Review of Current Standards and Trends in Radiation Therapy Development in Triple Negative Breast Cancer

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Abstract

This article provides a comprehensive review of current standards and promising trends in radiation therapy for triple-negative breast cancer. The latest advancements in the diagnosis and treatment of this aggressive cancer type are examined, including the implementation of advanced radiation therapy techniques such as stereotactic radiotherapy, intensity-modulated radiation therapy, and intraoperative radiation therapy. Particular attention is given to optimizing treatment regimens, reducing side effects, and improving patients’ quality of life. Various approaches to combining radiation therapy with chemotherapy, immunotherapy, and targeted therapy are discussed, along with the prospects of personalized treatment based on the molecular and genetic characteristics of tumors. The results of recent clinical trials aimed at identifying the most effective treatment strategies are analyzed. The importance of a multidisciplinary approach involving oncologists, radiologists, and other specialists is emphasized. Additionally, the impact of emerging technologies and personalized medicine on radiation therapy development is explored, including the use of artificial intelligence and biomarkers for individualized treatment selection. Furthermore, issues related to radiobiology, mechanisms of tumor cell radioresistance, and potential strategies to overcome them are discussed to enhance treatment effectiveness and improve patient outcomes in triple-negative breast cancer.

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About the authors

Olesya A. Chirkova

I.P. Pavlov Ryazan State Medical University

Author for correspondence.
Email: chirach726@gmail.com
ORCID iD: 0009-0001-5233-7196
Russian Federation, Ryazan

Alisa M. Zhukova

I.P. Pavlov Ryazan State Medical University

Email: alice-zhukova@mail.ru
ORCID iD: 0009-0009-0957-3992
Russian Federation, Ryazan

Zarina R. Nabieva

Bashkir State Medical University

Email: zarina.nabieva.0101@mail.ru
ORCID iD: 0009-0005-1121-6389
Russian Federation, Ufa

Valeria S. Degtyareva

I.M. Sechenov First Moscow State Medical University

Email: degtyareva@ya.ru
ORCID iD: 0009-0000-3834-435X

MD

Russian Federation, Moscow

Polina V. Bredikhina

Kursk State Medical University

Email: evm4662@mail.ru
ORCID iD: 0009-0001-7810-5692
SPIN-code: 4450-2105

MD

Russian Federation, Kursk

Vladislav E. Pochapskiy

Kuban State Medical University

Email: v@pochapskij.ru
ORCID iD: 0009-0000-5299-7162
Russian Federation, Krasnodar

Anna O. Golubeva

Rostov State Medical University

Email: golubevaanna092@gmail.com
ORCID iD: 0009-0003-7664-0477
Russian Federation, Rostov-on-Don

Darya A. Pavlikhina

Samara State Medical University

Email: pablo_2001@bk.ru
ORCID iD: 0009-0002-4114-2219

MD

Russian Federation, Samara

Nadezhda V. Sokolova

I.P. Pavlov First St. Petersburg State Medical University

Email: Sokolova.nadya26@yandex.ru
ORCID iD: 0009-0001-2529-061X

MD

Russian Federation, Saint Petersburg

Ekaterina Y. Chursina

I.M. Sechenov First Moscow State Medical University

Email: yekaterina3565@yandex.ru
ORCID iD: 0009-0003-5404-7576

MD

Russian Federation, Moscow

Darya D. Zykova

I.P. Pavlov First St. Petersburg State Medical University

Email: darazykova30048@gmail.com
ORCID iD: 0009-0002-4150-7134

MD

Russian Federation, Saint Petersburg

Alena O. Ivanova

I.P. Pavlov First St. Petersburg State Medical University

Email: alenaivanova0712@icloud.com
ORCID iD: 0009-0005-9744-4584

MD

Russian Federation, Saint Petersburg

Alina A. Potapova

Russian University of Medicine

Email: alina2844500@mail.ru
ORCID iD: 0009-0005-5082-1426

MD

Russian Federation, Moscow

Emomali A. Rakhimov

Ural State Medical University

Email: rahimovemomali18@mail.ru
ORCID iD: 0009-0008-0910-8858

MD

Russian Federation, Yekaterinburg

References

  1. Andreev DA, Zavyalov AA. Triple-negative breast cancer: new options for systemic targeted therapy. A review. Journal of Modern Oncology. 2022;24(3):368–372. EDN: SARUWK doi: 10.26442/18151434.2022.3.201767
  2. Vtorushin SV, Krakhmal NV, Zavyalova MV. Triple-negative breast cancer. Modern molecular genetic concepts and their clinical significance. Russian Journal of Archive of Pathology. 2021;83(2):46–51. EDN: DHFZXP doi: 10.17116/patol20218302146
  3. Smirmova OV, Borisov VI, Guens GP. Immediate and long-term outcomes of drug treatment in patients with metastatic triple negative breast cancer. Malignant tumours. 2018;8(3):68–77. EDN: KJOLFM doi: 10.18027/2224-5057-2018-8-3-68-77
  4. de Araújo RA, Cordero da Luz FA, da Costa Marinho E, et al. Operable breast cancer: How not to worsen the prognosis, especially in triple negative and stage II tumors. Surg Oncol. 2021;38:101596. doi: 10.1016/j.suronc.2021.101596
  5. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG); Darby S, McGale P, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–1716. doi: 10.1016/S0140-6736(11)61629-2
  6. Voduc KD, Cheang MC, Tyldesley S, et al. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010;28(10):1684–1691. doi: 10.1200/JCO.2009.24.9284
  7. Wang J, Xie X, Wang X, et al. Locoregional and distant recurrences after breast conserving therapy in patients with triple-negative breast cancer: a meta-analysis. Surg Oncol. 2013;22(4):247–255. doi: 10.1016/j.suronc.2013.10.001
  8. Arvold ND, Taghian AG, Niemierko A, et al. Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol. 2011;29(29):3885–3891. doi: 10.1200/JCO.2011.36.1105
  9. Gangi A, Chung A, Mirocha J, et al. Breast-conserving therapy for triple-negative breast cancer. JAMA Surg. 2014;149(3):252–258. doi: 10.1001/jamasurg.2013.3037
  10. Sjöström M, Lundstedt D, Hartman L, et al. Response to radiotherapy after breast-conserving surgery in different breast cancer subtypes in the Swedish Breast Cancer Group 91 Radiotherapy Randomized Clinical Trial. J Clin Oncol. 2017;35(28):3222–3229. doi: 10.1200/JCO.2017.72.7263
  11. Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159–182. doi: 10.1016/j.annonc.2023.11.016
  12. Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388(7):585–594. doi: 10.1056/NEJMoa2207586
  13. Hughes KS, Schnaper LA, Berry D, et al. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004;351(10):971–977. doi: 10.1056/NEJMoa040587
  14. Zhai Z, Zheng Y, Yao J, et al. Evaluation of adjuvant treatments for T1 N0 M0 triple-negative breast cancer. JAMA Netw Open. 2020;3(11):e2021881. doi: 10.1001/jamanetworkopen.2020.21881
  15. Haque W, Verma V, Hsiao KY, et al. Omission of radiation therapy following breast conservation in older (≥70 years) women with T1-2N0 triple-negative breast cancer. Breast J. 2019;25(6):1126–1133. doi: 10.1111/tbj.13443
  16. Algan O, Zhao YD, Herman T. Radiotherapy in patients 70 years and older with triple-negative breast cancer. Clin Breast Cancer. 2016;16(4):e99–e106. doi: 10.1016/j.clbc.2016.05.011
  17. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362(6):513–520. doi: 10.1056/NEJMoa0906260
  18. Offersen BV, Alsner J, Nielsen HM, et al. Hypofractionated versus standard fractionated radiotherapy in patients with early breast cancer or ductal carcinoma in situ in a randomized phase III trial: the DBCG HYPO trial. J Clin Oncol. 2020;38(31):3615–3625. doi: 10.1200/JCO.20.01363
  19. Smith BD, Bellon JR, Blitzblau R, et al. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018;8(3):145–152. doi: 10.1016/j.prro.2018.01.012
  20. Brunt AM, Haviland JS, Sydenham M, et al. Ten-year results of FAST: a randomized controlled trial of 5-fraction whole-breast radiotherapy for early breast cancer. J Clin Oncol. 2020;38(28):3261–3272. doi: 10.1200/JCO.19.02750
  21. Murray Brunt A, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020;395(10237):1613–1626. doi: 10.1016/S0140-6736(20)30932-6
  22. Meattini I, Becherini C, Boersma L, et al. European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer. Lancet Oncol. 2022;23(1):e21–e31. doi: 10.1016/S1470-2045(21)00539-8
  23. Bartelink H, Maingon P, Poortmans P, et al. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol. 2015;16(1):47–56. doi: 10.1016/S1470-2045(14)71156-8
  24. Romestaing P, Lehingue Y, Carrie C, et al. Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France. J Clin Oncol. 1997;15(3):963–968. doi: 10.1200/JCO.1997.15.3.963
  25. Vrieling C, van Werkhoven E, Maingon P, et al. Prognostic factors for local control in breast cancer after long-term follow-up in the eortc boost vs no boost trial: a randomized clinical trial. JAMA Oncol. 2017;3(1):42–48. doi: 10.1001/jamaoncol.2016.3031
  26. Vicini FA, Winter K, Freedman GM, et al. NRG RTOG 1005: a phase III trial of Hypo Fractionated whole breast irradiation with concurrent Boost vs. Conventional whole breast irradiation plus sequential Boost following lumpectomy for high risk early-stage breast cancer. Int J Radiat Oncol Bio Phys. 2022;114(3):S1. doi: 10.1016/j.ijrobp.2022.07.2320
  27. McHaffie DR, Patel RR, Adkison JB, et al. Outcomes after accelerated partial breast irradiation in patients with ASTRO consensus statement cautionary features. Int J Radiat Oncol Biol Phys. 2011;81(1):46–51. doi: 10.1016/j.ijrobp.2010.05.011
  28. Stull TS, Catherine Goodwin M, Gracely EJ, et al. A single-institution review of accelerated partial breast irradiation in patients considered “cautionary” by the American Society for Radiation Oncology. Ann Surg Oncol. 2012;19(2):553–559. doi: 10.1245/s10434-011-1941-7
  29. Pashtan IM, Recht A, Ancukiewicz M, et al. External beam accelerated partial-breast irradiation using 32 gy in 8 twice-daily fractions: 5-year results of a prospective study. Int J Radiat Oncol Biol Phys. 2012;84(3):e271–277. doi: 10.1016/j.ijrobp.2012.04.019
  30. Orecchia R, Veronesi U, Maisonneuve P, et al. Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-center, randomised, phase 3 equivalence trial. Lancet Oncol. 2021;22(5):597–608. doi: 10.1016/S1470-2045(21)00080-2
  31. Meattini I, Marrazzo L, Saieva C, et al. accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-florence trial. J Clin Oncol. 2020;38(35):4175–4183. doi: 10.1200/JCO.20.00650
  32. Whelan TJ, Julian JA, Berrang TS, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019;394(10215):2165–2172. doi: 10.1016/S0140-6736(19)32515-2
  33. Vicini FA, Cecchini RS, White JR, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. 2019;394(10215):2155–2164. doi: 10.1016/S0140-6736(19)32514-0
  34. Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307–316. doi: 10.1056/NEJMoa1415340
  35. Kim YB, Byun HK, Kim DY, et al. Effect of elective internal mammary node irradiation on disease-free survival in women with node-positive breast cancer: a randomized phase 3 clinical trial. JAMA Oncol. 2022;8(1):96–105. doi: 10.1001/jamaoncol.2021.6036
  36. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials. Lancet. 2023;402(10416):1991–2003. doi: 10.1016/S0140-6736(23)01082-6
  37. Wang J, Shi M, Ling R, et al. Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial. Radiother Oncol. 2011;100(2):200–204. doi: 10.1016/j.radonc.2011.07.007
  38. Haque W, Verma V, Farach A, et al. Postmastectomy radiation therapy for triple negative, node-negative breast cancer. Radiother Oncol. 2019;132:48–54. doi: 10.1016/j.radonc.2018.11.012
  39. Gillon P, Touati N, Breton-Callu C, et al. Factors predictive of loco regional recurrence following neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancer: An analysis of the EORTC 10994/BIG 1-00 study. Eur J Cancer. 2017;79:226–234. doi: 10.1016/j.ejca.2017.04.012
  40. Caudle AS, Yu TK, Tucker SL, et al. Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy. Breast Cancer Res. 2012;14(3):R83. doi: 10.1186/bcr3198
  41. Haffty BG, McCall LM, Ballman KV, et al. Impact of radiation on locoregional control in women with node-positive breast cancer treated with neoadjuvant chemotherapy and axillary lymph node dissection: results from ACOSOG Z1071 clinical trial. Int J Radiat Oncol Biol Phys. 2019;105(1):174–182. doi: 10.1016/j.ijrobp.2019.04.038
  42. Crown A, Gonen M, Le T, Morrow M. Does failure to achieve pathologic complete response with neoadjuvant chemotherapy identify node-negative patients who would benefit from postmastectomy radiation or regional nodal irradiation? Ann Surg Oncol. 2021;28(3):1328–1335. doi: 10.1245/s10434-020-09136-8
  43. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–172. doi: 10.1016/S0140-6736(13)62422-8
  44. Spring LM, Fell G, Arfe A, et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res. 2020;26(12):2838–2848. doi: 10.1158/1078-0432.CCR-19-3492
  45. Kayali M, Abi Jaoude J, Tfayli A, et al. Post-mastectomy radiation therapy in breast cancer patients with 1-3 positive lymph nodes: No one size fits all. Crit Rev Oncol Hematol. 2020;147:102880. doi: 10.1016/j.critrevonc.2020.102880
  46. Mamounas E, Bandos H, White J, et al. Loco-Regional Irradiation in patients with biopsyproven axillary node involvement at Presentation who become pathologically node-negative after Neoadjuvant Chemotherapy: primary outcomes of NRG Oncology/NSABP B-51/RTOG 1304.2023. Cancer Res. 2024;84(9_Suppl):GS02-07-GS02-07 doi: 10.1158/1538-7445.sabcs23-gs02-07
  47. Jamora K, Cruz-Lim EM, Cereno RE, et al. Hypofractionated radiotherapy in postmastectomy locally advanced breast cancer: an interim report on acute toxicities and dosimetry. Rep Pract Oncol Radiother. 2022;27(6):943–953. doi: 10.5603/RPOR.a2022.0102
  48. Wong JS, Uno H, Tramontano AC, et al. Hypofractionated vs conventionally fractionated postmastectomy radiation after implant-based reconstruction: a randomized clinical trial. JAMA Oncol. 2024;10(10):1370–1378. doi: 10.1001/jamaoncol.2024.2652
  49. Ahmed KA, Liveringhouse CL, Mills MN, et al. Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management. EBioMedicine. 2019;47:163–169. doi: 10.1016/j.ebiom.2019.08.019
  50. Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376(22):2147–2159. doi: 10.1056/NEJMoa1612645
  51. Woodward WA, Fang P, Arriaga L, et al. A phase 2 study of capecitabine and concomitant radiation in women with advanced breast cancer. Int J Radiat Oncol Biol Phys. 2017;99(4):777–783. doi: 10.1016/j.ijrobp.2017.04.030
  52. Schmid P, Cortes J, Dent R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386(6):556–567. doi: 10.1056/NEJMoa2112651
  53. Tison T, Loap P, Arnaud E, et al. Tolerance of concurrent adjuvant radiation therapy and pembrolizumab for triple negative breast cancer: real life experience. Adv Radiat Oncol. 2023;9(3):101384. doi: 10.1016/j.adro.2023.101384
  54. Voorwerk L, Slagter M, Horlings HM, et al. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019;25(6):920–928. doi: 10.1038/s41591-019-0432-4
  55. Geyer CE Jr, Garber JE, Gelber RD, et al. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022;33(12):1250–1268. doi: 10.1016/j.annonc.2022.09.159
  56. Jagsi R, Griffith KA, Bellon JR, et al. Concurrent veliparib with chest wall and nodal radiotherapy in patients with inflammatory or loco regionally recurrent breast cancer: The TBCRC 024 phase I multicenter study. J Clin Oncol. 2018;36(13):1317–1322. doi: 10.1200/JCO.2017.77.2665
  57. Loap P, Loirat D, Berger F, et al. concurrent olaparib and radiotherapy in patients with triple-negative breast cancer: the phase 1 olaparib and radiation therapy for triple-negative breast cancer trial. JAMA Oncol. 2022;8(12):1802–1808. doi: 10.1001/jamaoncol.2022.5074
  58. Chmura SJ. NRG-BR002: A phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer. J Clin Oncol. 2022;40 Supl 16:1007. doi: 10.1200/JCO.2022.40.16_suppl.1007
  59. Schaverien MV, Singh P, Smith BD, et al. Premastectomy radiotherapy and immediate breast reconstruction: a randomized clinical trial. JAMA Netw Open. 2024;7(4):e245217. doi: 10.1001/jamanetworkopen.2024.5217
  60. Meattini I, Francolini G, Di Cataldo V, et al. Preoperative robotic radiosurgery for early breast cancer: Results of the phase II ROCK trial (NCT03520894). Clin Transl Radiat Oncol. 2022;37:94–100. doi: 10.1016/j.ctro.2022.09.004
  61. Civil YA, Jonker LW, Groot Koerkamp MPM, et al. Preoperative partial breast irradiation in patients with low-risk breast cancer: a systematic review of literature. Ann Surg Oncol. 2023;30(6):3263–3279. doi: 10.1245/s10434-023-13233-9
  62. Kuerer HM, Smith BD, Krishnamurthy S, et al. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2022;23(12):1517–1524. doi: 10.1016/S1470-2045(22)00613-1

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