Managing arthralgia in a postmenopausal woman taking an aromatase inhibitor for hormonesensitive early breast cancer: a case study

Figures & data

Table 1 DFS benefits in selected trials of adjuvant AI therapy in postmenopausal women with HR⁺ breast cancer^{7,8,14,16–21,45}

Clinical trial	Follow-up	Treatment arms	Adjuvant setting	DFS
ATAC	68 months	Anastrozole vs tamoxifen	Initial	HR = 0.83; P = 0.005a
ATAC	100 months	Anastrozole vs tamoxifen	Initial	HR = 0.85; P = 0.003a
ATAC	120 months	Anastrozole vs tamoxifen	Initial	HR = 0.86; P = 0.003a
BIG 1–98	25.8 months	Letrozole vs tamoxifen	Initial	HR = 0.81; P = 0.003
BIG 1–98	76 months	Letrozole vs tamoxifen	Initial	HR = 0.88; P = 0.03
TEAM	2.75 years	Exemestane vs tamoxifen	Initial	HR = 0.89; P = 0.12
TEAM	5.1 years	Exemestane vs tamoxifen→exemestane	Sequential	HR = 0.97; P = 0.60b
IES	55.7 months	Exemestane vs tamoxifen	Switch	HR = 0.76; P = 0.0001
IES	91 months	Exemestane vs tamoxifen	Switch	HR = 0.84; P = 0.002
MA.17	30 months	Letrozole vs placebo	Extended	HR = 0.58; P < 0.001

Notes:

a Results for HR⁺ subpopulation;

b 5-year DFS.

Abbreviations: AI, aromatase inhibitor; ATAC, anastrozole (Arimidex), tamoxifen, alone or in combination; BIG, Breast International Group; DFS, disease-free survival; HR⁺, hormone receptor-positive; IES, Intergroup Exemestane Study; TEAM, tamoxifen exemestane adjuvant multinational.

Table 2 Studies of switching from one AI to another in postmenopausal women with HR⁺ breast cancer to address musculoskeletal symptoms

Study	N	Study design	Results	Reference
ALIQUOT	182	Open-label, crossover study 12 weeks of letrozole followed by 12 weeks of anastrozole, or 12 weeks of anastrozole followed by 12 weeks of letrozole	56% had joint problems on letrozole but not on anastrozole 55% had joint problems on anastrozole but not on letrozole	^Citation41,Citation42
ATOLL	179	Prospective, nonrandomized, open-label, multicenter study Patients who discontinued anastrozole due to musculoskeletal symptoms initiated letrozole for 6 months or until discontinuation due to intolerance or disease progression	71.5% of patients on letrozole at 6 months 28.5% discontinued due to musculoskeletal symptoms	^Citation43
Yardley et al^Citation44	261	Patients who discontinued anastrozole due to grade 2 or 3 arthralgia/myalgia initiated letrozole for 6 months	87.4% of patients on letrozole at 6 months 9.6% discontinued due to arthralgia/myalgia	^Citation44

Abbreviations: AI, aromatase inhibitor; ALIQUOT, Anastrozole versus Letrozole: Investigation into Quality of Life and Tolerability; ATOLL, Articular Tolerance of Letrozole; HR⁺, hormone receptor-positive.

Breast International Group (BIG) 1–98 Collaborative GroupThürlimannBKeshaviahAA comparison of letrozole and tamoxifen in postmenopausal women with early breast cancerN Engl J Med2005353262747275716382061

 PubMed Web of Science ®Google Scholar

BIG 1–98 Collaborative GroupMouridsenHGiobbie-HurderALetrozole therapy alone or in sequence with tamoxifen in women with breast cancerN Engl J Med2009361876677619692688

 PubMed Web of Science ®Google Scholar

HowellACuzickJBaumMATAC Trialists’ GroupResults of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancerLancet20053659453606215639680

 PubMed Web of Science ®Google Scholar

CuzickJSestakIBaumMATAC/LATTE investigatorsEffect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trialLancet Oncol201011121135114121087898

 PubMed Web of Science ®Google Scholar

GossPEIngleJNMartinoSRandomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17J Natl Cancer Inst200597171262127116145047

 PubMed Web of Science ®Google Scholar

Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ GroupForbesJFCuzickJEffect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trialLancet Oncol200891455318083636

 PubMed Web of Science ®Google Scholar

DixonJMRenshawLLangridgeCAnastrozole and letrozole: an investigation and comparison of quality of life and tolerabilityBreast Cancer Res Treat2011125374174920821047

 PubMed Web of Science ®Google Scholar

RenshawLMcHughMWilliamsLComparison of joint problems as reported by patients in a randomised adjuvant trial of anastrozole and letrozoleBreast Cancer Res Treat2007106Suppl 1S108 Abst 2072

 Google Scholar

BriotKTubiana-HulinMBastitLKloosIRouxCEffect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) studyBreast Cancer Res Treat2010120112713420035381

 PubMed Web of Science ®Google Scholar

YardleyDGreenNPapishSRheumatologic evaluation of adjuvant letrozole in post-menopausal breast cancer patients discontinuing anastrozole due to grade 2–3 arthralgia or myalgiaCancer Res20096924 Suppl 3 Abst 805

 Web of Science ®Google Scholar