Current Trends and Challenges in Real-World Breast Cancer Adjuvant Radiotherapy: A Practical Review. New trends in adjuvant radiotherapy in BC
Main Article Content
Keywords
hypofractionated radiotherapy, neoadjuvant chemotherapy, oncoplastic surgery, reirradiation, adjuvant chemotherapy
Abstract
Background: The treatment of breast cancer (BC) remains a constant and rapidly evolving issue for multidisciplinary breast cancer teams. Considering the emerging understanding and advances in the biological course of this disease, new trends in radiotherapy fractionation, systemic therapies, and oncoplastic surgical techniques are revolutionizing adjuvant treatment approaches to BC. Novel challenges are questioning the integration of adjuvant radiotherapy (ART) into the real-world clinical setting.
Methods: PubMed literature search was conducted in order to extract data supporting the role of new trends in breast cancer adjuvant approach according to rising issues in the multidisciplinary team discussion such as sequencing with chemotherapy (CT) plus whole breast hypofractionated radiotherapy (HF-WBRT); the role of ART after neoadjuvant CT (NACT) followed by breast conservative surgery (BCS) in early BC achieving pathological complete remission (pCR); and the integration of ART in immediate autologous breast oncoplastic reconstruction after mastectomy (a-IBR). Furthermore, there are still several concerns about toxicity with adjuvant trastuzumab emtansine (T-DM1) or breast re-irradiation after BCS relapse in long-term survivors refusing mastectomy.
Results: Among 40 hits, only 12 studies answered to these issues. Many of them were retrospective studies. Less than 500 patients met the criteria for these issues and several conclusions were found exhaustive.
Conclusion: Few issues seem to have literature solutions, while there are still open questions in regard to these new trends. Novel strategies through prospective or randomized studies and new consensus guidelines are required.
References
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3. Espenel S, Chargari C, Blanchard P, Bockel S, Morel D, Rivera S, et al. Practice changing data and emerging concepts from recent radiation therapy randomised clinical trials. Eur J Cancer 2022; 171:242-58. doi: 10.1016/j.ejca.2022.04.038
4. START Trialists' Group, Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, et al. The UK standardisation of breast radiotherapy (START) trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol 2008; 9:331–341. doi:10.1016/S1470-2045(08)70077-9.
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6. Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, 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.
7. Asselain B, Barlow W, Bartlett J, Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27–39. doi: 10.1016/S1470-2045(17)30777- 5
8. von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628. doi: 10.1056/NEJMoa1814017.
9. Panchal H, Matros E. Current Trends in Post-Mastectomy Breast Reconstruction. Plast Reconstr Surg. 2017; 140(5): 7S–13S. doi:10.1097/PRS.0000000000003941
10. Brewster AM, Hortobagyi GN, Broglio KR, Kau SW, Santa-Maria CA, Arun B, et al. Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst. 2008; 100(16):1179-183. doi: 10.1093/jnci/djn233
11. Freedman GM, Fowble BL. Local recurrence after mastectomy or breast-conserving surgery and radiation. Oncology (Williston Park). 2000; 14(11):1561-1581; discussion 1581-1562, 1582-1564.
12. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108. doi:10.3322/caac.21262
13. Al-Hilli Z, Thomsen KM, Habermann EB, Jakub JW, Boughey JC. Reoperation for complications after lumpectomy and mastectomy for breast cancer from the 2012 National Surgical Quality Improvement Program (ACS-NSQIP). Ann Surg Oncol. 2015; 22(Suppl 3):S459–S69. doi: 10.1245/s10434-015-4741-7
14. Aerts L, Christiaens MR, Enzlin P, Neven P, Amant F. Sexual functioning in women after mastectomy versus breast conserving therapy for early-stage breast cancer: a prospective controlled study. Breast. 2014; 23(5):629–36. doi: 10.1016/j.breast.2014.06.012
15. Moran MS, Truong PT. Hypofractionated radiation treatment of breast cancer: The time is now. Breast J. 2020;00:1–8. doi: 10.1111/tbj.13724
16. Gupta A, Ohiri N, Haffty BG. Hypofractionated radiation treatment in the management of breast cancer. Expert Rev Anticancer Ther. 2018; 18(8): 793–803. doi:10.1080/14737140.2018.1489245
17. Pondè NF, Zarvadas D, Piccart M. Progress in adjuvant systemic therapy for breast cancer- Nat Rev Clin Oncol. 2019 Jan; 16(1):27-44. doi: 10.1038/s41571-018-0089-9
18. Syed YY. Oncotype DX Breast Recurrence Score ®: A Review of its Use in Early-Stage Breast Cancer. Mol Diagn Ther. 2020 Oct;24(5):621-632. doi: 10.1007/s40291-020-00482-7
19. Almstedt K, Mendoza S, Otto M, Battista MJ, Steetskamp J, Heimes AS, et al. EndoPredict® in early hormone receptor-positive, HER2-negative breast cancer. Breast Cancer Res Treat. 2020 Jul;182(1):137-146. doi: 10.1007/s10549-020-05688-1
20. Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, et al. The sequencing of chemotherapy and radiation therapy after conservative surgery for early stage breast cancer. N Engl J Med .1996; 334:1356- 61, doi: 10.1056/NEJM199605233342102
21. Bellon JR, Come SE, Gelman RS, Henderson IC, Shulman LN, Silver BJ, et al. Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial. J Clin Oncol. 2005 Mar 20;23(9):1934-40. doi: 10.1200/JCO.2005.04.032
22. Belletti B, Vaidya JS, D'Andrea S, Entschladen F, Roncadin M, Lovat F, et al. Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res. 2008 Mar 1;14(5):1325-32. doi: 10.1158/1078-0432.CCR-07-4453.
23. Formenti SC, Demaria S. Local control by radiotherapy: is that all there is? Breast Cancer Research 2008, 10:215-22. doi:10.1186/bcr2160.
24. Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E. Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res 1989; 49: 1996–2001
25. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164–72. doi: 10.1016/S0140-6736(13)62422-8
26. von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2013; 31: 3623–30. doi: 10.1200/JCO.2012.45.0940.
27. Cortazar P, Geyer CE jr. Pathological complete response in neaoadjuvant treatment of breast cancer. Ann Surg Oncol. 2015 May;22(5):1441-6. doi: 10.1245/s10434-015-4404-8
28. Houssami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 2012; 48(18): 3342–54. doi: 10.1016/j.ejca.2012.05.023
29. Denkert C, Liedtke C, Tutt A, von Minckwitz G. Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet. 2017 Jun 17;389(10087):2430–42. doi: 10.1016/S0140-6736(16)32454-0.
30. McGuire SE, Gonzalez-Angulo AM, Huang EH, Tucker SL, Kau SW, Yu TK, et al. Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):1004-9. doi: 10.1016/j.ijrobp.2007.01.023.
31. Mamounas EP, Bandos H, White JR, Julian TB, Khan AJ, Shaitelman SF, et al. NRG Oncology/NSABP B-51/RTOG 1304: Phase III trial to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to whole breast RT post breast-conserving surgery (BCS) reduces invasive breast cancer recurrence-free interval (IBCR-FI) in patients (pts) with pathologically positive axillary (PPAx) nodes who are ypN0 after neoadjuvant chemotherapy (NC). Journal of Clinical Oncology 2019. doi: 10.1200/JCO.2019.37.15_suppl.TPS600.
32. Boughey J, Haffty B, Buchholz T, Symmans WF, Hunt K, Armer J, et al. Alliance A011202: A Randomized Phase III Trial Comparing Axillary Lymph Node Dissection to Axillary Radiation in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Receiving Neoadjuvant Chemotherapy. Available from: https://www.allianceforclinicaltrialsinoncology.org/main/cmsfile?cmsPath=/Public/Annual%20Meeting/files/A011202-Boughey-May2019.pdf
33. Mandish S, Gaskins JT, Yusuf MB, Amer YM, Eldredge-Hindy H. The effect of omission of adjuvant radiotherapy after neoadjuvant chemotherapy and breast conserving surgery with a pathologic complete response. Acta Oncol 2020; 59(10): 1210-17. doi: 10.1080/0284186X.2020.1797161
34. von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019; 380: 617-28. doi: 10.1056/NEJMoa1814017
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Lazzari G, Solazzo AP, Benevento I, Montagna A, Rago L, Castaldo G, Silvano G. Current Trends and Challenges in Real-World Breast Cancer Adjuvant Radiotherapy: A Practical Review. : New trends in adjuvant radiotherapy in BC. Arch Breast Cancer [Internet]. 2022 Dec. 27 [cited 2023 Mar. 29];10(1):6-14. Available from: https://www.archbreastcancer.com/index.php/abc/article/view/643
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Author Biographies
Angela Pia Solazzo, Radiation Oncology Unit, IRCCS-CROB, Rionero in Vulture (PZ), Italy
MD Radiation Oncologist
Ilaria Benevento, Radiation Oncology Unit, IRCCS-CROB, Rionero in Vulture (PZ), Italy
MD Radiation Oncologist
Antonietta Montagna, Radiation Oncology Unit -IRCCS CROB Rionero in Vulture
MD Radiation Oncologist
Luciana Rago, Radiation Oncology Unit -IRCCS CROB Rionero in Vulture, Italy
MD Radiation Oncologist
Giovanni Castaldo, Radiation Oncology Unit -IRCCS CROB Rionero in Vulture
MD Radiation Oncologist
Giovanni Silvano, Emicenter Casoria -Napoli
MD Radiation Oncologist -Radiotherapy Unit
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