Background Autoimmune disorders (AD) and conditions requiring immunosuppressive therapy are potential comorbidities in long-term breast cancer (BC) survivors, and may have some impact on the treatment of late relapses with immunotherapy and/or standard targeted therapy with cyclin-dependent kinase inhibitors (CDKI) or anti-human epidermal receptor-2 monoclonal antibodies (Her2MoAbs) .

Methods Study population consisted of BC patients with at least 10 years of follow-up who started or continued previous therapy with CDKI or Her2MoAbs for relapsed disease in a single academic institution (2018–2022). This observational study was approved by the Navarre Regional Ethics Board, approval number: 2018/92.

Results 122/2,592 long-term BC survivors fulfilled the selection criteria. Treatment: 83 CDKI (81 palbociclib, 2 ribociclib), 39 Her2MoAbs (trastuzumab and or/sequences with pertuzumab, trastuzumab emtansine or trastuzumab deruxtecan). Median age: 64.6 years (44–84). Median follow-up after initial BC diagnosis: 16.3 years (10–43). Median therapy duration for CDKI: 16.7 months (1–61), and for Her2MoAbs: 58.3 months (3–182). Median follow-up after the start of CDKI: 28 months (1–61) and for Her2MoAbs: 65 months (3–182). 17/83 (20.4%) patients treated with CDKI had a previous diagnosis of AD (10 thyroid autoimmune disease, 3 autoimmune gastritis, 1 myasthenia gravis, 1 ulcerative colitis, 1 Crohn disease, 1 psoriatic arthritis plus gastritis and thyroid disease). No cases of new AD ocurred during or after therapy with CDKI but 1/10 patients with thyroid AD had an impairment in thyroid function and 1 patient with autoimmune gastritis developed inflammatory lung disease. 6/39 (15.8%) patients treated with Her2 MoAbs had AD (5 previous diagnoses of thyroid autoimmune disease, 1 developed seronegative rheumatoid arthritis during the Her2MoAb treatment). Several immunosuppressive drugs and inflammatory response modifiers were used in one patient with psoriatic arthritis on ongoing treatment with palbociclib (prednisone, rituximab, sulfasalazine, leflunomide, apremilast, methotrexate) without complications, and tumor response maintained at 24 months. Response is also maintained at 29 months in one patient on palbociclib who needed a change of immunosuppressive therapy from adalimumab to ustekinumab, with good tolerance. Clinical benefit and good tolerance were also found on 2 patients on concurrent treatment with mesalazine.

Conclusions Autoimmune disorders are relatively common in long-term BC survivors who needed therapy with CDKI or Her2MoAbs for late relapses. No special challenges were found in the management of these patients and a judicious use of immunosuppressive therapy had no apparent impact on the tolerance and antitumor effect of CDKI therapy in this cohort.

Ethics Approval Approved by the Comité de Etica de Investigación con Medicamentos de Navarra, Pyto 2018/92.

Code ILL-CAR-2018–01.