Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms and fatigue in women with breast cancer starting adjuvant letrozole: The VITAL trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9000-9000 ◽  
Author(s):  
Qamar J. Khan ◽  
Bruce F. Kimler ◽  
Pavan S. Reddy ◽  
Priyanka Sharma ◽  
Jennifer R. Klemp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Trial ◽  
Aromatase Inhibitors ◽  
Vitamin D3 ◽  
Joint Pain ◽  
Positive Impact ◽  
Standard Dose ◽  
Musculoskeletal Symptoms ◽  
Pain Disability ◽  
The Impact

9000 Background: Musculoskeletal (MS) pain and fatigue are common in women on adjuvant Aromatase Inhibitors (AIs) and lead to reduced compliance. Pilot studies suggest a positive impact of vit D on MS pain and disability from AIs. We conducted a bi-institutional, double blind, placebo controlled randomized trial to study the impact of 30,000 I.U of vit D3 in preventing worsening of MS pain and fatigue in women starting letrozole. Methods: Women with stage I-III breast cancer starting adjuvant AI and a 25(OH)D level of 40 ng/ml or less were eligible. Women with prior renal stones or hypercalcemia were excluded. All subjects received letrozole, plus standard dose vitD3 (600 IU) and calcium (1200 mg) daily, all provided by the study. Women were randomly assigned to 30,000 IU of oral vitD3 wkly (vitD arm) or matched placebos (PL arm) for 24 weeks. The following were assessed at baseline, 12 wks, and 24 wks (end of study): 1) 25OHD levels, 2) symptoms tools (BFI – Brief Fatigue Inventory, HAQII - Health Assessment Questionnaire II, Qualitative Joint Pain (none, mild, moderate, severe), BPI – Brief Pain Inventory) and 3) hand grip strength with a dynamometer. Results: 160 women (80/arm) were enrolled from 4/09 to 7/10. There were no differences between the two arms in demographics/tumor characteristics. Median age was 61, median BMI was 29.8 kg/m2. 43% had adjuvant chemotherapy. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 wks and 31 at 24 wks in the PL arm and 22, 53 and 57 in vitD arm. One patient in the PL arm developed mild hypercalcemia. There were no SAEs. 147 subjects were evaluable for efficacy. 3 subjects, all in the PL arm discontinued early due to a MS adverse event. At wk 24, a higher proportion of women in PL (51%) vs vitD arm (37%) had a protocol defined MS event (worsening of joint pain, disability from joint pain or discontinuation of Letrozole due to MS symptoms) (p=0.069). A significantly higher proportion of women in PL (72%) vs vitD arm (42%) had an adverse QOL event (worsening of pain, disability or fatigue) (p=<0.001). Conclusions: 30,000 IU/week of vitamin D3 is safe and results in decreased adverse QOL events from adjuvant aromatase inhibitors in women with breast cancer.

Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole. The VITAL trial

2017 ◽  
Vol 166 (2) ◽  
pp. 491-500 ◽  
Author(s):  
Qamar J. Khan ◽  
Bruce F. Kimler ◽  
Pavan S. Reddy ◽  
Priyanka Sharma ◽  
Jennifer R. Klemp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Trial ◽  
Vitamin D3 ◽  
Musculoskeletal Symptoms

scholarly journals Further Evidence That OPG rs2073618 Is Associated With Increased Risk of Musculoskeletal Symptoms in Patients Receiving Aromatase Inhibitors for Early Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel L. Hertz ◽  
Karen Lisa Smith ◽  
Yuhua Zong ◽  
Christina L. Gersch ◽  
Andrea M. Pesch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Aromatase Inhibitors ◽  
Joint Pain ◽  
Musculoskeletal Symptoms ◽  
Primary Analysis ◽  
T Score ◽  
Point Increase ◽  
Increased Risk ◽  
Pain Question

BackgroundAromatase inhibitors (AI) reduce recurrence and death in patients with early-stage hormone receptor-positive (HR +) breast cancer. Treatment-related toxicities, including AI-induced musculoskeletal symptoms (AIMSS), are common and may lead to early AI discontinuation. The objective of this study was to replicate previously reported associations for candidate germline genetic polymorphisms with AIMSS.MethodsWomen with stage 0-III HR + breast cancer initiating adjuvant AI were enrolled in a prospective clinic-based observational cohort. AIMSS were assessed by patient-reported outcomes (PRO) including the PROMIS pain interference and physical function measures plus the FACT-ES joint pain question at baseline and after 3 and 6 months. For the primary analysis, AIMSS were defined as ≥ 4-point increase in the pain interference T-score from baseline. Secondary AIMSS endpoints were defined as ≥ 4-point decrease in the physical function T-score from baseline and as ≥ 1-point increase on the FACT-ES joint pain question from baseline. The primary hypothesis was that TCL1A rs11849538 would be associated with AIMSS. Twelve other germline variants in CYP19A1, VDR, PIRC66, OPG, ESR1, CYP27B1, CYP17A1, and RANKL were also analyzed assuming a dominant genetic effect and prespecified direction of effect on AIMSS using univariate logistic regression with an unadjusted α = 0.05. Significant univariate associations in the expected direction were adjusted for age, race, body mass index (BMI), prior taxane, and the type of AI using multivariable logistic regression.ResultsA total of 143 participants with PRO and genetic data were included in this analysis, most of whom were treated with anastrozole (78%) or letrozole (20%). On primary analysis, participants carrying TCL1A rs11849538 were not more likely to develop AIMSS (odds ratio = 1.29, 95% confidence interval: 0.55–3.07, p = 0.56). In the statistically uncorrected secondary analysis, OPG rs2073618 was associated with AIMSS defined by worsening on the FACT-ES joint pain question (OR = 3.33, p = 0.004), and this association maintained significance after covariate adjustment (OR = 3.98, p = 0.003).ConclusionCarriers of OPG rs2073618 may be at increased risk of AIMSS. If confirmed in other cohorts, OPG genotyping can be used to identify individuals with HR + early breast cancer in whom alternate endocrine therapy or interventions to enhance symptom detection and implement strategies to reduce musculoskeletal symptoms may be needed.

scholarly journals Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1992
Author(s):  
Max Seidensticker ◽  
Matthias Philipp Fabritius ◽  
Jannik Beller ◽  
Ricarda Seidensticker ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Disease ◽  
Positive Impact ◽  
Metastatic Breast ◽  
Normal Liver ◽  
Liver Parenchyma ◽  
Breast Cancer Patients ◽  
Radiation Induced ◽  
The Impact

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

scholarly journals Randomized Exercise Trial of Aromatase Inhibitor–Induced Arthralgia in Breast Cancer Survivors

2015 ◽  
Vol 33 (10) ◽  
pp. 1104-1111 ◽  
Author(s):  
Melinda L. Irwin ◽  
Brenda Cartmel ◽  
Cary P. Gross ◽  
Elizabeth Ercolano ◽  
Fangyong Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Strength Training ◽  
Aerobic Exercise ◽  
Usual Care ◽  
Repeated Measures ◽  
Joint Pain ◽  
Breast Cancer Survivors ◽  
Pain Scores ◽  
The Impact

Purpose Arthralgia occurs in up to 50% of breast cancer survivors treated with aromatase inhibitors (AIs) and is the most common reason for poor AI adherence. We conducted, in 121 breast cancer survivors receiving an AI and reporting arthralgia, a yearlong randomized trial of the impact of exercise versus usual care on arthralgia severity. Patients and Methods Eligibility criteria included receiving an AI for at least 6 months, reporting ≥ 3 of 10 for worst joint pain on the Brief Pain Inventory (BPI), and reporting < 90 minutes per week of aerobic exercise and no strength training. Participants were randomly assigned to exercise (150 minutes per week of aerobic exercise and supervised strength training twice per week) or usual care. The BPI, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, and Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were completed at baseline and at 3, 6, 9, and 12 months. Intervention effects were evaluated using mixed-model repeated measures analysis, with change at 12 months as the primary end point. Results Over 12 months, women randomly assigned to exercise (n = 61) attended 70% (± standard deviation [SD], 28%) of resistance training sessions and increased their exercise by 159 (± SD, 136) minutes per week. Worst joint pain scores decreased by 1.6 points (29%) at 12 months among women randomly assigned to exercise versus a 0.2-point increase (3%) among those receiving usual care (n = 60; P < .001). Pain severity and interference, as well as DASH and WOMAC pain scores, also decreased significantly at 12 months in women randomly assigned to exercise, compared with increases for those receiving usual care (all P < .001). Conclusion Exercise led to improvement in AI-induced arthralgia in previously inactive breast cancer survivors.

Relevance of Aromatase Inhibitors in Breast Cancer Treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Ankita Sood ◽  
Damanpreet Kaur Lang ◽  
Rajwinder Kaur ◽  
Balraj Saini ◽  
Sandeep Arora
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Breast Tissue ◽  
Positive Impact ◽  
Treatment Options ◽  
Living Standards ◽  
Efficacious Treatment ◽  
Clinical Resistance ◽  
Steroidal Aromatase Inhibitors ◽  
Near Future

: Efficacious treatment for breast cancer is still a challenge despite the presence of various treatment options. Aromatase enzyme present in the breast tissue is responsible for estrogen formation from androgens. Aromatase inhibitors manifest remarkably ameliorated therapeutic efficacy as compared to the current therapeutic options available and exhibit a better safety profile as compared to the other drugs. Clinical resistance to aromatase inhibitors is perceived as a lack of growth inhibition by aromatase inhibitors treatment and cancer therapy becomes ineffective in causing a decrease in the size of the tumor. Naturally extracted aromatase inhibitors have a huge positive impact on vitality and living standards. This review article highlights the particulars about the currently approved steroidal and non-steroidal aromatase inhibitors for clinical use, adverse effects associated with their use and approach to tackling the problem, various strategies to overcome aromatase inhibitors resistance, information on the synthesis of various peculiar aromatase inhibitors which can prove as highly efficient and potent drugs in the near future and the drugs of natural and semi-synthetic origin which can demonstrate to be more efficient, potent and less-toxic than conventional therapy.

Long-term results from a randomized blinded sham- and waitlist-controlled trial of acupuncture for joint symptoms related to aromatase inhibitors in early stage breast cancer (S1200).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12018-12018
Author(s):  
Dawn L. Hershman ◽  
Joseph M. Unger ◽  
Heather Greenlee ◽  
Jillian Capodice ◽  
Danika Lew ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Early Stage ◽  
Short Form ◽  
Controlled Trial ◽  
Musculoskeletal Symptoms ◽  
Long Term Results ◽  
Common Side Effect ◽  
Multicenter Randomized Controlled Trial ◽  
Joint Symptoms

12018 Background: Musculoskeletal symptoms are the most common side effect of aromatase inhibitors (AIs) among breast cancer (BC) survivors. We previously reported that true acupuncture (TA) resulted in better pain outcomes than either sham acupuncture (SA) or wait-list controls (WC) at 6 weeks with durable effects through 24 weeks, with minimal toxicity. We now report the 52-week outcomes. Methods: We conducted a SWOG multicenter randomized controlled trial among postmenopausal women with early-stage BC. Patients taking an AI for ≥30 days and reporting a worst pain score of ≥3 out of 10 using the Brief Pain Inventory-Worst Pain (BPI-WP) were eligible. Subjects were randomized 2:1:1 to TA vs. SA vs. WC. Both the TA and SA protocols consisted of a 12-week intervention, with 2 sessions per week for 6 weeks, followed by 1 session per week for 6 additional weeks. At 24 weeks, all subjects remained blinded to intervention arm but were offered 10 sessions of true acupuncture. Endpoints included BPI scores, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for hips and knees, the Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH), PROMIS Pain Inventory Short Form (PI-SF), and Functional Assessment of Cancer therapy Endocrine Symptoms (FACT-ES). Results: Among 226 patients registered, 110 were randomized to TA, 59 to SA and 57 to WC. Baseline characteristics were similar among the arms. At 52 weeks, follow-up assessments were available for 91 (82.7%) TA, 53 (89.8%) SA, and 47 (82.5%) WC patients. In a linear regression adjusting for the baseline score and stratification factors, 52-week mean BPI-WP scores were 1.08 points lower (correlating with less pain) in the TA compared to SA arm (95% CI: 0.24-1.91, p =.01), and were 0.99 points lower in the TA compared to WC arm (95% CI: 0.12-1.86, p =.03). The proportion of patients experiencing a clinically meaningful (>2) reduction (i.e. improvement) in BPI-WP was 64% for TA compared to 45% on SA and 53% on WC. Patients randomized to TA had reduced BPI pain interference at 52 weeks compared to SA (adjusted difference = 0.58, 95% CI: 0.00-1.16, p =.05) but not compared to WC (adjusted difference = 0.33, 95% CI: -0.28-0.93, p =.29). Also, at 52 weeks, patients randomized to TA had improved PROMIS PI-SF T-scores compared to SA (adjusted difference = 2.35, 95% CI: 0.07-4.63, p =.04) but not compared to WC (adjusted difference = 1.28, 95% CI: -1.09-3.66, p =.29). No statistically significant differences were observed in other measures. Conclusions: Women with breast cancer receiving AI therapy and treated with 12 weeks of TA for joint symptoms had reduced levels of worst pain compared to control patients, an effect that was durable through one year despite completion of protocol acupuncture at 12 weeks, and the offering of acupuncture to all participants at 24 weeks. Clinical trial information: NCT01535066.

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