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Current Breast Cancer Reports
Erschienen in:

11.08.2023

Pre-operative Radiation and Immunotherapy in the Treatment of Non-metastatic Breast Cancer

verfasst von: Pooja Karukonda, Alice Y. Ho, Susan McDuff

Erschienen in: Current Breast Cancer Reports | Ausgabe 3/2023

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Abstract

Purpose of Review

To discuss the rationale and latest strategies for combining pre-operative radiation therapy (pre-op RT) and immunotherapy (IO) in the treatment of non-metastatic breast cancer.

Recent Findings

IO has recently been incorporated into the standard-of-care treatment for patients with stage II–III triple-negative breast cancer. Other subtypes of breast cancer have notably been excluded from most major IO trials due to their perceived lack of immunogenicity, though oncologic outcomes for all high-risk patients warrant further improvement. Early-phase clinical trials have demonstrated the feasibility of pre-op RT. There is a sound pre-clinical basis for the combination of pre-op RT and IO to induce robust local and systemic anti-tumor immunomodulation in patients with all types of breast cancer.

Summary

There is emerging interest in utilizing pre-op RT to prime the anti-tumor immune response and potentially promote an abscopal effect when combined with IO. Trials investigating various combinations of pre-op RT and IO are underway.
Literatur
1.
2.
Pfeiffer RM, et al. Proportion of U.S. trends in breast cancer incidence attributable to long-term changes in risk factor distributions. Cancer Epidemiol Biomarkers Prev. 2018;27(10):1214–22.CrossRefPubMedPubMedCentral
3.
4.
Pelekanou V, et al. Tumor-infiltrating lymphocytes and PD-L1 expression in pre- and posttreatment breast cancers in the SWOG S0800 phase II neoadjuvant chemotherapy trial. Mol Cancer Ther. 2018;17(6):1324–31.CrossRefPubMedPubMedCentral
5.
Tarantino P, et al. Immunotherapy addition to neoadjuvant chemotherapy for early triple negative breast cancer: a systematic review and meta-analysis of randomized clinical trials. Crit Rev Oncol Hematol. 2021;159:103223.CrossRefPubMed
6.
Arvold ND, et al. Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol. 2011;29(29):3885–91.CrossRefPubMedPubMedCentral
7.
Horton JK, et al. Breast cancer biology: clinical implications for breast radiation therapy. Int J Radiat Oncol Biol Phys. 2018;100(1):23–37.CrossRefPubMed
8.
Segovia-Mendoza M, Morales-Montor J. Immune tumor microenvironment in breast cancer and the participation of estrogen and its receptors in cancer physiopathology. Front Immunol. 2019;10:348.CrossRefPubMedPubMedCentral
9.
10.
Goff SL, Danforth DN. The role of immune cells in breast tissue and immunotherapy for the treatment of breast cancer. Clin Breast Cancer. 2021;21(1):e63–73.CrossRefPubMed
11.
Schmid P, et al. Atezolizumab and Nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–21.CrossRefPubMed
12.
•• Cortes J, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28. This randomized trial of pembrolizumab plus chemotherapy vs placebo plus chemotherapy demonstrated a significant improvement in progression-free survival with the addition of pembrolizumab, establishing its role in standard of care management of patients with metastatic triple negative breast cancer with high surface PD-L1 expression.CrossRefPubMed
13.
Jacob SL, Huppert LA, Rugo HS. Role of immunotherapy in breast cancer. Oncol Pract. 2023;0(0):OP.22.00483.
14.
•• Schmid P, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810–21. This phase III trial in which patients with treatment-naïve stage II-III TNBC were randomized to receive pembrolizumab or placebo plus standard chemotherapeutic agents in the neoadjuvant setting, with continued pembrolizumab in the adjuvant setting, demonstrated significantly improved pCR with the addition of pembrolizumab.CrossRefPubMed
15.
•• Schmid P, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386(6):556–67. This phase III trial in which patients with treatment-naïve stage II-III TNBC were randomized to receive pembrolizumab or placebo plus standard chemotherapeutic agents in the neoadjuvant setting, with continued pembrolizumab in the adjuvant setting, demonstrated significantly improved three-year event-free survival with the addition of pembrolizumab. Pembrolizumab has since been approved by the FDA and incorporated into the standard of care for this patient population with high-risk early-stage TNBC.CrossRefPubMed
16.
• Mittendorf EA, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100. This double-blind phase III study randomized patients with previously untreated stage II-III TNBC to receive chemotherapy plus atezolizumab vs placebo and demonstrated significant improvement in pCR with an acceptable safety profile with the addition of atezolizumab.CrossRefPubMed
17.
•• Nanda R, et al. Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 2020;6(5):676–84. The ongoing phase II I-SPY2 trial is studying the addition of pembrolizumab to neoadjuvant chemotherapy and interestingly demonstrated improvement in pCR rates not only in patients with TNBC, but also in those with high-risk HR positive/HER2 negative breast cancers receiving pembrolizumab, indicating that even breast cancer subtypes that are more immunologically quiescent can potentially benefit from IO.CrossRefPubMed
18.
Loibl S, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30(8):1279–88.CrossRefPubMed
19.
Loibl S, et al. Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC). J Clin Oncol. 2021;39(15_suppl):506–506.CrossRef
20.
Cardoso F, et al. KEYNOTE-756: randomized, double-blind, phase 3 study of pembrolizumab vs placebo combined with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk, early-stage estrogen receptor–positive, human epidermal growth factor receptor 2–negative (ER+/HER2−) breast cancer. J Clin Oncol. 2019;37(15_suppl):TPS601–TPS601.CrossRef
21.
Karn T, et al. Tumor mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo. Ann Oncol. 2020;31(9):1216–22.CrossRefPubMed
22.
Zhou Z, Li M. Evaluation of BRCA1 and BRCA2 as indicators of response to immune checkpoint inhibitors. JAMA Netw Open. 2021;4(5):e217728–e217728.CrossRefPubMedPubMedCentral
23.
•• Tarantino P, et al. Immunotherapy for early triple negative breast cancer: research agenda for the next decade. NPJ Breast Cancer. 2022;8(1):23. This multi-center, phase III, non-inferiority trial randomized patients with pT1–3, pN0–1, M0 breast carcinoma after breast conservation surgery or mastectomy to 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall, and demonstrated non-inferiority of 26 Gy in five fractions to 40 Gy in 15 fractions in terms of local tumor control and toxicity, upon five-year follow up.CrossRefPubMedPubMedCentral
24.
Early Breast Cancer Trialists’ Collaborative Group 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): 1707–16
25.
•• Murray Brunt A, 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):1613–26. This phase III trial randomized patients with pT1-2 pN0 breast carcinoma to 50 Gy in 25 fractions (5 weeks) or 30 or 28.5 Gy in five once-weekly fractions and demonstrated no significant difference in normal tissue effects between 50 Gy in 25 fractions and 28.5 Gy in five once-weekly fractions, upon 10-year follow up.CrossRefPubMedPubMedCentral
26.
Haviland JS, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013;14(11):1086–94.CrossRefPubMed
27.
Brunt AM, 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):3261–72.CrossRefPubMedPubMedCentral
28.
Koenig JL, et al. Use of preoperative radiation therapy in early-stage and locally advanced breast cancer. Cureus. 2019;11(9):e5748.PubMedPubMedCentral
29.
Rahimi A, et al. Preliminary results of multi-institutional phase 1 dose escalation trial using single-fraction stereotactic partial breast irradiation for early stage breast cancer. Int J Radiat Oncol Biol Phys. 2022;112(3):663–70.CrossRefPubMed
30.
Palta M, et al. Preoperative single fraction partial breast radiotherapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2012;82(1):37–42.CrossRefPubMed
31.
Horton JK, et al. Preoperative single-fraction partial breast radiation therapy: a novel phase 1, dose-escalation protocol with radiation response biomarkers. Int J Radiat Oncol Biol Phys. 2015;92(4):846–55.CrossRefPubMedPubMedCentral
32.
Blitzblau RC, et al. A phase 1 trial of preoperative partial breast radiation therapy: patient selection, target delineation, and dose delivery. Pract Radiat Oncol. 2015;5(5):e513–20.CrossRefPubMedPubMedCentral
33.
Guidolin K, et al. Stereotactic image-guided neoadjuvant ablative single-dose radiation, then lumpectomy, for early breast cancer: the SIGNAL prospective single-arm trial of single-dose radiation therapy. Curr Oncol. 2019;26(3):e334–40.CrossRefPubMedPubMedCentral
34.
• Vasmel JE, et al. Tumor response after neoadjuvant magnetic resonance guided single ablative dose partial breast irradiation. Int J Radiat Oncol Biol Phys. 2020;106(4):821–9. This multi-center prospective trial investigated the utility of single-fraction pre-op partial breast SBRT in patients with low-risk breast cancer, and reported favorable results, with pCR in 15 of 36 patients (42%), and acceptable associated toxicity rates.CrossRefPubMed
35.
Liveringhouse CL, Mills MN, Ahmed KA, Washington IR, Lee MC, Khakpour N, Laronga C, Czerniecki B, Soliman H, Weinfurtner RJ, Rosa M, Kim Y, Stringfield O, Abdalah M, Diaz R, Montejo M. Phase 2 study of preoperative SABR for early-stage breast cancer: introduction of a novel form of accelerated partial breast radiation therapy. Int J Radiat Oncol Biol Phys. 2023;116(3):611–6.CrossRefPubMed
36.
37.
Craig DJ, et al. The abscopal effect of radiation therapy. Future Oncol. 2021;17(13):1683–94.CrossRefPubMed
38.
39.
40.
De Caluwe A, et al. Neo-CheckRay: radiation therapy and adenosine pathway blockade to increase benefit of immuno-chemotherapy in early stage luminal B breast cancer, a randomized phase II trial. BMC Cancer. 2021;21(1):899.CrossRefPubMedPubMedCentral
41.
•• Ho AY, et al. Optimizing radiation therapy to boost systemic immune responses in breast cancer: a critical review for breast radiation oncologists. Int J Radiat Oncol Biol Phys. 2020;108(1):227–41. This comprehensive review article highlights the merits and challenges associated with combining RT and IO in the treatment of breast cancer, with an emphasis on design of meaningful clinical trials in order to further investigation.CrossRefPubMedPubMedCentral
Metadaten
Titel
Pre-operative Radiation and Immunotherapy in the Treatment of Non-metastatic Breast Cancer
verfasst von
Pooja Karukonda
Alice Y. Ho
Susan McDuff
Publikationsdatum
11.08.2023
Verlag
Springer US
Erschienen in
Current Breast Cancer Reports / Ausgabe 3/2023
Print ISSN: 1943-4588
Elektronische ISSN: 1943-4596
DOI
https://doi.org/10.1007/s12609-023-00507-0

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