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.

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.

Management of side effects of aromatase inhibitors (AIs) during adjuvant therapy for postmenopausal women with HR+ breast cancer: Analysis of French practices

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11593-e11593
Author(s):  
J. P. Guastalla ◽  
Y. Belkacemi ◽  
B. Cutuli ◽  
P. Dalivoust ◽  
N. Dohollou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Adjuvant Therapy ◽  
Aromatase Inhibitors ◽  
Joint Pain ◽  
Care Physician ◽  
Cancer Management ◽  
Lipid Disorders ◽  
Increased Risk

e11593 Background: Aromatase inhibitors (AIs) are widely used as adjuvant therapy for HR+ breast cancer. Most frequently reported side effects are joint pain, osteoporosis and lipid disorders. Our aim was to describe how physicians in their clinical practice manage these side effects at initiation of treatment and during follow-up. Methods: Multicentric survey conducted in October 2008 by Internet among a sample of 293 physicians specialized in breast cancer management prescribing adjuvant AIs in post-menopausal women with HR+ breast cancer Results: At initiation of AI treatment, 97 % of the physicians interviewed declared informing their patients of the possible occurrence of joint pain; corresponding figures were 81 % for the increased risk of osteoporotic fractures, 66 % for lipid disorders, 59 % for asthenia, and only 16% for cognitive disorders. At initiation, 71% of the physicians assess fracture history, 83 % prescribe BMD, and 60 % lipid tests. Co-prescription of drugs in association with AIs from the onset of treatment is uncommon (24% of physicians interviewed), vitamin D and calcium being the most frequent prescription (19%); prescription of bisphosphonates was less frequently declared (10%). During the course of treatment, 90% of physicians assess BMD at least once, 41% repeat BMD two years after and 41% adapt monitoring of BMD according to the initial result. Lipid tests are monitored every six months by 29% of physicians, and every year by 29%. In case of joint pain, the initial therapeutic management includes: prescription of an analgesic and/or an anti-inflammatory for 66% of physicians, change of AI for 28%; the switch for tamoxifene is mentioned by only 1%. As a second step in case of failure of the initial measures, adjuvant treatment is modified by 70 % of physicians: change of AI by 50 %, switch for tamoxifene by 20 %. Conclusions: The possible side effects of aromatase inhibitors are taken into account by physicians from the initiation of treatment. They perform themselves the monitoring of the patient during follow-up, including the search for side effects. Bone-joint adverse events are managed by oncologists while the care of lipid disorders is transferred to the primary care physician. No significant financial relationships to disclose.

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.

PTHrP(12-48) for the diagnosis of breast cancer bone metastasis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21039-e21039
Author(s):  
Charity L. Washam ◽  
Stephanie D. Byrum ◽  
Kim Leitzel ◽  
Ali M. Suhail ◽  
Allan Lipton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
Parathyroid Hormone Related Protein ◽  
Increased Risk ◽  
Breast Cancer Bone Metastasis

e21039 Background: Bone metastasis of breast cancer significantly compromises patient morbidity and mortality. Currently, no reliable methods detect or predict patients at increased risk for developing bone metastasis. We utilized 3 independent cohorts of breast cancer patients to validate a highly discriminatory plasma-based proteomic profile that identifies breast cancer bone metastasis. The identity of the most discriminatory protein component identified was a parathyroid hormone-related protein fragment, PTHrP(12-48). Methods: Plasma samples collected from 21 breast cancer patients with clinical evidence of a bone metastasis and 21 patients with no evidence of bone metastasis from time of diagnosis to clinical outcome were evaluated. A novel mass spectrometry-based assay using human serum spiked with synthetic PTHrP(12-48) was used to measure PTHrP(12-48) concentrations (pg/μl). Statistical significance was assessed by one-way ANOVA. ROC curves evaluated the diagnostic potential of PTHrP(12-48) and a simple logistic regression derived from the combined measurement of PTHrP(12-48) and NTx. Results: PTHrP(12-48) concentrations ranged between 11.6 and 92.1 pg/μl in bone metastasis patients and between 4.5 and 34.2 pg/μl in patients without bone metastases. PTHrP(12-48) was significantly increased in bone metastasis plasma (p < 0.05). No significant correlation was identified between PTHrP(12-48) and NTx. ROC analysis of PTHrP(12-48), threshold 18 pg/μl, classified the two groups with high accuracy. Class prediction by the PTHrP(12-48)/NTx logistic regression model increased diagnostic specificity. Conclusions: The measurement of PTHrP(12-48) in patient plasma has potential as a viable clinical measure of bone metastasis. In combination with serum NTx, PTHrP(12-48) may assist in identifying bone metastases in patients presenting with low to normal bone turnover markers.

Risk factors for fractures in patients on hormonal therapies for breast cancer and DCIS.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19627-e19627
Author(s):  
Abdullah Ladha ◽  
Josy Mathew
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Bone Mineral Density ◽  
Aromatase Inhibitors ◽  
Hormonal Therapy ◽  
Mineral Density ◽  
Risk Of Fracture ◽  
Increased Risk ◽  
Hormonal Therapies ◽  
Positive Breast Cancer

e19627 Background: Hormonal therapy with aromatase inhibitors (AI) or tamoxifen (TAM) is standard of care for hormone receptor positive breast cancer and DCIS. Fractures are a complication of treatment with AI due to accelerated bone loss. Risk factors for fracture in patients on hormonal therapy (HT) for breast cancer and DCIS are poorly defined. Methods: All 71 patients with breast cancer or DCIS seen in the bone and mineral clinic of our institution from 2000 to 2010 were analyzed. Data on demographics, pathology, type and duration of HT, bone mineral density studies (BMD), number and site of fractures were collected. Statistical analysis: t test, chi square test and Fisher’s exact test for categorical data. Results: The age of the patients ranged 40 to 97 years. 65 patients had ER positive breast cancer, 6 patients had DCIS. 9 patients had fractures.41 patients were on an AI alone, 8 were on TAM alone and 14 were on both sequentially. Fractures involved: vertebral compression, femur, hip, distal radioulnar, rib, hand and feet bones. Patients who had osteoporosis at the femur, osteoporosis or osteopenia in the lumbar spine or forearm in the initial BMD study were found to have an increased risk of fracture (P<0.05). Patients who were on TAM and AI sequentially had an increased risk of fracture (P<0.05) compared AI alone. The use of bisphosphonates and the duration of use were significantly associated with fracture (P<0.05) as these patients already had osteoporosis. The age, race, duration of AI use and the use of calcium and vitamin D were not found to be significantly different in patients who had fractures compared to those who did not. In the 24 patients who had two BMD studies, there was no significant change in the BMD overall. Conclusions: Patients with osteoporosis or osteopenia at baseline have an increased risk of fracture with the use of hormonal therapies for breast cancer and DCIS. This risk was not eliminated by the use of bisphosphonates. Sequential use of tamoxifen and aromatase inhibitors increase the risk of fractures. Bone mineral density studies done prior to the initiation of hormonal therapy for breast cancer maybe useful estimating the risk of fracture while on treatment.

scholarly journals Anastrozole-Induced Carpal Tunnel Syndrome: Results From the International Breast Cancer Intervention Study II Prevention Trial

2016 ◽  
Vol 34 (2) ◽  
pp. 139-143 ◽  
Author(s):  
Francesco Spagnolo ◽  
Ivana Sestak ◽  
Anthony Howell ◽  
John F. Forbes ◽  
Jack Cuzick
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Carpal Tunnel Syndrome ◽  
Carpal Tunnel ◽  
Odds Ratio ◽  
Intervention Study ◽  
Musculoskeletal Symptoms ◽  
Increased Risk ◽  
Tunnel Syndrome ◽  
Cancer Intervention

Purpose Carpal tunnel syndrome (CTS) occurs when the median nerve is compressed at the wrist in the carpal tunnel. It has been suggested that hormonal risk factors may be involved in the pathogenesis of CTS, and a higher incidence of CTS has been reported in randomized clinical trials with aromatase inhibitors (AIs) compared with tamoxifen. Patients and Methods This was an exploratory analysis of the International Breast Cancer Intervention Study II, a double-blind randomized clinical trial in which women at increased risk of breast cancer were randomly assigned to receive anastrozole or placebo. This is the first report of risk factors for and characteristics of CTS in women taking an AI in a placebo-controlled trial. Results Overall, 96 participants with CTS were observed: 65 (3.4%) in the anastrozole arm and 31 (1.6%) in the placebo arm (odds ratio, 2.16 [1.40 to 3.33]; P < .001). Ten participants were reported as having severe CTS, of which eight were taking anastrozole (P = .08). Eighteen women (0.9%) in the anastrozole arm and six women (0.3%) in the placebo arm reported surgical intervention, which was significantly different (odds ratio, 3.06 [1.21 to 7.72], P = .018). Six women discontinued with the allocated treatment because of the onset of CTS. Apart from treatment allocation, a high body mass index and an a prior report of musculoskeletal symptoms after trial entry were the only other risk factors for CTS identified in these postmenopausal women. Conclusions The use of anastrozole was associated with a higher incidence of CTS but few participants required surgery. Further investigations are warranted into the risk factors and treatment of AI-induced CTS.

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