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Toxicity and clinical outcomes of partial breast irradiation compared to whole breast irradiation for early-stage breast cancer: a systematic review and meta-analysis

  • Yasmin Korzets
  • Anthony Fyles
  • Daniel Shepshelovich
  • Eitan Amir
  • Hadar GoldvaserEmail author
Review

Abstract

Purpose

There is uncertainty about outcomes differences between partial breast irradiation (PBI) and whole breast irradiation (WBI) for early-stage breast cancer.

Methods

Prospective randomized trials comparing adjuvant PBI to WBI in early-stage invasive breast cancer were identified using PubMed. Odds ratios (OR), 95% confidence intervals and absolute risks were computed for pre-specified efficacy and toxicity outcomes including cosmesis. Subgroup analysis evaluated the effect of PBI modality (external beam radiation treatment [EBRT], intraoperative radiation treatment [IORT] or brachytherapy) on efficacy. Meta-regression analysis explored the influence of median follow-up, patient and tumor characteristics on results.

Results

Nine trials comprising 14514 patients were included. While PBI was associated with increased odds of local recurrence compared to WBI (OR 1.69, P < 0.001), it was associated with reduced odds of death without breast cancer recurrence (OR 0.55, P < 0.001) and with improvement in overall survival (OS) that approached, but did not meet statistical significance (OR 0.84, P = 0.06). Subgroup analysis for PBI modality showed significant differences in the odds of local recurrence, based on method of PBI with EBRT showing the lowest magnitude of inferiority. Nodal involvement was associated with higher local recurrence risk, while larger tumors were associated with lesser improvement in death without breast cancer recurrence and OS. PBI was associated with higher odds of fat necrosis (OR 1.72, P = 0.002). Worse cosmetic outcome with PBI approached statistical significance (OR 1.23, P = 0.06).

Conclusions

Compared to WBI, PBI is associated with higher odds for local recurrence and toxicity, but less death without breast cancer recurrence. The balance between benefit and risk of PBI appears optimal for women with smaller hormone receptor positive tumors, without nodal involvement and treated with EBRT.

Keywords

Partial breast irradiation Whole breast irradiation Breast cancer Toxicity Local recurrence Survival 

Notes

Compliance with ethical standards

Conflict of interest

Yasmin Korzets, Anthony Fyles, and Daniel Shepshelovich declare that they have no conflict of interest. Eitan Amir declares that he has received fees from Genentech/Roche for Expert Testimony and from Apobiologix for Advisory Boards. These fees were outside of the submitted work. Hadar Goldvaser declares honorarium payment from Roche for invited speaker. These fees were outside of the submitted work.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10549_2019_5209_MOESM1_ESM.docx (39 kb)
Supplementary material 1 (DOCX 38 KB)

References

  1. 1.
    Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M et al (2011) 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 378(9804):1707–1716CrossRefGoogle Scholar
  2. 2.
    Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D et al (2013) Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368(11):987–998CrossRefGoogle Scholar
  3. 3.
    Taylor C, Correa C, Duane FK, Aznar MC, Anderson SJ, Bergh J et al (2017) Estimating the risks for lung cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. J Clin Oncol 35(15):1641–1649CrossRefGoogle Scholar
  4. 4.
    Henson KE, McGale P, Taylor C, Darby SC (2013) Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer. Br J Cancer 108(1):179–182CrossRefGoogle Scholar
  5. 5.
    Veronesi U, Marubini E, Mariani L, Galimberti V, Luini A, Veronesi P et al (2001) Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol 12(7):997–1003CrossRefGoogle Scholar
  6. 6.
    Liljegren G, Holmberg L, Bergh J, Lindgren A, Tabár L, Nordgren H et al (1999) 10-year results after sector resection with or without post-operative radiotherapy for stage I breast cancer: a randomized trial. J Clin Oncol 17(8):2326–2333CrossRefGoogle Scholar
  7. 7.
    Smith TE, Lee D, Turner BC, Carter D, Haffty BG (2000) True recurrence vs. new primary ipsilateral breast tumor relapse: an analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management. Int J Radiat Oncol Biol Phys 48(5):1281–1289CrossRefGoogle Scholar
  8. 8.
    Stewart AJ, O’Farrell DA, Cormack RA, Hansen JL, Khan AJ, Mutyala S et al (2008) Dose volume histogram analysis of normal structures associated with accelerated partial breast irradiation delivered by high dose rate brachytherapy and comparison with whole breast external beam radiotherapy fields. Radiat Oncol 3:39CrossRefGoogle Scholar
  9. 9.
    Gale AA, Jain AK, Vallow LA, Serago CF, Buskirk SJ, Heckman MG (2009) Cardiac dose evaluation for 3-dimensional conformal partial breast irradiation compared with whole breast irradiation. J Appl Clin Med Phys 10(1):2868CrossRefGoogle Scholar
  10. 10.
    Polgár C, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T et al (2017) Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole- breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial. Lancet Oncol 18(2):259–268CrossRefGoogle Scholar
  11. 11.
    Polgár C, Fodor J, Major T, Sulyok Z, Kásler M (2013) Breast-conserving therapy with partial or whole breast irradiation: ten-year results of the Budapest randomized trial. Radiother Oncol 108(2):197–202CrossRefGoogle Scholar
  12. 12.
    Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C et al (2013) Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol 14(13):1269–1277CrossRefGoogle Scholar
  13. 13.
    Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M et al (2014) Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet 383(9917):603–613CrossRefGoogle Scholar
  14. 14.
    Liu G, Dong Z, Huang B, Liu Y, Tang Y, Li Q et al (2017) Efficacy and safety of accelerated partial breast irradiation: a meta-analysis of published randomized studies. Oncotarget 8(35):59581–59591Google Scholar
  15. 15.
    Hickey BE, Lehman M, Francis DP, See AM (2016) Partial breast irradiation for early breast cancer (review). Cochrane Database Syst Rev 7:CD007077Google Scholar
  16. 16.
    Huo J, Giordano SH, Smith BD et al (2016) Contemporary toxicity profile of breast brachytherapy versus external beam radiation after lumpectomy for breast cancer. Int J Radiat Oncol Biol Phys 94:709–718CrossRefGoogle Scholar
  17. 17.
    Vaidya JS, Bulsara M, Wenz F, Coombs N, Singer J, Ebbs S et al (2016) Reduced mortality with partial-breast irradiation for early breast cancer: a meta-analysis of randomized trials. Int J Radiat Oncol Biol Phys 96(2):259–265CrossRefGoogle Scholar
  18. 18.
    Correa C, Harris EE, Leonardi MC. Smith BD, Taghian AG, Thompson AM et al (2017) Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol 7(2):73–79CrossRefGoogle Scholar
  19. 19.
    Polgár C, Van Limbergen E, Pötter R, Kovács G, Polo A, Lyczek J et al (2010) Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: recommendations of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009). Radiother Oncol 94(3):264–273CrossRefGoogle Scholar
  20. 20.
    Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A et al (2017) Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet 390(10099):1048–1060CrossRefGoogle Scholar
  21. 21.
    Sweeting MJ, Sutton AJ, Lambert PC (2004) What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 23(9):1351–1375CrossRefGoogle Scholar
  22. 22.
    Higgins JPT, Deeks JJ, Altman DG (2011) Meta-analysis of rare events. In: Higgins JPT, Green S (eds) Cochrane handbook for systematic reviews of interventions (version 5.1.0). The Cochrane Collaboration, LondonGoogle Scholar
  23. 23.
    Deeks JJ (2001) Systematic reviews in health care: Systematic reviews of evaluations of diagnostic and screening tests. Br Med J 323(7305):157–162CrossRefGoogle Scholar
  24. 24.
    Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T et al (2016) 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet 387(10015):229–238CrossRefGoogle Scholar
  25. 25.
    Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C et al (2015) Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer 51(4):451–463CrossRefGoogle Scholar
  26. 26.
    Rodriguez N, Sanz X, Dengra J, Foro P, Membrive I, Reig A et al (2013) Five-year outcomes, cosmesis, and toxicity with 3-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys 87(5):1051–1057CrossRefGoogle Scholar
  27. 27.
    Olivotto IA, Whelan TJ, Parpia S, Kim DH, Berrang T, Truong PT et al (2013) Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol 31(32):4038–4045CrossRefGoogle Scholar
  28. 28.
    Whelan T, Julian J, Levine M, Berrang T, Kim D-H, Gu CS et al (2018) RAPID: a randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT). In: San Antonio Breast cancer symposium, GS4-03Google Scholar
  29. 29.
    Vicini FA, Cecchini RS, White JR, Julian TB, Arthur DW, Rabinovitch RA et al (2018) Primary results of NSABP B-39/RTOG 0413 (NRG Oncology): a randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer. In: San Antonio breast cancer symposium, GS4-04Google Scholar
  30. 30.
    Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Saunders C et al (2016) An international randomized controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial). Health Technol Assess 20:1–188CrossRefGoogle Scholar
  31. 31.
    Peterson D, Truong PT, Parpia S, Olivotto IA, Berrang T, Kim DH et al (2015) Predictors of adverse cosmetic outcome in the RAPID trial: an exploratory analysis. Int J Radiat Oncol Biol Phys 91(5):968–976CrossRefGoogle Scholar
  32. 32.
    Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V et al (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106CrossRefGoogle Scholar
  33. 33.
    Cuzick J, Stewart H, Rutqvist L, Houghton J, Edwards R, Redmond C et al (1994) Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol 12(3):447–453CrossRefGoogle Scholar
  34. 34.
    Drost L, Yee C, Lam H, Zhang L, Wronski M, McCann C et al (2018) A systematic review of heart dose in breast radiotherapy. Clin Breast Cancer 18:e819–e824CrossRefGoogle Scholar
  35. 35.
    Taylor CW, Wang Z, Macaulay E, Jagsi R, Duane F, Darby SC (2015) Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003–2013. Int J Radiat Oncol Biol Phys 93(4):845–853CrossRefGoogle Scholar
  36. 36.
    Kirby AM, Evans PM, Donovan EM, Convery HM, Haviland JS, Yarnold JR (2010) Prone versus supine positioning for whole and partial-breast radiotherapy: a comparison of non-target tissue dosimetry. Radiother Oncol 96(2):178–184CrossRefGoogle Scholar
  37. 37.
    Burt LM, Ying J, Poppe MM, Suneja G, Gaffney DK (2017) Risk of secondary malignancies after radiation therapy for breast cancer: comprehensive results. Breast 35:122–129CrossRefGoogle Scholar
  38. 38.
    De bruin ML, Sparidans J, van’t Veer MB, Noordijk EM, Louwman MW, Zijlstra JM et al (2009) Breast cancer risk in female survivors of Hodgkin’s lymphoma: lower risk after smaller radiation volumes. J Clin Oncol 27(26):4239–4246CrossRefGoogle Scholar
  39. 39.
    Cardoso F, van’t Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S et al (2016) 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 375(8):717–729CrossRefGoogle Scholar
  40. 40.
    Park YH, Lee SJ, Cho EY, Choi YL, Lee JE, Nam SJ et al (2011) Clinical relevance of TNM staging system according to breast cancer subtypes. Ann Oncol 22(7):1554–1560CrossRefGoogle Scholar
  41. 41.
    Harris LN, Ismalla N, McShane LM, Andre F, Collyar DE, Gonzalez-Angulo AM et al (2016) Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 34(10):1134–1150CrossRefGoogle Scholar
  42. 42.
    Horton JK, Jagsi R, Woodward WA, Ho A (2018) Breast cancer biology: clinical implications for breast radiation therapy. Int J Radiat Oncol Biol Phys 100(1):23–37CrossRefGoogle Scholar
  43. 43.
    Mamounas EP, Liu Q, Paik S, Baehner FL, Tang G, Jeong JH et al (2017) 21 Gene recurrence score and locoregional recurrence in node-positive/ER-positive breast cancer treated with chemo-endocrine therapy.J Natl Cancer Inst 109(4)Google Scholar
  44. 44.
    Bouganim N, Tsvetkova E, Clemons M, Amir E (2013) Evolution of sites of recurrence after early breast cancer over the last 20 years: implications for patient care and future research. Breast Cancer Res Treat 139(2):603–606CrossRefGoogle Scholar
  45. 45.
    Prospective cohort study evaluating risk of local recurrence following breast conserving surgery and endocrine therapy in Low Risk Luminal A Breast Cancer (LUMINA). https://clinicaltrials.gov/ct2/show/NCT01791829. Accessed 15 May 2018
  46. 46.
    The IDEA Study (Individualized Decisions for Endocrine Therapy Alone). https://clinicaltrials.gov/ct2/show/NCT02400190. Accessed 15 May 2018
  47. 47.
    The PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): a phase II study of breast-conserving surgery without adjuvant radiotherapy for favorable-risk breast cancer. https://clinicaltrials.gov/ct2/show/NCT02653755. Accessed 15 May 2018
  48. 48.
    Chesney TR, Yin JX, Rajaee N, Tricco AC, Fyles AW, Acuna SA et al (2017) Tamoxifen with radiotherapy compared with Tamoxifen alone in elderly women with early-stage breast cancer treated with breast conserving surgery: a systematic review and meta-analysis. Radiother Oncol 123(1):1–9CrossRefGoogle Scholar
  49. 49.
    Manyam BV, Tendulkar R, Cherian S, Vicini F, Badiyan SN, Shah C (2018) Evaluating candidacy for hypofractionated radiation therapy, accelerated partial breast irradiation, and endocrine therapy after breast conserving surgery: a Surveillance Epidemiology and End Results (SEER) analysis. Am J Clin Oncol 41(6):526–531CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiation Oncology, Princess Margaret Cancer CentreUniversity of TorontoTorontoCanada
  2. 2.Davidoff Cancer Center, Beilinson HospitalRabin Medical CenterPetach TikvaIsrael
  3. 3.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  4. 4.Division of Medical Oncology, Princess Margaret Cancer CentreUniversity of TorontoTorontoCanada

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