Toxicity and clinical outcomes of partial breast irradiation compared to whole breast irradiation for early-stage breast cancer: a systematic review and meta-analysis
There is uncertainty about outcomes differences between partial breast irradiation (PBI) and whole breast irradiation (WBI) for early-stage breast cancer.
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.
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).
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.
KeywordsPartial breast irradiation Whole breast irradiation Breast cancer Toxicity Local recurrence Survival
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.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 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
- 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.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
- 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
- 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.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.Hickey BE, Lehman M, Francis DP, See AM (2016) Partial breast irradiation for early breast cancer (review). Cochrane Database Syst Rev 7:CD007077Google Scholar
- 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.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
- 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
- 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.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
- 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.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.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.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
- 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
- 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
- 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.The IDEA Study (Individualized Decisions for Endocrine Therapy Alone). https://clinicaltrials.gov/ct2/show/NCT02400190. Accessed 15 May 2018
- 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.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.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