; p=0.12; stiffness, mean difference: -86.10 [95% CI, -249.11 to 76.92]; p=0.30), although these differences were not statistically significant.
CONCLUSIONS
Acupuncture has been reported as a safe and promising treatment for AIMSS, but the present analysis indicated that the effects were not statistically significant. Other outcome measurements, such as imaging studies, would be worth including in future studies to further confirm the efficacy of acupuncture in AIMSS.
Topics: Acupuncture Therapy; Aromatase Inhibitors; Arthralgia; Breast Neoplasms; Female; Humans
PubMed: 25915433
DOI: 10.1089/acm.2014.0083 -
Current Oncology (Toronto, Ont.) Mar 2015Cancer Care Ontario's Program in Evidence-Based Care (pebc) recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The... (Review)
Review
BACKGROUND
Cancer Care Ontario's Program in Evidence-Based Care (pebc) recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question "What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?" The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and her2 (human epidermal growth factor receptor 2)-targeted therapy.
METHODS
For the systematic review, the literature in the medline and embase databases was searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses.
RESULTS
Several hundred documents that met the inclusion criteria were retrieved. Meta-analyses from the Early Breast Cancer Trialists' Collaborative Group encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews.
SUMMARY
The results of the systematic review constitute a comprehensive compilation of high-level evidence, which was the basis for the 2014 pebc guideline on systemic therapy for early breast cancer. The review of the evidence for systemic endocrine therapy (adjuvant tamoxifen, aromatase inhibitors, and ovarian ablation and suppression) is presented here; the evidence for chemotherapy and her2-targeted treatment-and the final clinical practice recommendations-are presented separately in this supplement.
PubMed: 25848344
DOI: 10.3747/co.22.2326 -
Cancer Medicine Jan 2019Breast cancer (BC) is the most common cancer among women worldwide. With increasing survival rates, focus has expanded to long-term adverse effects of adjuvant...
INTRODUCTION
Breast cancer (BC) is the most common cancer among women worldwide. With increasing survival rates, focus has expanded to long-term adverse effects of adjuvant chemotherapy and/or aromatase inhibitors. Weight gain during chemotherapy has been well documented, but the underlying mechanisms remain unclear. A change in glucose and insulin metabolism is a possible consequence.
METHODS
We searched PubMed on the 4th of May 2018, and found eight articles that compared measurements of glucose and insulin before and after chemotherapy and/or aromatase inhibitors in woman with BC.
RESULTS
A general trend of increased glucose and insulin is seen and likely to be caused by weight gain and/or changes in body composition as a consequence of adjuvant treatment of BC.
DISCUSSION
Due to methodological limitations including short follow-up times and small sample sizes, further studies are required to better describe metabolic consequences of adjuvant chemotherapy and/or aromatase inhibitors. Future studies could help identify patients in high-risk of developing cardiometabolic disease after BC treatment.
Topics: Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Glucose; Humans; Insulin
PubMed: 30561133
DOI: 10.1002/cam4.1911 -
Breast (Edinburgh, Scotland) Aug 2021Hormone Therapy (HT) reduces the risk of breast cancer recurrence and mortality in women with breast cancer. Despite these clinical benefits, rates of HT non-adherence... (Review)
Review
BACKGROUND
Hormone Therapy (HT) reduces the risk of breast cancer recurrence and mortality in women with breast cancer. Despite these clinical benefits, rates of HT non-adherence and non-persistence are high. Research suggests this may be due to the impact of HT side effects. However, little research has explored the individual contribution of side effects to non-adherence and non-persistence behaviours, thereby hindering the implementation of targeted intervention strategies. Our aim is to review the published literature on breast cancer survivors' lived experiences of HT side effects and explore how these may be related to non-adherence and non-persistence behaviour.
METHODS
Electronic searches were conducted from inception to May 2020, utilising Cochrane CENTRAL, Medline, Embase, Web of Science and PsycINFO databases. Searches included a combination of terms related to breast cancer, adherence, hormone therapy and side effects.
RESULTS
Sixteen eligible papers were identified, and study quality was high. Data were thematically synthesised into four analytical themes, which encompassed 13 descriptive sub-themes: 'Daily impact of side-effects', 'Role of Health Care Professionals', 'Managing HT side-effects', and 'Weighing up the pros and cons'.
CONCLUSIONS
HT side effects significantly impact breast cancer survivor's quality of life. A lack of support from healthcare providers leads to self-management strategies, which negatively affects adherence and persistence behaviour.
Topics: Breast Neoplasms; Cancer Survivors; Female; Hormones; Humans; Medication Adherence; Neoplasm Recurrence, Local; Quality of Life
PubMed: 34049260
DOI: 10.1016/j.breast.2021.05.005 -
Cancer Medicine Jan 2023Breast cancer (BC) is a common type of cancer in women. Advances in therapy options have resulted in higher overall survival rates but side effects of cancer treatment... (Review)
Review
INTRODUCTION
Breast cancer (BC) is a common type of cancer in women. Advances in therapy options have resulted in higher overall survival rates but side effects of cancer treatment are increasingly in the spotlight. The beneficial effects of anti-oestrogen therapy with tamoxifen and letrozole in the prevention of BC recurrence are well documented. While the most common side-effects of this therapy are well-defined, less is known about its effects on thyroid function. In women treated for early BC, an average of 1-5 kg weight gain has been observed after treatment with chemotherapy/anti-oestrogens. We aim to evaluate the current knowledge on the side effects of tamoxifen and letrozole treatments on thyroid function, followed by its potential influence on the observed weight gain.
METHODS
We searched PubMed and found 16 publications on thyroid function and tamoxifen treatment in pre- and post-menopausal women with early- and advanced BC, whereas five publications on letrozole treatment in post-menopausal women with advanced BC.
RESULTS
According to the current literature, there is an overall tendency towards a mild and transient thyroid dysfunction, that is, subclinical hypothyroidism in tamoxifen-treated patients. Only one publication reported further significant changes in thyroid hormones beyond one year of tamoxifen treatment. No significant changes in thyroid function have been observed among letrozole-treated patients.
CONCLUSION
Tamoxifen-treated patients can develop mild and transient thyroid dysfunction within the first 12 months, yet further significant changes in thyroid function beyond one year of tamoxifen treatment have been reported in a single study. There is no evidence of thyroid dysfunction in letrozole-treated patients. Current literature does not focus on subclinical hypothyroidism as a possible cause of weight gain in patients with BC. Subgrouping of BC patients and studies with a longer observation of thyroid hormones and weight changes during and after anti-oestrogen treatment are needed to further elucidate how anti-oestrogens affect thyroid function.
Topics: Humans; Female; Letrozole; Breast Neoplasms; Tamoxifen; Aromatase Inhibitors; Nitriles; Triazoles; Neoplasm Recurrence, Local; Estrogens; Hypothyroidism; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant
PubMed: 35748065
DOI: 10.1002/cam4.4949 -
Journal of Clinical Medicine Mar 2024Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid... (Review)
Review
Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia.
PubMed: 38542042
DOI: 10.3390/jcm13061818 -
Taiwanese Journal of Obstetrics &... Aug 2016Endometrial stromal tumors are rare uterine tumors (<1%). Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS),... (Review)
Review
Endometrial stromal tumors are rare uterine tumors (<1%). Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and uterine undifferentiated sarcoma (UUS). This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B) gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS). Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors.
Topics: Aged; Endometrial Neoplasms; Female; Humans; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Risk Factors; Sarcoma, Endometrial Stromal
PubMed: 27590366
DOI: 10.1016/j.tjog.2016.04.034 -
Clinical Breast Cancer Apr 2022Concerns around pharmacological interaction between tamoxifen and antidepressants have resulted in evidence-base guidelines that recommend avoidance or caution with... (Review)
Review
Concerns around pharmacological interaction between tamoxifen and antidepressants have resulted in evidence-base guidelines that recommend avoidance or caution with concurrent use. It remains unclear however whether this interaction is clinically important. A systematic review of studies comparing endocrine therapy (including tamoxifen and aromatase inhibitors) alone or concurrent with antidepressants in breast cancer patients was performed. The literature search sought studies within MEDLINE, EMBASE, and the Cochrane Collaboration Library published from database inception until December 1, 2020. Outcomes of interest included recurrence, breast cancer-specific survival, overall mortality, quality of life, and treatment compliance. Studies were assessed with the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle Ottawa tool for case-control and cohort studies. From 695 citations, we included 15 studies (2 randomized controlled trials [255 patients], 10 retrospective cohort studies [75,678 patients], and 3 case-control studies [18,836 patients]). While between-study clinical and methodologic differences (including analysis of confounding variables) precluded formal meta-analysis, findings from included studies did not find consistent evidence that concurrent use of antidepressants (including paroxetine) with tamoxifen therapy has negative impacts on the outcomes of interest. In this systematic review, despite data from nearly 100,000 patients, concurrent use of tamoxifen and antidepressants showed no consistent negative effect on clinical outcomes. Given the recognized harm to patients of changing either endocrine therapy or antidepressants to avoid concurrent use, current evidence-based guidelines should be updated accordingly. More rigorously designed pharmacoepidemiologic studies are needed.
Topics: Antidepressive Agents; Breast Neoplasms; Female; Humans; Practice Guidelines as Topic; Quality of Life; Retrospective Studies; Tamoxifen
PubMed: 34740542
DOI: 10.1016/j.clbc.2021.10.003 -
Acta Obstetricia Et Gynecologica... Sep 2015Our objective was to compare the effectiveness of metformin plus clomiphene citrate vs. gonadotrophins, laparoscopic ovarian diathermy, aromatase inhibitors,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Our objective was to compare the effectiveness of metformin plus clomiphene citrate vs. gonadotrophins, laparoscopic ovarian diathermy, aromatase inhibitors, N-acetyl-cysteine and other insulin sensitizers+clomiphene for improving fertility outcomes in women with clomiphene-resistant polycystic ovary syndrome.
DESIGN
PubMed, SCOPUS and CENTRAL databases were searched until April 2014 with the key words: PCOS, polycystic ovary syndrome, metformin, clomiphene citrate, ovulation induction and pregnancy. The search was limited to articles conducted with humans and published in English.
SAMPLE
The PRISMA statement was followed. Twelve randomized controlled trials (n = 1411 women) were included.
MAIN OUTCOME MEASURES
Ovulation and clinical pregnancy rates per woman randomized.
RESULTS
Compared with gonadotrophins, the metformin+clomiphene combination resulted in significantly fewer ovulations (odds ratio 0.25; 95% confidence interval 0.15-0.41; p < 0.00001, 3 trials, I(2) = 85%, n = 323) and pregnancies (odds ratio 0.45; 95% confidence interval 0.27-0.75; p = 0.002, 3 trials, I(2) = 0%, n = 323). No significant differences were found when metformin+clomiphene was compared with laparoscopic ovarian diathermy (odds ratio 0.88; 95% confidence interval 0.53-1.47; p = 0.62, 1 trial, n = 282; odds ratio 0.96; 95% confidence interval 0.60-1.54; p = 0.88, 2 trials, I(2) = 0%, n = 332, for ovulation and pregnancy rates, respectively). Likewise, no differences were observed in comparison with aromatase inhibitors (odds ratio 0.88; 95% confidence interval 0.58-1.34; p = 0.55, 3 trials, I(2) = 3%, n = 409; odds ratio 0.85; 95% confidence interval 0.53-1.36; p = 0.50, 2 trials, n = 309, for ovulation and pregnancy rates, respectively).
CONCLUSIONS
There is evidence for the superiority of gonadotrophins, but the metformin+clomiphene combination is mainly relevant for clomiphene-resistant polycystic ovary syndrome patients and, if not effective, a next step could be gonadotrophins. More attempts with metformin+clomiphene are only relevant if there is limited access to gonadotrophins.
Topics: Clomiphene; Drug Therapy, Combination; Female; Fertility Agents, Female; Humans; Hypoglycemic Agents; Metformin; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate
PubMed: 25965123
DOI: 10.1111/aogs.12673