LETROZOLE IMPROVES PROGRESSION-FREE SURVIVAL OF POSTMENOPAUSAL PATIENTS WITH ADVANCED BREAST CANCER TREATED WITH PEGYLATED LIPOSOMAL DOXORUBICIN AND MAGNETOTHERMY
DOI:
https://doi.org/10.15407/exp-oncology.2025.03.356Keywords:
advanced postmenopausal breast cancer, drug resistance, pegylated liposomal doxorubicin, mild magnetothermy, survivalAbstract
Background. Resistance of the advanced breast cancer (aBC) to hormone therapy and chemotherapy due to hyperactivated PI3K-pathway caused by mutations in the PIK3CA gene is a major treatment problem. Combining pegylated liposomal doxorubicin (PLD) with mild magnetothermy (MT) and letrozole could improve the efficacy of treatment. The aim was to assess the effect of combined treatment with PLD, MT, and letrozole on the survival of patients with luminal B postmenopausal aBC with mutations in the PIK3CA gene. Material and Methods. The aBC postmenopausal patients who progressed on a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and an aromatase inhibitor (AI) or neoadjuvant chemotherapy (ACT) were included in the study. Group 1 included 20 patients, treated with PLD + MT every 28 days (4 courses) and letrozole (daily per os, 4 months). Group 2 included 20 patients, who received the same treatment without letrozole. By PIK3СА status, each group included 10 patients with a mutant PIK3СА and 10 patients with a wild-type gene. Results. Application of PLD + MT in combination with letrozole demonstrated improved progression-free survival (PFS) compared to PLD + MT alone. In group 1, the median PFS was 10.6 months (95% CI, 7.4—11.9 months) compared to a median PFS of 8.9 months (95% CI, 6.1—9.7 months) in group 2 (p = 0.005). In the sensitivity analyses, PFS of patients with wild-type PIK3CA in the first cohort was 10.1 months (95% CI, 8.7—11.1 months) compared to 8.4 months (95% CI, 7.0—10.4 months) in groups 1 and 2 respectively (p = 0.004), by 1:1 greedy nearest neighbor matching. Conclusion. PLD with local MH in combination with letrozole was more effective irrespective of the PIK3CA gene status in postmenopausal aBC patients.
References
Subhan M, Parveen f, Shah h, et al. Recent advances with precision medicine treatment for breast cancer including triple-negative sub-type. Cancers (Basel). 2023;15(8):2204. https://doi.org/10.3390/cancers15082204
Emran T, Shahriar A, Mahmud A, et al. Multidrug resistance in cancer: Understanding molecular mecha- nisms, immunoprevention and therapeutic approaches. Front Oncol. 2022;12:891652. https://doi.org/10.3389/ fonc.2022.891652
Globus O, Greenhouse I, Sella T, et al. The neoadjuvant systemic treatment of early breast cancer: a narrative review.
Ann Breast Surg. 2023;7:39. https://doi.org/10.21037/abs-21-109
Bertucci A, Bertucci f, Gonçalves A. Phosphoinositide 3-kinase (PI3K) inhibitors and breast cancer: An overview of current achievements. Cancers (Basel). 2023;15(5):1416. https://doi.org/10.3390/cancers15051416
Ben Rekaya M, Sassi f, Saied E, Bel haj Kacem L. PIK3CA mutations in breast cancer: A Tunisian series. PLoS One. 2023;18(5):e0285413. https://doi.org/10.1371/journal.pone.0285413
Zhou d, Ouyang Q, Liu L, et al. Chemotherapy modulates endocrine therapy-related resistance mutations in meta- static breast cancer. Transl Oncol. 2019;12(5):764-774. https://doi.org/10.1016/j.tranon.2019.02.014
Movchan OV, Smolanka II, Lyashenko AO, et al. Pegylated liposomal doxorubicin for PIK3CA “wild”, hR+, hER2-, chemoresistant advanced breast cancer. Onkologia Radioterapia. 2025;19(5):1-5.
Regenold M, Kaneko K, Wang X, et al. Triggered release from thermosensitive liposomes improves tumor targeting of vinorelbine. J Control Release. 2023;354:19-33. https://doi.org/10.1016/j.jconrel.2022.12.010
Orel VE, Shevchenko Ad, Bogatyreva GP, et al. Magnetic characteristics and anticancer activity of a nanocom- plex consisting of detonation nanodiamond and doxorubicin. J Superhard Mater. 2012;34(3):179-185. https://doi. org/10.3103/S1063457612030057
Malik J, Ahmed S, Jan B, et al. drugs repurposed: An advanced step towards the treatment of breast cancer and challenges. Biomed Pharmacother. 2022;145:112375. https://doi.org/10.1016/j.biopha.2021.112375
Teomete M, Cabuk d, Korkmaz T, et al. Recommendations for cyclin-dependent kinase 4/6 inhibitor treatments in the context of co-morbidity and drug interactions (Review). Oncol Lett. 2024;27:145. https://doi.org/10.3892/ ol.2024.14278
Cerma K, Piacentini f, Moscetti L, et al. Targeting PI3K/AKT/mTOR pathway in breast cancer: from biology to clinical challenges. Biomedicines. 2023;11(1):109. https://doi.org /10.3390/biomedicines11010109
Sirico M, d’Angelo A, Gianni C, et al. Current state and future challenges for pi3k inhibitors in cancer therapy.
Cancers (Basel). 2023;15(3):703. https://doi.org/10.3390/cancers15030703
Loboda A, Smolanka I Sr, Orel VE, et al. Efficacy of combination neoadjuvant chemotherapy and regional inductive moderate hyperthermia in the treatment of patients with locally advanced breast cancer. Technol Cancer Res Treat. 2020;19:1533033820963599. https://doi.org/10.1177/1533033820963599
Li y, Qi L, Wang y, et al. A multicenter randomized trials to compare the bioequivalence and safety of a generic doxo- rubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer. Front Oncol. 2022;12:1070001. https://doi.org/10.3389/fonc.2022.1070001
Tang L, he M, Wu J et al. et al. Cardiac safety and efficacy for patients with early-stage breast cancer treated with pegylated liposomal doxorubicin (PLd) or doxorubicin. J Clin Oncol. 2023;41:550-550. https://doi.org/10.1200/ JCO.2023.41.16_suppl.550
Klimanov Myu, Syvak LA, Orel VE, et al. Efficacy of combined regional inductive moderate hyperthermia and chemotherapy in patients with multiple liver metastases from breast cancer. Technol Cancer Res Treat. 2018;17:1-7. https://doi.org/10.1177/1533033818806003
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Experimental Oncology

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
