Background Aromatase inhibitors (AI) are widely used in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. The onset of musculoskeletal symptoms related to AI therapy limits the treatment compliance.

Objectives To evaluate the incidence and the clinical presentation of musculoskeletal syndromes and the prevalence of autoantibodies during AI therapy.

Methods We enrolled 49 consecutive postmenopausal patients with non-metastatic breast cancer treated with third generation AI for at least three months (AI+ group) and 10 postmenopausal controls with breast cancer in adjuvant therapy but not treated with AI (AI- group). The two groups were evaluated with a rheumatological examination (tender and swollen joint count, tender points, CDAI), with PRO-CLARA, FACIT-fatigue and HAQ questionnaires and ANA, ENA screen and ACPA dosage. ANA were assayed in indirect immunofluorescence on Hep-2 cells using as a cut-off a dilution of 1:80; ENA screen and ACPA were assayed with ELISA commercial kits.

Results The mean ages were 62.6±9 years for AI+ group and 58±11.8 years for AI- group (p=0.2, U=140.5). In AI+ group, 27 (55%) patients exhibited at least one tender joint and 15 (30%) patients exhibited at least one swollen joint. In AI- group, two patients exhibited at least one tender joint and one patient exhibited at least one swollen joint. 22% of AI+ group patients and 20% of AI- group patients showed more than 11 tender points (TP). When patients with more than 11 TP positivity were excluded from the analysis, tender joint count was more higher in AI+ group (p=0.037). Differences between AI+ and AI- groups regarding PRO-CLARA, FACIT-fatigue, HAQ and CDAI were summarized in Tab. 1. In AI+ group, PRO-CLARA values correlates with FACIT-fatigue values (R=-0.59, p<0.0001), swollen joint count (R=0.48, p=0.001), tender joint count (R=0.72, p<0.0001), tender points count (R=0.76, p<0.0001), HAQ values (R=0.85, p<0.0001), CDAI values (R=0.89, p<0.0001) and does not correlate with the age of the patients. 67% of the AI+ group patients showed ANA positivity vs 20% AI- group patients (p 0.01, RR 3.3).

Conclusions In this preliminary study, we demonstrated a higher prevalence of arthralgia/arthritis in AI+ group than in AI- group. No significant difference in tender points count was detected between the two groups. In AI+ group, higher values of PRO-CLARA, HAQ and CDAI than those of AI- group were showed. A higher rate of ANA positivity was demonstrated in AI+ group. These results support the hypothesis of a possible role of an immune system dysregulation in the development of musculoskeletal syndromes during AI therapy. The expertise of a rheumatologist could help patients with estrogen receptor-positive breast cancer treated with AI to improve their quality of life and to ensure a greater compliance to AI therapy.

References

1. Lønning PE, et al. Endocr Relat Cancer. 2013 Jun 24;20(4):R183-201.

2. Niravath P. Ann Oncol. 2013 Jun;24(6):1443-9.

3. Shanmugam VK, et al. Breast Cancer Res Treat. 2012 Jan;131(2):699-708.

Disclosure of Interest None declared