Differentiated approach to adjuvant neutron therapy in patients with locally advanced breast cancer, taking into account signifcant prognostic factors

The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy.
Material and Methods. The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer.
Results. A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ² =43.7; p<0.001). The sensitivity of the model was 87.1 %, the specifcity was 85.7 %, and the diagnostic accuracy was 86.4 %. We present a clinical case with an estimated risk of developing local recurrence of breast cancer of 99 %. A patient received adjuvant neutron therapy, which made it possible to avoid the development of recurrence. At 5 years of follow-up after combined treatment modality including neutron therapy to the postoperative scar area, no evidence of local recurrence was found.
Conclusion. Based on the data obtained, the approach to indications for adjuvant neutron therapy, namely: stage III B-C breast cancer, tumor invasion into the dermis, angiolymphatic invasion, grade 3 tumor, triple-negative tumor subtype and overexpression Her2-neu subtype. 

1. Cancer Incidence in Five Continents. Vol. XI. Ed. by Bray F., Colombet M., Mery L., Piñeros M., Znaor A., Zanetti R., Ferlay J. Lyon: International Agency for Research on Cancer. 2021; 166: 1545.

2. Malignant tumors in Russia in 2019 (morbidity and mortality). Ed. by A.D. Kaprin, V.V. Starinsky, A.O. Shahzadova. Moscow, 2020. 252 p. (in Russian).

3. Khaylenko V.A., Komov D.V. Oncomammology. Moscow, 2015. 328 p. (in Russian).

4. Vtorushin S.V., Krahmal N.V., Zavyalova M.V. Triple-negative breast cancer. Modern molecular genetic concepts and their clinical signifcance. Arkhiv patologii. 2021; 83(2): 4651. (in Russian). doi: 10.17116/patol20218302146.

5. Startseva Zh.A., Simonov K.A., Slonimskaya E.M. Selection of the optimal volume of irradiation in breast cancer patients in accordance with signifcant predictors. Problems in Oncology. 2015; 61(5): 778–81. (in Russian).

6. Zenzola V., Cabezas-Quintario M.A., Arguelles M., Pérez-Fernández E., Izarzugaza Y., Correa A., García-Foncillas J. Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer. Clin Transl Oncol. 2018; 20(11): 1448–54. doi: 10.1007/s12094-018-1877-5.

7. Simonov K.A., Startseva Zh.A., Slonimskaya E.M., Musabaeva L.I., Doroshenko A.V. Method for prediction of local postoperative recurrences in patients with breast cancer. The patent of the Russian Federation No. 2540168 RU, Int. Cl. A61 B 5/00. No. 2014105803/14. 10.02.2015, Bull. No. 4. (in Russian).

8. Yang P.S., Chen C.M., Liu M.C., Jian J.M., Horng C.F., Liu M.J., Yu B.L., Lee M.Y., Chi C.W. Radiotherapy can decrease locoregional recurrence and increase survival in mastectomy patients with Tl to T2 breast cancer and one to three positive nodes with negative estrogen receptor and positive lymphovascular invasion status. Int J Radiat Oncol Biol Phys. 2010; 77(2): 516–22. doi: 10.1016/j.ijrobp.2009.05.016.

9. Semiglazov V.F., Paltuev R.M., Semiglazov V.V. General recommendations for the management of breast cancer (St. Gallen Expert Consensus developed at the 16th International Breast Cancer Conference). Tumors of Female Reproductive System. 2019; 15(4): 50–7. (in Russian). doi: 10.17650/1994-4098-2019-15-4-50-57.

10. Laurberg T., Alsner J., Tramm T., Jensen V., Lyngholm C.D., Christiansen P.M., Overgaard J. Impact of age, intrinsic subtype and local treatment on long-term local-regional recurrence and breast cancer mortality among low-risk breast cancer patients. Acta Oncol. 2017; 56(1): 59–67. doi: 10.1080/0284186X.2016.1246803.

11. Alabdulkareem H., Pinchinat T., Khan S., Landers A., Christos P., Simmons R., Moo T.A. The impact of molecular subtype on breast cancer recurrence in young women treated with contemporary adjuvant therapy. Breast J. 2018; 24(2): 148–53. doi: 10.1111/tbj.12853.

12. Startseva Zh.A., Simonov K.A., Slonimskaya E.M. Differentiated approach to the use of adjuvant radiation therapy for patients with operable breast cancer. Radiation and Risk. 2014; 23 (2): 102–11. (in Russian).

13. Chen Q.X., Wang X.X., Lin P.Y., Zhang J., Li J.J., Song C.G., Shao Z.M. The diferent outcomes between breast-conserving surgery and mastectomy in triple-negative breast cancer: a population-based study from the SEER 18 database. Oncotarget. 2017; 8(3): 4773–80. doi: 10.18632/oncotarget.13976.

14. Velikaya V.V., Startseva Zh.А, Lisin V.А., Simonov К.А., Popova N.O., Goldberg V.E. complex using in patients Late efects of combined modality treatment with adjuvant neutron therapy for locally advanced breast cancer. Radiation and Risk. 2018; 27(1): 107–14. (in Russian). doi: 10.21870/0131-3878-2018-27-1-107-114.